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Advances in research on the intestinal microbiota in the mechanism and prevention of colorectal cancer (Review)

  • Authors:
    • Weitong Sun
    • Shize Ma
    • Dongdong Meng
    • Chaoxing Wang
    • Jinbo Zhang

  • View Affiliations

  • Published online on: March 19, 2025     https://doi.org/10.3892/mmr.2025.13498
  • Article Number: 133

  • Copyright: © Sun et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The intestinal microbiota represents a diverse population that serves a key role in colorectal cancer (CRC) and its treatment outcomes. Advancements in sequencing have revealed notable shifts in microbial composition and diversity among individuals with CRC. Concurrently, animal models have elucidated the involvement of specific microbes such as Lactobacillus fragilis, Escherichia coli and Fusobacterium nucleatum in the progression of CRC. The present review aimed to highlight contributions of intestinal microbiota to the pathogenesis of CRC, the effects of traditional treatments on intestinal microbiota and the potential for microbiota modulation as a therapeutic strategy for CRC.

Introduction

Colorectal cancer (CRC) is the third most common cancer worldwide, accounting for ~10% of all tumour-related deaths, and its multifaceted etiology involves genetic and environmental factors (1). The majority of CRC cases (90%) develop sporadically over time, with multiple risk factors contributing to its onset (2,3). Notably, environmental factors such as pro-inflammatory environments induce changes in the composition and structure of intestinal microbiota (4,5).

The human intestinal microbiota is key for numerous functions, including energy acquisition, intestinal epithelial repair, defense against pathogens and immune regulation (6). Certain probiotics and their metabolites exhibit anti-CRC effects by utilizing short-chain fatty acids (SCFAs) to modulate CD8+ T cell activity (7). In CRC treatment, probiotics enhance the effectiveness of radiotherapy and other therapeutic modalities, mitigate side effects and improve therapeutic outcomes (8). In a recent study, the probiotic strain E.coli Nissle 1917 (EcN) demonstrated the ability to enhance the drug efficacy and overcome resistance to prodrugs, including CB1954 and fludarabine phosphate. When administered in combination with these prodrugs to BALB/c mice with CT26 tumors, EcN exhibits considerable antitumor effects (9). Conversely, disruption of intestinal microbiota equilibrium disrupts normal physiological functions and contributes to the onset of diseases such as inflammatory bowel disease and CRC (10). The gut microbiota produces pathogenic metabolites that trigger the release of genotoxic disease-causing agents, potentially fostering the development of CRC (11). Recent findings have revealed decreased diversity and abundance of bacterial populations in fecal samples and intestinal mucosa from patients with CRC compared with those of healthy individuals (12,13). Notably, alterations in specific bacterial populations within CRC may affect the mucosal immune response, potentially leading to an increase in pro-inflammatory pathogenic bacteria and a decrease in probiotics. This microbial imbalance, known as dysbiosis, contributes to the development of CRC (14,15). Therefore, investigating the oncogenic roles of detrimental bacteria provides a foundation for use of intestinal microbiota and their metabolites as potential biomarkers for CRC. Intestinal microbiota hold promise as a tool for screening, diagnosing, treating and predicting outcomes in CRC. Furthermore, prior research has emphasized the potential of modulating the intestinal microbiota in conjunction with conventional therapeutic strategies to manage CRC, highlighting microbiota research as a potential avenue for prevention and therapy for patients with CRC (16,17).

Microbial mechanisms in CRC

Mechanisms through which the intestinal microbiota contribute to the onset of CRC include inflammatory pathways, intestinal microbial metabolic products, gene toxins and virulence factors, oxidative stress and regulation of antioxidant defenses (Fig. 1).

Inflammatory pathways

Chronic inflammation poses a key risk to CRC (18). This persistent inflammatory state may lead to mutations, suppress apoptosis and promote angiogenesis as well as cellular proliferation, thus increasing the risk of CRC (19). An imbalance in the intestinal microbiota, favoring opportunistic pathogens, can enhance mucosal permeability, facilitate bacterial translocation and activate both innate and adaptive immune responses, thereby perpetuating chronic inflammation (20).

The chronic inflammatory response within the colorectal region, mediated by the intestinal microbiota, recruits inflammatory cells and triggers the release of multiple mediators of inflammation such as IL-6 and IL-1β. This process is exacerbated by direct interactions with the intestinal epithelium, leading to recurrent damage and regenerative inflammation. Such an environment fosters the proliferation of genotoxic microorganisms in the gut, causing oxidative stress and, as a result, accumulating DNA damage within the intestinal epithelium, culminating in tumorigenesis (21,22). Key inflammatory mediators implicated in this process include TNF-α, IL-6, IL-11, IL-10 and TGF-β. IL-21 has been proven to facilitate the progression of inflammation-associated CRC in murine models of CRC (23). In experiments involving dextran sulfate-induced chronic colitis, an increase in expression of IL-21 was observed in the colon of affected mice; conversely, mice deficient in IL-21 exhibit mitigated colitis and a notable decrease in colonic tumor formation (24). Notably, the down-regulation of IL-21 is associated with increased levels of IFNγ and diminished IL-6 and IL-17 in colon tumors, underscoring the anti-tumor effects of IFNγ and the pro-tumor properties of IL-6 and IL-17 (25). IL-22, belonging to the IL-10 cytokine family, has key roles in warding off pathogens and repairing enterocytes (26,27). IL-22 facilitates CRC progression through the activation of STAT3 in tumor cells (28–30) and signals epithelial cells to produce nitric oxide, which contributes to the accumulation of genetic modifications (31).

Helicobacter species have also been linked to inflammatory processes in the gastrointestinal tract, leading to the upregulation of pro-inflammatory cytokines such as IL-1α, IL-1β, IFN-γ and TNF-α (32–34). In the Adenomatous Polyposis Coli minus (ApcMIN) murine model of spontaneous CRC, Wu et al (35) demonstrated that infestation by enterotoxigenic Bacteroides fragilis (ETBF) induces colitis and accelerates the cancerous process of tumors, primarily mediated by the induction of IL-17A.

The aforementioned immune mediators influence CRC development by directly or indirectly modulating signaling pathways within tumor cells. Key transcription factors are NF-κB and STAT3, both of which serve key roles in promoting cancer through inflammatory mechanisms (36–39). The NF-κB pathway is activated by cytokines such as TNF-α and IL-17, while STAT3 activation occurs in response to IL-6, IL-11 and IL-23, with studies confirming its tumor-promoting roles. NF-κB signaling is implicated in cancer progression through its activity in both neoplastic and tumor-infiltrating immune cells (40,41). In murine models, NF-κB activation in immune cells leads to the generation of pro-inflammatory cytokines such as TNF-α, IL-17 and IL-23, thereby facilitating cancer development (42,43). Additionally, genes involved in cell survival and proliferation, including Bcl-xL, Bcl-2, cellular inhibitor of apoptotic protein 2, myeloid cell leukemia 1 and survivin, are upregulated by STAT3, enhancing cancer cell proliferation and viability (44). Activated STAT3 promotes the progression of the cancer cell cycle by driving the expression of genes encoding c-Myc and cyclins B and D (45,46). In summary, the intra-tumoral inflammatory microenvironment promotes cancer development through the activation of NF-κB and STAT3 signaling pathways, leading to the upregulation of pro-survival and cell cycle-promoting genes.

Production of cancer-associated metabolites

Gut microbiota are instrumental in the production and degradation of intestinal contents, particularly in the metabolism of dietary components and pharmaceuticals. They regulate numerous products of metabolism, including secondary bile acids, H2S and reactive oxygen species (ROS) derived from high-fat diet, impacting the incidence and progression of CRC by regulating DNA damage, inflammatory levels, apoptosis and the activity of carcinogens (41).

H2S

H2S is primarily involved in colon cancer etiology via its capacity to induce DNA damage, release free radicals, promote colonic mucosal inflammation and stimulate hyperproliferation of colonic mucosa. H2S inhibits key metabolic functions such as cytochrome oxidase activity and butyrate use, as well as mucus synthesis and DNA methylation.

ROS

Prolonged exposure to oxidative damage induced by ROS is a notable factor contributing to DNA mutations, which is a key element in colon cancer development. ROS also facilitate colon cancer cell invasion and proliferation (47).

Secondary bile acids

Elevated concentrations of fecal bile acids are associated with increased colon cancer incidence in humans (48). In the intestine, unabsorbed bile acids in the enterohepatic circulation undergo conversion to secondary bile acids such as deoxycholic and lithocholic acid through microbial action, particularly by bile salt hydrolase-positive species such as Clostridium spp (49). Administering secondary bile acids to mice exacerbates inflammatory damage and tumor promotion, with underlying mechanisms involving the stimulation of ROS and reactive nitrogen species (RNS), DNA damage, mutation induction and apoptosis resistance (50).

Overall, the interplay of gut microbes, such as sulfidogenic bacteria (Fusobacterium, Desulfovibrio and Bilophila wadsworth), leads to the production of H2S, which shows notable genotoxic potential, causing DNA damage that results in genomic instability (51,52). In CRC cells, H2S inhibits mitochondrial functionality, elevates adenosine triphosphate turnover and enhances glycolytic activity (53–55). Furthermore, H2S exposure has been associated with the modulation of pro-angiogenic pathways, implicated in endothelial cell dynamics and promotion of tumorigenesis through pathways involving AKT and ERK1/2 (56–59).

The interplay between F. nucleatum and CRC further elucidates these mechanisms: FadA, a surface virulence factor of F. nucleatum, facilitates the binding to E-cadherin, inducing pro-inflammatory cytokine production while inhibiting the tumor-suppressive functions of E-cadherin. This promotes activation of β-catenin signaling pathways, resulting in inflammatory and pro-oncogenic cascades (60). Additionally, nitrogen-containing compounds, particularly N-nitroso compounds generated by nitroreductase activity, promote DNA alkylation and chromosomal mutations within intestinal cells (61,62). Polyamines originating from arginine metabolism by gut microbes exert toxic influences at high concentrations and are associated with various diseases, including cancer (63,64).

In conclusion, microbial activity within the gastrointestinal tract notably influences risk of CRC and progression through the disruption of mucosal homeostasis and the induction of DNA damage.

Release of genotoxins and virulence factors

Pathogenic bacteria promote carcinogenic effects through the production of virulence factors. These virulence factors primarily fall into two categories. The first category includes genotoxic agents, which directly induce DNA damage or chromosomal instability. These genotoxins may also compromise the DNA repair mechanisms, giving rise to the accumulation of mutations that result in cell proliferation disorders and tumor development. For example, certain strains of Escherichia coli possess genotoxins such as cytotoxic necrotizing factor, cycle-inhibiting factor and colibactin. Colibactin is a secondary metabolite that damages DNA, produced via its pks island. In addition, members of the Enterobacteriaceae family, including Citrobacter koseri, Klebsiella pneumoniae and Enterobacter aerogenes, produce colibactin (65,66). Colibactin-associated E. coli (CoPEC) can avoid autophagic degradation within infected epithelial cells, giving rise to DNA alkylation, which results in double-stranded DNA breaks. Colibactin interferes with the human cell cycle and contributes to genome lability. Furthermore, the internalization of CoPEC strains is associated with increased production of ROS, which further exacerbates the incidence of double-strand DNA breaks (67). Notably, CoPEC infection is associated with a decrease in tumor-infiltrating T lymphocytes, giving rise to increased resistance to immunization therapy in both human and mouse models (68,69).

The second category encompasses more aggressive virulence factors that stimulate epithelial cell proliferation and foster malignant transformations by modulating gene expression, thereby compromising the intestinal epithelial mucosal barrier. ETBF strain produces the B. fragilis toxin (BFT) (70). BFT has been implicated in disrupting the protective layer of the epidermis and promoting the cleavage of E-cadherin via γ-secretase-dependent mechanisms (71). This cleavage not only increases intestinal barrier permeability but also enhances signaling associated with E-cadherin and β-catenin in enterocytes (72). Additionally, BFT stimulates the transcription and translation of the proto-oncogene c-Myc in CRC cells, leading to enhanced cell multiplication (73).

BFT can activate intracellular signalling pathways, including STAT-3, NF-κB and p38 mitogen-activated protein kinase (74). Another mechanism fostering increased proliferation is the induction of B. fragilis-associated long non-coding RNA, which activates the RAS homolog in the mammalian target of rapamycin signaling pathway, thus promoting tumor growth in CRC (75). Furthermore, BFT inhibits apoptosis in epithelial cells by upregulating cellular inhibitors of apoptosis protein-2 (76).

In mouse models, purified BFT upregulates the enzyme spermine oxidase (SMO) in colonic epithelial cells. SMO, which is highly expressed in inflammatory conditions, results in elevated ROS production and DNA damage (77,78). In a colonic adenoma-carcinoma progression model involving somatic APC inactivation, BFT-induced disruption of the intestinal barrier leads to inflammatory responses mediated by IL-23 and IL-17. This inflammation results in DNA damage within epithelial cells, facilitating tumor formation (79). BFT promotes the release of pro-inflammatory signals that drive regulatory T cell/T helper cell 17 responses from the colonic epithelium, promoting inflammatory pathways and resulting in the transformation of enterocytes into cancerous entities.

Oxidative stress

Oxidative stress arises from a disequilibrium between ROS, RNS and antioxidant defenses (80). This adversely impacts cellular biomolecules, disrupts cytomembrane and induces DNA fission and damage (81). Oxidative stress activates the NF-κB pathway and upregulates the expression of pro-inflammatory cytokines and anti-apoptotic signals (82,83).

ROS production can occur due to the activity of intestinal microbiota and immune cells, such as macrophages and neutrophils, in response to inflammatory stimuli from pathogenic bacteria or other environmental cues (17,84). Certain bacteria, including Lactobacillus and Bifidobacterium, generate RNS, while Enterococcus faecalis promotes the progression of CRC by producing hydroxyl radicals that induce gene saltation and chromosome fissions (85).

The body uses various antioxidative mechanisms to restore balance during oxidative stress, including DNA repair pathways. Key DNA repair proteins, which include endo- and exonuclease, glycosylases, DNA ligases and DNA polymerases, are key for maintaining genomic stability (86). For example, DNA glycosylases have key roles in repairing and removing oxidized bases from DNA, predominantly through base excision repair (87). Additional oxidative damage is managed by nucleotide excision repair and mismatch repair (MMR) systems (88). Certain enteropathogenic E. coli strains inhibit the MMR system, as observed in colitis-induced CRC models (89,90). Furthermore, in APCmin/+ MMR-deficient mice, gut microbiota could induce CRC in epithelial cells deficient in MMR, underscoring the interactions between microbial communities and host genomic integrity (91).

In summary, pathogenic bacteria contribute to CRC through multifaceted mechanisms, including the release of genotoxins and aggressive virulence factors that impair cellular function and genomic integrity. By systematically studying the carcinogenic potential of gut microbiota and their distribution, specific microbial profiles associated with heightened cancer risk may be identified, leading to early clinical interventions for CRC. Moreover, non-invasive tests that detect oncogenic gut bacteria may serve as valuable tools for assessing CRC risk, fostering improvements in preventive screening strategies for emerging forms of intestinal malignancy.

Mechanism of probiotics in cancer prevention and therapy

Modification of the intestinal microbiota composition

Healthy gut microbiota typically exhibit a higher proportion of beneficial bacteria than pathogenic organisms. An imbalance between these can lead to chronic inflammation and dysbiosis, markedly increasing the risk of developing CRC (92,93).

Regular probiotic consumption positively influences both the quantity and diversity of gut microbial populations (94–97). Notably, strains such as Lactobacillus acidophilus, Bifidobacterium bifidum and B. infantum effectively modulate the gut microbiota by decreasing the prevalence of pathogenic bacteria, including Escherichia, Pseudomonas, Helicobacter and Chlamydia, while promoting beneficial probiotic populations such as Lactobacillus. This shift in microbiota composition is associated with a decreased risk of colon cancer, manifesting as decreased tumor incidence, multiplicity and growth (98).

Probiotic microorganisms decrease harmful bacterial populations through several mechanisms, including competition for nutrients, growth factors and adherence sites. Certain probiotics produce antibacterial compounds, such as bacteriocins, reuterin, hydrogen peroxide and lactic acid, which inhibit or eliminate the growth of pathogenic organisms in the gut (99). Thus, the favorable alteration of the intestinal microbiota composition is associated with a lower risk of developing CRC.

Thus, probiotics enhance the intestinal microbiota composition by increasing the abundance of commensal and protective bacteria, while decreasing the prevalence of pathogenic strains. This modulation serves a key role in the prevention and management of CRC.

Changes in metabolic activity of the intestinal microbiota

Modifying microbial metabolism via the intake of probiotics can affect the risk of CRC by changing the activity of enzymes. Certain enzymes, involving β-glucosidase, β-glucuronidase, nitrate reductase, azoreductase and 7-α-dehydroxylase, convert polycyclic aromatic hydrocarbons, heterocyclic aromatic amines and primary bile acids into active carcinogens (100). In vitro (101–104), in vivo (105–108) and clinical investigations (109) have proved that the intake of selected probiotic strains decreases activity of these harmful enzymes, most notably β-glucuronidase and nitrate reductase. By decreasing the populations of pathogenic bacteria within the gut microbiota, probiotics decrease production of intestinal carcinogenic compounds (110). For example, certain strains of Lactobacillus inhibit the enzymatic activity associated with the dehydroxylation of primary bile acids, and L. rhamnosus GG can decrease β-glucuronidase activity (111). Additionally, oral intake of L. acidophilus and B. bifidum for >3 weeks decreases nitroreductase activity in stool samples (112).

Consequently, probiotics serve a key role in regulating enzyme activity associated with carcinogenic pathways, thus preventing the generation of carcinogens and facilitating both the prevention and therapy of CRC.

Improvement of the intestinal barrier

Probiotics serve a considerable role in CRC prevention by modifying the properties of the intestinal barrier, which includes factors such as colonic pH, mucin (MUC) production and the expression of cellular junction proteins. These modifications restore the integrity of the intestinal barrier and prevent excessive enterocyte proliferation and adhesion (113,114).

Metabolism of probiotics leads to the production of organic acids such as lactic, acetic and propionic acid. These organic acids serve to lower intestinal pH (115). An acidic environment in the colon inhibits the proliferation of putrefactive and pathogenic microorganisms, as well as the activity of bacterial enzymes responsible for generating carcinogenic compounds (116). For example, Bifidobacterium species produce notable amounts of organic acids through glucose fermentation, effectively lowering intestinal pH and suppressing the proliferation of pathogenic bacteria and fungi, including Shigella, Typhi, Proteus and Pseudomonas aeruginosa (117). Furthermore, a low pH environment prevents the adhesion of these pathogens and their toxins to enterocytes (118,119). In vitro studies have corroborated that Lactobacillus bulgaricus inhibits the proliferation of clinical isolates of H. pylori, while Lactobacillus casei subsp. rhamnosus Lcr35 decreases proliferation of enteropathogenic and enterotoxigenic E. coli and K. pneumonia (120–122). The inhibition effect is predominantly noted under acidic pH conditions, implying that probiotics modulate pH levels to enhance their survival and maintain metabolic activity in a relatively low pH environment.

Furthermore, probiotics stimulate the expression of specific adhesive proteins, including MUCs. MUCs are classified as either secretory or transmembrane glycoproteins, with the gel-forming secretory MUCs (MUC-2, MUC-5AC, MUC-5B and MUC-6) forming the primary components of the mucosal layer. These MUCs are synthesized by specialized mucus-secreting cells, known as goblet cells, which are distributed throughout the gastrointestinal epithelium (123). MUC genes, including MUC1, MUC2, MUC3, MUC4 and MUC5AC, are expressed in the human colon (124), and abnormal MUC expression is associated with numerous types of gastrointestinal disease, such as inflammatory bowel disease and CRC, which are characterized by dysregulated intestinal barrier (125). Probiotic intervention can enhance the gastrointestinal mucosal barrier, impeding pathogenic bacteria adhesion (126). For example, the administration of L. plantarum and L. rhamnosus notably increases the expression of MUC-2 and MUC-3 in enterocytes, thereby fortifying the mucosal barrier and decreasing sensitivity to pathogen invasion (127). The effects of these Lactobacilli species have been validated in an HT-29 cell culture model, where they inhibited the adhesion of enteropathogenic E. coli and subsequent infection of the intestinal epithelium (128).

Inflammation and carcinogenesis increase intestinal permeability, primarily by altering the components and expression of cellular junction proteins that facilitate adhesion between colonocytes. These proteins, located at the apical junction between cells, form tight junctions through membrane-spanning proteins that are associated with the cytoskeleton of colonocytes (129).

Lipoteichoic acids (LTA) produced by probiotics regulates extracorporeal epithelial barrier function (130). Treatment with LTA from Lactobacilli increases the expression of tight junction protein 1 (ZO-1) through a toll-like receptor (TLR)-2 dependent pathway (131). Furthermore, pretreatment with LTA from Bacillus subtilis improves barrier integrity and increases tight junction protein levels, including ZO-1 and claudin-3 (132). Additionally, peptidoglycan secreted by Lactobacillus and Bifidobacterium species elevates the levels of tight junction proteins, such as claudins, occludin and ZO-1, thus improving both permeability and integrity of the intestinal barrier via TLR2 signaling (133). Notably, Lactobacillus and Bifidobacterium also enhance the production of secretory IgA and increase levels of ZO-1 and occludin in the Caco-2 cell line (134).

In conclusion, leveraging the barrier-repairing functions of probiotics offers prospective tactics for the prevention of CRC by maintaining the integrity of the intestinal barrier and attenuating the risks associated with pathogenic invasion.

Immunomodulation

Immunomodulation has a key part in preventing the immune evasion of CRC cells (135). Probiotics influence the proliferation and differentiation of T cells, particularly by enhancing the ratio of effector to regulatory T cells (136).

Beyond their general immunomodulatory effects, probiotics activate the immune system by increasing the production of immunoglobulins, enhancing the activity of macrophages and lymphocytes and boosting the production of IFN-γ (137). For example, probiotic supplementation stimulates macrophages while simultaneously inhibiting the proliferation of CRC cells (138). Similarly, therapy with the L. casei strain Shirota increases T cell-mediated cytotoxic activity against CRC cells (139) and activates natural killer (NK) cells, which are key in preventing tumorigenesis in C57Bl/6 mouse models (140,141). Enhancement of NK cell activity is associated with the production of IL-12, a cytokine integral to NK cell function (142). Additionally, the combination of resistant starch and B. lactis markedly increases the apoptosis rate of rat CRC cells (143). In a clinical trial, administration of B. polyfermenticus in patients with CRC resulted in improved counts of circulating CD4+ and CD8+ T cells as well as elevated levels of IgG (144).

Furthermore, probiotics downregulate the expression of enzymes involved in the production of pro-inflammatory prostaglandins, thereby decreasing cellular proliferation and the inflammatory response. Purified exopolysaccharides from L. acidophilus exhibit modulatory effects on apoptosis and NF-κB signaling pathways in human CRC (145). Moreover, L. reuteri inhibits NF-κB signaling, which leads to decreased expression of cyclooxygenase-2 (COX-2), cyclin D1 and Bcl-2, while inducing the expression of pro-apoptotic factor Bax (146). COX-2 is a key enzyme in the synthesis of prostaglandin E2, a compound known to promote inflammatory responses (147). Therefore, downregulating COX-2 expression exerts substantial effects on inflammatory activity (148).

The integration of immunotherapy and radiotherapy that uses gut microbiota immunomodulation has shown promising initial results in treating CRC (149). However, further research into the role of intestinal microbiota in CRC is key for developing personalized interventions that enhance anticancer efficacy while minimizing adverse effects.

Binding and degradation of carcinogenic compounds in the intestinal lumen

The presence of toxic compounds in the intestinal lumen creates a conducive environment for cancer cell proliferation. By contrast, probiotics can interact with these carcinogenic compounds through mechanisms such as cation exchange, effectively binding to them and facilitating their excretion from the body. This binding process decreases risk of cancer cell proliferation (150).

Several strains of probiotics disintegrate and inactivate cancer-causing substances, particularly N-nitroso compounds and heterocyclic aromatic amines. Strains such as B. longum, L. acidophilus and Streptococcus salivarius can bind to and promote the excretion of heterocyclic aromatic amines and mutagenics, including 2-amino-3,4-dimethylimidazo (4,5-f) quinoline (MeIQ) and 2-amino-3-methyl-3H-imidazo (4,5-f) quinoline in feces (151). Zhang and Ohta (152) investigated the binding capacity of heterocyclic amines {Trp-P1 (3-amino-1,4-dimethyl-[5H]pyridine[4,3-b]indole)}, Glu-P-1 (pyrolyzates of glutamic acid), Phe-P-1 (isolated from a phenylalanine pyrolyzate), MeIQ [2-amino-3,4-dimethylimidazo(4,5-f)quinoline], IQ [2-amino-3,4-dimethylimidazo (4,5-f)quinoline] and MeIQX [2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline] with both whole cells and cell wall skeleton components of L. acidophilus IFO (Institute for Fermentation, Osaka) 13951 and B. bifidum IFO 14252, indicating that the intact peptidoglycan of cell walls contributes to the xenobiotic-binding activity of these bacteria (153). Similarly, studies have reported the binding capacity of heterocyclic amines by various human intestinal and lactic acid bacteria (154,155). The capacity for binding and degrading carcinogenic compounds depends on the specific bacterial strain, microbial viability, type of carcinogenic compound, probiotic dosage and environmental factors such as pH, bile salt presence and gastrointestinal enzymes (156,157).

Probiotics may exert detoxifying abilities against mycotoxins, which are carcinogenic substances (158,159). Mycotoxins, produced by fungi, contaminate food products made for human consumption or animal feed. Certain dairy probiotics, such as Propionibacteria, effectively remove mycotoxins from aqueous solutions in vitro (160,161). Additionally, dairy Propionibacteria bind to cyanotoxins such as microcystin-leucine-arginine, as well as heavy metals such as lead and cadmium (162,163).

Thus, future studies should investigate the ability of probiotics to degrade and detoxify carcinogenic compounds to provide novel insights into CRC prevention.

Inhibition of proliferation and induction of apoptosis in cancer cells

Apoptosis, or programmed cell death, is a mechanism in regulating cellular equilibrium and eliminating cancer cells. This process involves three interrelated pathways: The perforin/granzyme, mitochondrial/intrinsic and death receptor/extrinsic pathways (164–166). Key genes involved in apoptotic regulation include TNF, inhibitors of apoptosis proteins, caspases, Bcl-2 and p53 (167).

For example, Chen et al (168) revealed that the apoptosis in SW620 tumor cells induced by probiotics is associated with increased expression of Caspase-3 and decreased expression of Bcl-2. The Bcl-2 family comprises both antiapoptotic, such as Bcl-2, and proapoptotic proteins, such as Bax. The balance between these proteins is key for regulating the intrinsic apoptotic pathway. An elevated Bax/Bcl-2 ratio is associated with heightened levels of activated caspase-3, resulting in the increased sensibility of cancer cells to fade out. Probiotics have significant apoptosis-inducing effects on cancer cells, but they do not affect normal colonic epithelial cells. If probiotics have apoptosis-inducing effects on normal cells, they may disrupt the integrity of the intestinal barrier and thus impair intestinal defenses, thus creating favourable conditions for the development and progression of CRC. Therefore, when using probiotics for therapeutic purposes, their potential effects on normal cells need to be carefully assessed to ensure the safety and efficacy of the treatment.

Probiotics abduct fadeout in cancer cells through mechanisms involving the modulation of Bax/Bcl-2 ratio and caspase activation (169–171) (Fig. 2). Konishi et al (172) investigated a probiotic-derived tumor suppressor molecule known as iron-chromium, which inhibits colon cancer progression via JNK-mediated pathways. An in vitro study revealed that strains such as E. faecium RM11 and L. fermentum RM28, both present in acidophilus milk, decrease the diffusion of Caco-2 colon cancer cells by 21 and 23%, respectively (173). Furthermore, L. acidophilus and B. bifidum display enhanced cytotoxic effects against colon cancer cell lines by upregulating Bax, IFN-γ and TNF-α expression, while downregulating Bcl-2 expression (174).

Figure 2.

Inhibition of proliferation and induction of apoptosis in cancer cells. (A) Probiotics increase the expression of caspase-3 and inhibit the expression of Bcl-2, leading to a resurgence of reduced susceptibility of CRC cells. (B) Lactobacillus acidophilus induces apoptosis in CRC cells by increasing the mRNA expression of survivin while decreasing the expression of SMAC. (C) Lactobacillus plantarum increases the expression of MAPK and blocks PTEN signaling, inhibiting the proliferation of CRC cells. (D) Propionibacterium activates mitochondria and increases the production of short-chain fatty acids, thereby inducing apoptosis in CRC cells. (E) Escherichia coli induces apoptosis in CRC cells by forming micropores in the plasma membrane and leads to cell cycle arrest in G1 phase. (F) Lactobacillus acidophilus and Bifidobacterium bifidum increase Bax, IFN-γ and TNF-α expression while inhibiting Bcl-2 expression, resulting in increased sensitivity of CRC cells to cytotoxic effects. (G) Nissen produced by probiotics inhibits the proliferation of cancer cells by increasing intracellular calcium levels, inducing cell cycle arrest and activating the expression of Chac1. (H) Probiotic-derived molecule known as iron-chromium blocks the JNK-mediated pathway to inhibit colon cancer progression. CRC, colorectal cancer; SMAC, second mitochondria-derived activator of caspase; Chac1, intracellular calcium levels, abducting cell cycle arrest and stimulating the cation transport regulator homolog 1; HNSCC, head and neck squamous cell carcinoma.

Alshuail et al (175) reported that apoptosis can occur through mitochondrial pore formation pathways, which facilitate caspase activation. Moreover, Propionibacterium induces apoptosis in CRC cells via short-chain fatty acids that act on mitochondria (176). Moreover, L. acidophilus has been shown to induce apoptosis by increasing the mRNA expression of survivin while decreasing the expression of second mitochondria-derived activator of caspases (177). L. casei considerably increases expression of the human β-defensin 2 gene in the HT-29 colon cancer cell line (178). Małaczewska and Kaczorek-Łukowska (179) further demonstrated that nisin, a bacteriocin, abducts fadeout and decreases multiplication in head and neck squamous cell carcinoma cells by increasing intracellular calcium levels, abducting cell cycle arrest and stimulating the cation transport regulator homolog 1.

Overall, there is an ongoing effort in research to clarify the fadeout of potential of probiotics against cancer (180,181). As research on probiotics continues, the ability of probiotics to induce apoptosis is gradually being uncovered, presenting the opportunity to use probiotic-based regimens as adjuvant therapy alongside conventional anticancer chemotherapy (182,183). Despite the identification of numerous apoptotic proteins, the precise molecular mechanisms by which they exert their effects remain to be fully elucidated.

Production of biological substances with anticarcinogenic activity [SCFAs and conjugated linoleic acid (CLA)]

SCFAs and CLA are bioactive compounds generated by intestinal probiotics, which exhibit notable anticarcinogenic properties (184,185). SCFAs are effective in promoting apoptosis in cancer cells and inhibiting the formation of high levels of secondary bile acids, thereby serving as a preventive measure against CRC (186). CLA exerts its anticancer effects through unique anti-proliferative and pro-apoptotic mechanisms (187).

Role of SCFAs

SCFAs have a notable impact in maintaining intestinal barrier integrity. They enhance the secretion of IL-18, MUC2 and antibacterial peptides, while also increasing the expression of tightly linked proteins in intestinal epithelial cells (188,189). SCFAs are conducive to the improvement of the lining of gut function by regulating pH levels within the gut (190).

SCFAs influence immune responses by modulating T cell function through G-protein-coupled receptors (GPRs), such as GPR41, GPR43 and GPR109A, as well as Olfactory receptor 78 receptor signaling. They also inhibit histone deacetylase (HDAC), which impacts the inhibition of NF-κB (191,192). Notably, butyrate inhibits HDAC activity, leading to histone hyperacetylation, which results in changes to the expression of genes involved in cell cycle regulation, differentiation, apoptosis and cancer progression (193–195). For example, hyperacetylation can activate the p21 gene, contributing to G1 cell cycle arrest (196).

SCFAs promote the migration of neutrophils to the site of cellulitis and enhance their phagocytic ability. They inhibit the secretion of pro-inflammatory cytokines such as IL-6, IL-8, IL-1β and TNF-α by intestinal macrophages and may promote intestinal IgA production by B cells (197,198). SCFAs have been revealed to regulate the production of regulatory T and T helper cell subsets in response to different cytokine environments (199,200).

SCFAs accelerate programmed cell death and restrain the proliferation of tumor cells, effectively hindering tumor development. For example, butyrate regulates Bcl-2 family proteins and induces apoptosis by upregulating BAK and downregulating Bcl-xL (201,202). It also decreases the levels of cyclin D1 and c-myc, which are key for intestinal tumor development, via transcriptional suppression in human colorectal adenocarcinoma cells (203,204). Moreover, both propionate and butyrate are associated with the modulation of autophagy and type II programmed cell death in CRC cells (205,206).

Role of CLA

CLA, an important metabolin synthesized by probiotics such as Lactobacillus and Bifidobacterium, has been recognized for its anticancer effects (207). The antiproliferative and apoptosis-promoting activity associated with CLA arises from its capacity to activate peroxisome proliferator-activated receptor γ (PPARγ), which has a key role in adjusting lipid elimination, apoptosis and immunological system functions (208). Various species of probiotic, such as Lactobacilli and Bifidobacteria, transform LA into CLA, with strains such as L. bulgaricus and Streptococcus thermophilus demonstrating higher conversion efficiency (209).

Studies have indicated that CLA decreases cell proliferation and induces apoptosis in cancer cells by downregulating key pathways. For instance, CLA diminishes ErbB3 gene expression and inhibits the PI3K/Akt pathway, in addition to upregulating caspases 3 and 9 while decreasing Bcl-2 expression (210–212). In the context of HT-29 human CRC cells, CLA induces apoptosis by suppressing insulin-like growth factor (IGF)-II synthesis and downregulating IGF-I receptor signaling (213). Furthermore, CLA promotes G1 cell cycle arrest in CRC cells and inhibits the production of eicosanoids through two mechanisms: Replacing arachidonic acid in the cytomembrane and interfering with the activity of epoxidase and fatty acid oxidase, enzymes primarily in charge of eicosanoid synthesis (214,215). CLA produced by probiotics upregulates the PPARγ gene, which participates in biological processes, including the control of apoptosis. As a result, CLA induces apoptosis and decreases viability in cancer cells (216,217).

Previous research has highlighted a strain derived from the human intestine, B. breve CCFM683, which demonstrates notable isomerase activity for free LA and is effective in ameliorating inflammatory bowel disease in mouse models through the accumulation of CLA and modulation of gut microbiota (218,219). Similar effects have been reported in other bifidobacterial strains, such as B. bifidum S17 and B. longum subsp.

In conclusion, SCFAs and CLA generated by probiotics serve essential roles in cancer prevention through mechanisms including apoptosis induction, modulation of inflammation and enhancement of intestinal barrier functions. To capitalize on the potential of probiotics in the prevention and therapy of CRC, further study is warranted to identify mechanisms of action on human colon cancer cells.

Effects on other mutagenic and carcinogenic factors

Probiotics may affect mutagenic and carcinogenic agents, thereby serving a role in cancer prevention. They can modify the activity of enzymes involved in expelling toxin processes from cells, preventing the accumulation of toxins within the cells and thereby mitigating the effects of free radicals and potential carcinogens. Furthermore, probiotics exert their antitumor effects through mechanisms such as competitive adhesion mechanisms, increasing the diversity of the intestinal flora, and inhibiting the activity of harmful enzymes in the gut (220,221).

Imbalances in intestinal microbiota give rise to an increased release of harmful enzymes such as β-glucuronidase, β-glucosidase, azoreductase and nitroreductase, resulting in the generation of carcinogenic substances (222). These enzymes can generate toxic metabolites, including H2S, aromatic amines, carcinogenic aglycones and acetaldehyde (223). For example, the bacterium Clostridium perfringens produces IQ from dietary components by secreting β-glucuronidase (224). Similarly, azoreductase enzymes, commonly synthesized by bacteria such as Staphylococcus, Salmonella, Clostridium and Enterococcus, metabolize mixtures such as dyes and pharmaceuticals, leading to the generation of toxic aromatic amines (225,226). The intake of probiotics decreases activity of these harmful enzymes through multiple mechanisms. Lactobacillus strains inhibit the enzymes responsible for the primary bile acid dehydroxylation, while L. rhamnosus GG specifically reduces β-glucuronidase activity (227). Additionally, oral supplementation of L. acidophilus and B. bifidum for 3 weeks decreases nitroreductase activity in stool samples (228).

Lactic acid bacteria bind to and degrade carcinogenic compounds such as nitrosamines and heterocyclic amines, as well as produce antioxidant enzymes such as superoxide dismutase (SOD), glutathione S-transferase (GST) and glutathione reductase. These enzymes absorb reactive intermediates, thus decreasing the activity of several carcinogenic compounds, including 1,2-dimethylhydrazine (DMH) and N-methyl-N'-nitro-N-nitrosoguanidine (113,229). A study revealed that administering DMH to rats results in decreased activities of glutathione peroxidase (GPx), GST, SOD, catalase (CAT) and glutathione (230). Conversely, co-administration of probiotics such as L. plantarum and rhamnosus GG with chemotherapy notably elevates the activities of these enzymes, suggesting that probiotics alleviate oxidative stress during colon cancer treatment (231).

Furthermore, studies indicate that probiotics not only reduce free radicals but also upregulate antioxidant-associated genes and stimulate the production of antioxidative enzymes to increase overall antioxidative activities (232–234). The presence of selenium may support the selective enhancement of antioxidative activities by certain probiotics (235). L. brevis LSe, when cultured in selenium-enriched conditions, demonstrated greater radical scavenging capability compared with culture in selenium-free media (236).

Exopolysaccharides (EPSs) extracted from probiotic sources, such as E. faecium, L. plantarum RJF4 and Weissella cibaria GA44, exert promising antioxidative effects by scavenging free radicals. The efficacy of these EPS primarily hinges upon their saccharide constitution, formula weight and branched chain structures. Additionally, fermented products from probiotics, such as peptide extracts, exhibit notable antioxidant potential (237–239). For example, glycine-rich antimicrobial peptide YD1, derived from B. amyloliquefaciens has been reported to increase the mRNA and protein levels of antioxidant enzymes such as SOD1, CAT and GPx-1 while decreasing nitric oxide and ROS levels (240).

In summary, probiotics inhibit development of CRC through multiple pathways, presenting potential avenues for clinical exploration of the treatment of CRC.

Gut microbiota in CRC treatment

Traditional approaches for managing CRC primarily involve chemotherapy and radiotherapy. However, these treatments often disrupt intestinal microbiota, potentially exacerbating the condition of the patient. Studies indicate that probiotics complement modern therapy by enhancing efficacy and minimizing toxic side effects (241–243).

Chemotherapy

Chemotherapy is the standard treatment for CRC. However, this therapeutic approach often leads to disruptions in the intestinal microbiota, which exacerbates adverse effects and diminishes therapeutic efficacy. One potential strategy to counteract these negative effects is restoration of the gut microbiota (244).

The gut microbiota has a notable influence on the pharmacological actions of chemotherapeutics, including cyclophosphamide, irinotecan, oxaliplatin and gemcitabine (245). The administration of these chemotherapy drugs results in an imbalance of gut microbiota, such as decreased levels of Lactobacilli, Bacteroides and butyric acid-producing bacteria. Concurrently, there is often an increase in pathogenic bacteria, including F. nucleatum, E. coli and sulfate-reducing bacteria (246). This ecological imbalance leads to decreased chemotherapy efficacy, heightened toxicity, emergence of drug resistance and potentially the progression of CRC (247). For example, studies have revealed an increase in the number of pathogen types, such as Enterobacteriaceae, Fusobacteria and Proteobacteria, following irinotecan treatment in tumor-bearing rats (248–250).

Gut microbiota mitigate the adverse side effects associated with chemotherapy in patients with CRC. For example, polysaccharides derived from Calothrix hongkongensis modulate the intestinal microbiota by increasing the populations of propionic and butyric acid-producing microorganisms and decreasing the abundance of Lactobacillus, Prevotella_UCG-001 and Rikenellaceae_RC9_gut_group. This modulation positively affects the TLR signaling pathway, which leads to improved outcomes concerning 5-fluorouracil (5-FU)-induced intestinal mucositis and malnutrition (251). Furthermore, probiotic transplantation considerably alleviates symptoms such as weight loss and diarrhea in a CRC mouse model treated with irinotecan, while also decreasing intestinal mucosal damage (249). Additionally, a study involving 150 patients with CRC undergoing treatment with 5-FU revealed that intervention with L. rhamnosus GG during chemotherapy markedly decreased patient mortality, improved gastrointestinal symptoms such as diarrhea and decreased the necessary chemotherapy dosage (252).

Gut microbial metabolites can also improve the anti-tumor effect of drugs in colorectal cancer treatment. Previous studies indicate that butyric acid, a metabolite produced by gut microbiota, enhances the anti-tumor cytotoxicity of CD8+ T cells both in vitro and in vivo by promoting the IL-12 signaling pathway in an inhibitor of DNA binding 2-dependent manner. Butyric acid has also been associated with increased the anti-tumor efficacy of oxaliplatin (253,254).

Further research on intestinal microbiota may offer novel insight and strategies for improving chemotherapy modalities in CRC.

Radiation therapy

Numerous studies have highlighted alterations in intestinal microbiota in patients undergoing radiation therapy, with dysbiosis linked to the emergence of complications associated with radiation treatment (255,256). Analysis of the intestinal microbiota following radiotherapy has identified a decrease in beneficial commensal bacteria such as Bifidobacterium, E. faecalis and certain Clostridium species, accompanied by an increase in Lactobacillus spp. and Enterococcus spp (257). These changes indicate severe side effects, dysbiosis of the intestinal microbiota and disruption to the overall microbial composition (258).

Specific gut microorganisms, such as Bifidobacteria, Lactobacillus acidophilus, Streptococcus and L. casei, alleviate the severity of radiation enteritis and associated diarrhea (259). Although there are fewer studies directly addressing the influence of gut microbiota on the efficacy of radiation therapy in patients with CRC, previous findings suggest that oral microbiota impact both the effectiveness and prognosis of radiation treatment for CRC. Notably, F. nucleatum can migrate to and colonize the intestinal tract, where it heavily populates the intestinal mucosa of patients with CRC, thereby negatively affecting the efficacy and outcomes of radiotherapy. Treatment with metronidazole has been shown to counteract this adverse effect (260–262).

Fecal microbiota transplantation (FMT) is a potential therapeutic strategy for improving gastrointestinal function and maintaining enterocytes following tumor radiotherapy. This approach decreases radiation-induced gastrointestinal toxicity and enhances the prognosis of patients undergoing radiation treatment for tumors (263).

In summary, both chemotherapy and radiation therapy notably affect gut microbiota, potentially impacting treatment outcomes. As understanding of these interactions increases, integrating probiotics and FMT into cancer care regimens may offer valuable avenues for enhancing the efficacy and tolerability of standard cancer treatments.

Immune checkpoint inhibitors (ICIs)

Immunotherapy has emerged as a promising treatment for various types of cancer, including CRC (264). The US Food and Drug Administration has approved the use of immunotherapy as a second-line treatment specifically for tumors that are deficient in MMR or exhibit high microsatellite instability (265). ICIs are key components of immunotherapy that activate T cells, enabling them to mount an effective antitumor response (266).

ICIs, which are typically monoclonal antibodies, work by blocking the interaction between programmed cell death protein 1 (PD-1) and its ligand PD-L1 or by targeting cytotoxic T lymphocyte antigen 4. This blockade facilitates the activation of cytotoxic T lymphocytes, enhancing their ability to attack tumor cells (267).

Recent research has indicated that specific intestinal microbiota enhance the therapeutic effects of ICIs. For example, isolated strains such as L. testosterone, B. pseudopodium and Bacteroides europaeus from mice potentiate the effects of immune checkpoint blockade in CRC models. Notably, inosine, a metabolite produced by B. pseudopodium, promotes the activation of antitumor T cells when co-stimulatory signals are present (268–270). This indicates microbial metabolite-immunity pathways may enhance immunotherapy, providing valuable insight for the development of microbe-assisted therapy (271).

Specifically, oral administration of B. bifidum influences the immune response in CRC by maturing dendritic cells, enhancing their function, increasing cytokine secretion and activating tumor-specific T cells (272). The intestinal microbiota is implicated in ICI-induced colitis: Administration of probiotics, including strains from Bacteroides and Burkholderia, as well as FMT, alleviate ICI-induced colitis (273).

FMT

FMT is an emerging biological therapy that involves transferring stool from healthy donors to patients with altered microbiota suspected of contributing to disease (274). This approach aims to restore a healthy, diverse microbiome in the gastrointestinal tract, thereby promoting eubiosis and ameliorating gastrointestinal disorders (275). FMT is an established treatment for recurrent and refractory Clostridioides difficile infection, demonstrating success rates of 80 to 90% (276,277).

In animal studies involving CRC, FMT markedly increases the abundance of beneficial gut bacteria, such as Muribaculaceae, Lachnospiraceae, Prevotellaceae, Ruminococcaceae and Erysipelotrichaceae, effectively alleviating intestinal dysbiosis (278–280). Additionally, FMT is associated with the augmentation of immune cells, including CD4+ and CD8+ T and CD49b NK cells, and it increases expression levels of cytokines such as IFN-γ and IL-10 while decreasing levels of IL-17 and STAT3. These changes create a microenvironment that hinders the progression of CRC (281).

FMT is effective in reversing microbial dysbiosis associated with CRC (282). Restoring gut microbiota balance inhibits progression of CRC by suppressing intestinal inflammation and enhancing anti-cancer immune responses mediated by immune cells and inflammatory factors (283). This highlights the importance of understanding the interactions between intestinal microbiota and CRC, especially when considering FMT as a potential therapeutic intervention in clinical practice.

Conclusion

Intestinal microbiota serve a key role in the pathogenesis and modulation of CRC. Although pathogenic bacteria and their oncogenic mechanisms require further investigation, identifying the risk factors associated with CRC by detecting specific intestinal bacteria offers novel avenues for preventive strategies. Analyzing the distribution and composition of the gut microbiota provides insight into microbial profiles that indicate an increased cancer risk, aiding in early intervention and treatment efforts for CRC.

Furthermore, a growing body of evidence supporting the role of probiotics in CRC prevention and therapy underscores their potential for clinical applications. The negative effect of traditional treatments on the gut microbiota highlights the need for strategies that leverage probiotics to enhance efficacy while minimizing toxic side effects. However, resistance to chemotherapy drugs is a key factor affecting traditional therapy and the mechanisms of reversal of resistance to chemotherapy drugs in the gut microbiota are rarely reported. Future studies should further explore the mechanisms of different intestinal microbes regulating drug resistance in CRC, providing a new window for the treatment of CRC. The association between the intestinal microbiota and CRC holds promise for personalized approaches to the diagnosis, prevention and management of CRC.

Acknowledgements

Not applicable.

Funding

The present study was supported by Provincial Undergraduate College Basal Research Foundation of Heilongjiang Province (grant no. 2019-KYYWF-1342).

Availability of data and materials

Not applicable.

Authors' contributions

WS, SM and DM wrote and edited the manuscript. SM conceived the study. CW and JZ edited the manuscript. All authors have read and approved the final manuscript. Data authentication is not applicable.

Ethics approval and consent to participate

Not applicable.

Patient consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Glossary

Abbreviations

Abbreviations:

CRC

colorectal cancer

ETBF

enterotoxigenic Bacteroides fragilis

ROS

reactive oxygen species

RNS

reactive nitrogen species

CoPEC

colibactin-associated E. coli

BFT

B. fragilis toxin

SMO

spermine oxidase

MMR

mismatch repair

MUC

mucin

LTA

lipoteichoic acid

NK

natural killer

COX-2

cyclooxygenase-2

MeIQ

2-amino-3,4-dimethylimidazo (4,5-f)quinoline

CLA

conjugated linoleic acid

GPR

G-protein-coupled receptor

HDAC

histone deacetylase

PPARγ

peroxisome proliferator-activated receptor γ

IGF

insulin-like growth factor

EcN

E.coli Nissle 1917

SOD

superoxide dismutase

GST

glutathione S-transferase

DMH

1,2-dimethylhydrazine

GPx

glutathione peroxidase

CAT

catalase

EPS

exopolysaccharide

FMT

fecal microbiota transplantation

ICI

immune checkpoint inhibitor

PD-1

cell death protein 1

APC

adenomatosis polyposis coli

ZO-1

tight junction protein 1

TLR

Toll-like receptor

References

1 

Zhang C, Stampfl-Mattersberger M, Ruckser R and Sebesta C: Colorectal cancer. Wien Med Wochenschr. 173:216–220. 2023.(In German). View Article : Google Scholar : PubMed/NCBI

2 

Yu CY, Han JX, Zhang J, Jiang P, Shen C, Guo F, Tang J, Yan T, Tian X, Zhu X, et al: A 16q22.1 variant confers susceptibility to colorectal cancer as a distal regulator of ZFP90. Oncogene. 39:1347–1360. 2020. View Article : Google Scholar : PubMed/NCBI

3 

Chaplin A, Rodriguez RM, Segura-Sampedro JJ, Ochogavía-Seguí A, Romaguera D and Barceló-Coblijn G: Insights behind the relationship between colorectal cancer and obesity: Is visceral adipose tissue the missing link. Int J Mol Sci. 23:131282022. View Article : Google Scholar : PubMed/NCBI

4 

Sawicki T, Ruszkowska M, Danielewicz A, Niedźwiedzka E, Arłukowicz T and Przybyłowicz KE: A review of colorectal cancer in terms of epidemiology, risk factors, development, symptoms and diagnosis. Cancers (Basel). 13:20252021. View Article : Google Scholar : PubMed/NCBI

5 

Wang F, Sun N, Zeng H, Gao Y, Zhang N and Zhang W: Selenium deficiency leads to inflammation, autophagy, endoplasmic reticulum stress, apoptosis and contraction abnormalities via affecting intestinal flora in intestinal smooth muscle of mice. Front Immunol. 13:9476552022. View Article : Google Scholar : PubMed/NCBI

6 

Tang Y, Zhang X, Wang Y, Guo Y, Zhu P, Li G, Zhang J, Ma Q and Zhao L: Dietary ellagic acid ameliorated Clostridium perfringens-induced subclinical necrotic enteritis in broilers via regulating inflammation and cecal microbiota. J Anim Sci Biotechnol. 13:472022. View Article : Google Scholar : PubMed/NCBI

7 

Masheghati F, Asgharzadeh MR, Jafari A, Masoudi N and Maleki-Kakelar H: The role of gut microbiota and probiotics in preventing, treating, and boosting the immune system in colorectal cancer. Life Sci. 344:1225292024. View Article : Google Scholar : PubMed/NCBI

8 

Lu Y, Luo X, Yang D, Li Y, Gong T, Li B, Cheng J, Chen R, Guo X and Yuan W: Effects of probiotic supplementation on related side effects after chemoradiotherapy in cancer patients. Front Oncol. 12:10321452022. View Article : Google Scholar : PubMed/NCBI

9 

Lehouritis P, Stanton M, McCarthy FO, Jeavons M and Tangney M: Activation of multiple chemotherapeutic prodrugs by the natural enzymolome of tumour-localised probiotic bacteria. J Control Release. 222:9–17. 2016. View Article : Google Scholar : PubMed/NCBI

10 

Xiong H, Wang J, Chang Z, Hu H, Yuan Z, Zhu Y, Hu Z, Wang C, Liu Y, Wang Y, et al: Gut microbiota display alternative profiles in patients with early-onset colorectal cancer. Front Cell Infect Microbiol. 12:10369462022. View Article : Google Scholar : PubMed/NCBI

11 

Sánchez-Alcoholado L, Laborda-Illanes A, Otero A, Ordóñez R, González-González A, Plaza-Andrades I, Ramos-Molina B, Gómez-Millán J and Queipo-Ortuño MI: Relationships of gut microbiota composition, short-chain fatty acids and polyamines with the pathological response to neoadjuvant radiochemotherapy in colorectal cancer patients. Int J Mol Sci. 22:95492021. View Article : Google Scholar : PubMed/NCBI

12 

Bi D, Zhu Y, Gao Y, Li H, Zhu X, Wei R, Xie R, Cai C, Wei Q and Qin H: Profiling fusobacterium infection at high taxonomic resolution reveals lineage-specific correlations in colorectal cancer. Nat Commun. 13:33362022. View Article : Google Scholar : PubMed/NCBI

13 

Castro-Mejía JL, O'Ferrall S, Krych Ł, O'Mahony E, Namusoke H, Lanyero B, Kot W, Nabukeera-Barungi N, Michaelsen KF, Mølgaard C, et al: Restitution of gut microbiota in Ugandan children administered with probiotics (Lactobacillus rhamnosus GG and Bifidobacterium animalis subsp. lactis BB-12) during treatment for severe acute malnutrition. Gut Microbes. 11:855–867. 2020. View Article : Google Scholar : PubMed/NCBI

14 

Park YE and Kim JH: Revolutionizing gut health: exploring the role of gut microbiota and the potential of microbiome-based therapies in lower gastrointestinal diseases. Kosin Med J. 38:98–106. 2023. View Article : Google Scholar

15 

Sobhani I, Tap J, Roudot-Thoraval F, Roperch JP, Letulle S, Langella P, Corthier G, Tran Van Nhieu J and Furet JP: Microbial dysbiosis in colorectal cancer (CRC) patients. PLoS One. 6:e163932011. View Article : Google Scholar : PubMed/NCBI

16 

Fong W, Li Q and Yu J: Gut microbiota modulation: A novel strategy for prevention and treatment of colorectal cancer. Oncogene. 39:4925–4943. 2020. View Article : Google Scholar : PubMed/NCBI

17 

Cheng Y, Ling Z and Li L: The intestinal microbiota and colorectal cancer. Front Immunol. 11:6150562020. View Article : Google Scholar : PubMed/NCBI

18 

Grigoryan H, Schiffman C, Gunter MJ, Naccarati A, Polidoro S, Dagnino S, Dudoit S, Vineis P and Rappaport SM: Cys34 adductomics links colorectal cancer with the gut microbiota and redox biology. Cancer Res. 79:6024–6031. 2019. View Article : Google Scholar : PubMed/NCBI

19 

Ying HQ, Chen W, Xiong CF, Wang Y, Li XJ and Cheng XX: Quantification of fibrinogen-to-pre-albumin ratio provides an integrating parameter for differential diagnosis and risk stratification of early-stage colorectal cancer. Cancer Cell Int. 22:1372022. View Article : Google Scholar : PubMed/NCBI

20 

Song C, Duan F, Ju T, Qin Y, Zeng D, Shan S, Shi Y, Zhang Y and Lu W: Eleutheroside E supplementation prevents radiation-induced cognitive impairment and activates PKA signaling via gut microbiota. Commun Biol. 5:6802022. View Article : Google Scholar : PubMed/NCBI

21 

Li R, Huang X, Yang L, Liang X, Huang W, Lai KP and Zhou L: Integrated analysis reveals the targets and mechanisms in immunosuppressive effect of mesalazine on ulcerative colitis. Front Nutr. 9:8676922022. View Article : Google Scholar : PubMed/NCBI

22 

Fan H, Hao X, Gao Y, Yang J, Liu A, Su Y and Xia Y: Nodosin exerts an anti-colorectal cancer effect by inhibiting proliferation and triggering complex cell death in vitro and in vivo. Front Pharmacol. 13:9432722022. View Article : Google Scholar : PubMed/NCBI

23 

Wan F, Zhong R, Wang M, Zhou Y, Chen Y, Yi B, Hou F, Liu L, Zhao Y, Chen L and Zhang H: Caffeic acid supplement alleviates colonic inflammation and oxidative stress potentially through improved gut microbiota community in mice. Front Microbiol. 12:7842112021. View Article : Google Scholar : PubMed/NCBI

24 

Krieg C, Weber LM, Fosso B, Marzano M, Hardiman G, Olcina MM, Domingo E, El Aidy S, Mallah K, Robinson MD and Guglietta S: Complement downregulation promotes an inflammatory signature that renders colorectal cancer susceptible to immunotherapy. J Immunother Cancer. 10:e0047172022. View Article : Google Scholar : PubMed/NCBI

25 

Leonard WJ and Spolski R: Interleukin-21: A modulator of lymphoid proliferation, apoptosis and differentiation. Nat Rev Immunol. 5:688–698. 2005. View Article : Google Scholar : PubMed/NCBI

26 

Takahashi J, Yamamoto M, Yasukawa H, Nohara S, Nagata T, Shimozono K, Yanai T, Sasaki T, Okabe K, Shibata T, et al: Interleukin-22 directly activates myocardial STAT3 (Signal Transducer and Activator of Transcription-3) signaling pathway and prevents myocardial ischemia reperfusion injury. J Am Heart Assoc. 9:e0148142020. View Article : Google Scholar : PubMed/NCBI

27 

Xiao Z, Liu L, Pei X, Sun W, Jin Y, Yang ST and Wang M: A potential probiotic for diarrhea: Clostridium tyrobutyricum protects against LPS-induced epithelial dysfunction via IL-22 Produced By Th17 cells in the ileum. Front Immunol. 12:7582272021. View Article : Google Scholar : PubMed/NCBI

28 

Zhao Q, Cheng X, Guo J, Bi Y, Kuang L, Ren J, Zhong J, Pan L, Zhang X, Guo Y, et al: MLKL inhibits intestinal tumorigenesis by suppressing STAT3 signaling pathway. Int J Biol Sci. 17:869–881. 2021. View Article : Google Scholar : PubMed/NCBI

29 

Xiaoyu P, Chao G, Lihua D and Pengyu C: Gut bacteria affect the tumoral immune milieu: Distorting the efficacy of immunotherapy or not? Gut Microbes. 11:691–705. 2020. View Article : Google Scholar : PubMed/NCBI

30 

Karstens KF, Kempski J, Giannou AD, Pelczar P, Steglich B, Steurer S, Freiwald E, Woestemeier A, Konczalla L, Tachezy M, et al: Anti-inflammatory microenvironment of esophageal adenocarcinomas negatively impacts survival. Cancer Immunol Immunother. 6:1043–1056. 2020. View Article : Google Scholar : PubMed/NCBI

31 

Liou CJ, Chen YL, Yu MC, Yeh KW, Shen SC and Huang WC: Sesamol alleviates airway hyperresponsiveness and oxidative stress in asthmatic mice. Antioxidants (Basel). 9:2952020. View Article : Google Scholar : PubMed/NCBI

32 

Wang H, Huang J, Ding Y, Zhou J, Gao G, Han H, Zhou J, Ke L, Rao P, Chen T and Zhang L: Nanoparticles isolated from porcine bone soup ameliorated dextran sulfate sodium-induced colitis and regulated gut microbiota in mice. Front Nutr. 9:8214042022. View Article : Google Scholar : PubMed/NCBI

33 

Wang K, Guo J, Chang X and Gui S: Painong-san extract alleviates dextran sulfate sodium-induced colitis in mice by modulating gut microbiota, restoring intestinal barrier function and attenuating TLR4/NF-κB signaling cascades. J Pharm Biomed Anal. 209:1145292022. View Article : Google Scholar : PubMed/NCBI

34 

Bai J, Zhao J, Al-Ansi W, Wang J, Xue L, Liu J, Wang Y, Fan M, Qian H, Li Y and Wang L: Oat β-glucan alleviates DSS-induced colitis via regulating gut microbiota metabolism in mice. Food Funct. 12:8976–8993. 2021. View Article : Google Scholar : PubMed/NCBI

35 

Wu S, Rhee KJ, Albesiano E, Rabizadeh S, Wu X, Yen HR, Huso DL, Brancati FL, Wick E, McAllister F, et al: A human colonic commensal promotes colon tumorigenesis via activation of T helper type 17 T cell responses. Nat Med. 15:1016–1022. 2009. View Article : Google Scholar : PubMed/NCBI

36 

Tian L, Long F, Hao Y, Li B, Li Y, Tang Y, Li J, Zhao Q, Chen J and Liu M: A cancer associated fibroblasts-related six-gene panel for anti-PD-1 therapy in melanoma driven by weighted correlation network analysis and supervised machine learning. Front Med (Lausanne). 9:8803262022. View Article : Google Scholar : PubMed/NCBI

37 

Nyiramana MM, Cho SB, Kim EJ, Kim MJ, Ryu JH, Nam HJ, Kim NG, Park SH, Choi YJ, Kang SS, et al: Sea hare hydrolysate-induced reduction of human non-small cell lung cancer cell growth through regulation of macrophage polarization and non-apoptotic regulated cell death pathways. Cancers (Basel). 12:7262020. View Article : Google Scholar : PubMed/NCBI

38 

Dmitrieva-Posocco O, Dzutsev A, Posocco DF, Hou V, Yuan W, Thovarai V, Mufazalov IA, Gunzer M, Shilovskiy IP, Khaitov MR, et al: Cell-type-specific responses to interleukin-1 control microbial invasion and tumor-elicited inflammation in colorectal cancer. Immunity. 50:166–180.e7. 2019. View Article : Google Scholar : PubMed/NCBI

39 

Hahn YI, Saeidi S, Kim SJ, Park SY, Song NY, Zheng J, Kim DH, Lee HB, Han W, Noh DY, et al: STAT3 stabilizes IKKα protein through direct interaction in transformed and cancerous human breast epithelial cells. Cancers (Basel). 13:822020. View Article : Google Scholar : PubMed/NCBI

40 

Franz A, Coscia F, Shen C, Charaoui L, Mann M and Sander C: Molecular response to PARP1 inhibition in ovarian cancer cells as determined by mass spectrometry based proteomics. J Ovarian Res. 14:1402021. View Article : Google Scholar : PubMed/NCBI

41 

Pan Z, He Y, Zhu W, Xu T, Hu X and Huang P: A dynamic transcription factor signature along the colorectal adenoma-carcinoma sequence in patients with co-occurrent adenoma and carcinoma. Front Oncol. 11:5974472021. View Article : Google Scholar : PubMed/NCBI

42 

Icard P, Fournel L, Wu Z, Alifano M and Lincet H: Interconnection between metabolism and cell cycle in cancer. Trends Biochem Sci. 44:490–501. 2019. View Article : Google Scholar : PubMed/NCBI

43 

Tian X, Wei W, Cao Y, Ao T, Huang F, Javed R, Wang X, Fan J, Zhang Y, Liu Y, et al: Gingival mesenchymal stem cell-derived exosomes are immunosuppressive in preventing collagen-induced arthritis. J Cell Mol Med. 26:693–708. 2022. View Article : Google Scholar : PubMed/NCBI

44 

Kim BR, Ha J, Kang E and Cho S: Regulation of signal transducer and activator of transcription 3 activation by dual-specificity phosphatase3. BMB Rep. 53:335–340. 2020. View Article : Google Scholar : PubMed/NCBI

45 

Zhang M, Dai Z, Zhao X, Wang G and Lai R: Anticarin β inhibits human glioma progression by suppressing cancer stemness via STAT3. Front Oncol. 11:7156732021. View Article : Google Scholar : PubMed/NCBI

46 

Shen J, Zhang M, Zhang K, Qin Y, Liu M, Liang S, Chen D and and Peng M: Effect of Angelica polysaccharide on mouse myeloid-derived suppressor cells. Front Immunol. 13:9892302022. View Article : Google Scholar : PubMed/NCBI

47 

Al-Warhi T, Al-Karmalawy AA, Elmaaty AA, Alshubramy MA, Abdel-Motaal M, Majrashi TA, Asem M, Nabil A, Eldehna WM and Sharaky M: Biological evaluation, docking studies, and in silico ADME prediction of some pyrimidine and pyridine derivatives as potential EGFR WT and EGFR T790M inhibitors. J Enzyme Inhib Med Chem. 38:176–191. 2023. View Article : Google Scholar : PubMed/NCBI

48 

Yu J, Li S, Guo J, Xu Z, Zheng J and Sun X: Farnesoid X receptor antagonizes Wnt/β-catenin signaling in colorectal tumorigenesis. Cell Death Dis. 11:6402020. View Article : Google Scholar : PubMed/NCBI

49 

McPherson J, Hu C, Begum K, Wang W, Lancaster C, Gonzales-Luna AJ, Loveall C, Silverman MH, Alam MJ and Garey KW: Functional and metagenomic evaluation of ibezapolstat for early evaluation of anti-recurrence effects in clostridioides difficile infection. Antimicrob Agents Chemother. 66:e02244212022. View Article : Google Scholar : PubMed/NCBI

50 

Bernstein H, Bernstein C, Payne CM and Dvorak K: Bile acids as endogenous etiologic agents in gastrointestinal cancer. World J Gastroenterol. 15:3329–3340. 2009. View Article : Google Scholar : PubMed/NCBI

51 

Wang X, Ye P, Fang L, Ge S, Huang F, Polverini PJ, Heng W, Zheng L, Hu Q, Yan F and Wang W: Active smoking induces aberrations in digestive tract microbiota of rats. Front Cell Infect Microbiol. 11:7372042021. View Article : Google Scholar : PubMed/NCBI

52 

Maarsingh JD, Łaniewski P and Herbst-Kralovetz MM: Immunometabolic and potential tumor-promoting changes in 3D cervical cell models infected with bacterial vaginosis-associated bacteria. Commun Biol. 5:7252022. View Article : Google Scholar : PubMed/NCBI

53 

Sánchez-Quintero MJ, Rodríguez-Díaz C, Rodríguez-González FJ, Fernández-Castañer A, García-Fuentes E and López-Gómez C: Role of mitochondria in inflammatory bowel diseases: A systematic review. Int J Mol Sci. 24:171242023. View Article : Google Scholar : PubMed/NCBI

54 

Huang D, Jing G and Zhu S: Regulation of mitochondrial respiration by hydrogen sulfide. Antioxidants (Basel). 12:16442023. View Article : Google Scholar : PubMed/NCBI

55 

Blachier F, Andriamihaja M, Larraufie P, Ahn E, Lan A and Kim E: Production of hydrogen sulfide by the intestinal microbiota and epithelial cells and consequences for the colonic and rectal mucosa. Am J Physiol Gastrointest Liver Physiol. 320:G125–G135. 2021. View Article : Google Scholar : PubMed/NCBI

56 

Roudsari LC and West JL: Studying the influence of angiogenesis in in vitro cancer model systems. Adv Drug Deliv Rev. 97:250–259. 2016. View Article : Google Scholar : PubMed/NCBI

57 

Wang Z, Lan R, Xu Y, Zuo J, Han X, Phouthapane V, Luo Z and Miao J: Taurine alleviates streptococcus uberis-induced inflammation by activating autophagy in mammary epithelial cells. Front Immunol. 12:6311132021. View Article : Google Scholar : PubMed/NCBI

58 

Karpiński TM, Ożarowski M and Stasiewicz M: Carcinogenic microbiota and its role in colorectal cancer development. Semin Cancer Biol. 86:420–430. 2022. View Article : Google Scholar : PubMed/NCBI

59 

Zhang S, Bian H, Li X, Wu H, Bi Q, Yan Y and Wang Y: Hydrogen sulfide promotes cell proliferation of oral cancer through activation of the COX2/AKT/ERK1/2 axis. Oncol Rep. 35:2825–2832. 2016. View Article : Google Scholar : PubMed/NCBI

60 

Kelly D, Yang L and Pei Z: Gut microbiota, fusobacteria, and colorectal cancer. Diseases. 6:1092018. View Article : Google Scholar : PubMed/NCBI

61 

Kiziltan T, Baran A, Kankaynar M, Şenol O, Sulukan E, Yildirim S and Ceyhun SB: Effects of the food colorant carmoisine on zebrafish embryos at a wide range of concentrations. Arch Toxicol. 96:1089–1099. 2022. View Article : Google Scholar : PubMed/NCBI

62 

Bulanda S and Janoszka B: Consumption of thermally processed meat containing carcinogenic compounds (Polycyclic Aromatic Hydrocarbons and Heterocyclic Aromatic Amines) versus a risk of some cancers in humans and the possibility of reducing their formation by natural food additives-a literature review. Int J Environ Res Public Health. 19:47812022. View Article : Google Scholar : PubMed/NCBI

63 

Liu R, Lin X, Li Z, Li Q and Bi K: Quantitative metabolomics for investigating the value of polyamines in the early diagnosis and therapy of colorectal cancer. Oncotarget. 9:4583–4592. 2017. View Article : Google Scholar : PubMed/NCBI

64 

Meng X, Peng J, Xie X, Yu F, Wang W, Pan Q, Jin H, Huang X, Yu H, Li S, et al: Roles of lncRNA LVBU in regulating urea cycle/polyamine synthesis axis to promote colorectal carcinoma progression. Oncogene. 41:4231–4243. 2022. View Article : Google Scholar : PubMed/NCBI

65 

Auvray F, Perrat A, Arimizu Y, Chagneau CV, Bossuet-Greif N, Massip C, Brugère H, Nougayrède JP, Hayashi T, Branchu P, et al: Insights into the acquisition of the pks island and production of colibactin in the Escherichia coli population. Microb Genom. 7:0005792021.PubMed/NCBI

66 

Chagneau CV, Payros D, Tang-Fichaux M, Auvray F, Nougayrède JP and Oswald E: The pks island: A bacterial swiss army knife? Colibactin: Beyond DNA damage and cancer. Trends Microbiol. 30:1146–1159. 2022. View Article : Google Scholar : PubMed/NCBI

67 

Wami H, Wallenstein A, Sauer D, Stoll M, von Bünau R, Oswald E, Müller R and Dobrindt U: Insights into evolution and coexistence of the colibactin-and yersiniabactin secondary metabolite determinants in enterobacterial populations. Microb Genom. 7:0005772021.PubMed/NCBI

68 

Lopès A, Billard E, Casse AH, Villéger R, Veziant J, Roche G, Carrier G, Sauvanet P, Briat A, Pagès F, et al: Colibactin-positive Escherichia coli induce a procarcinogenic immune environment leading to immunotherapy resistance in colorectal cancer. Int J Cancer. 146:3147–3159. 2020. View Article : Google Scholar : PubMed/NCBI

69 

Salesse L, Lucas C, Hoang MHT, Sauvanet P, Rezard A, Rosenstiel P, Damon-Soubeyrand C, Barnich N, Godfraind C, Dalmasso G and Nguyen HTT: Colibactin-producing escherichia coli induce the formation of invasive carcinomas in a chronic inflammation-associated mouse model. Cancers (Basel). 13:20602021. View Article : Google Scholar : PubMed/NCBI

70 

Dahmus JD, Kotler DL, Kastenberg DM and Kistler CA: The gut microbiome and colorectal cancer: A review of bacterial pathogenesis. J Gastrointest Oncol. 9:769–777. 2018. View Article : Google Scholar : PubMed/NCBI

71 

Oh H, Kim J, Park J, Choi Z, Hong J, Jeon BY, Ka H and Hong M: Structure-based molecular characterization of a putative aspartic proteinase from Bacteroides fragilis. Biochem Biophys Res Commun. 738:1505472024. View Article : Google Scholar : PubMed/NCBI

72 

Lee CG, Hwang S, Gwon SY, Park C, Jo M, Hong JE and Rhee KJ: Bacteroides fragilis toxin induces intestinal epithelial cell secretion of interleukin-8 by the E-Cadherin/β-Catenin/NF-κB dependent pathway. Biomedicines. 10:8272022. View Article : Google Scholar : PubMed/NCBI

73 

Valguarnera E and Wardenburg JB: Good gone bad: One toxin away from disease for bacteroides fragilis. J Mol Biol. 432:765–785. 2020. View Article : Google Scholar : PubMed/NCBI

74 

Ko SH, Jeon JI, Woo HA and Kim JM: Bacteroides fragilis enterotoxin upregulates heme oxygenase-1 in dendritic cells via reactive oxygen species-, mitogen-activated protein kinase-, and Nrf2-dependent pathway. World J Gastroenterol. 26:291–306. 2020. View Article : Google Scholar : PubMed/NCBI

75 

Bao Y, Tang J, Qian Y, Sun T, Chen H, Chen Z, Sun D, Zhong M, Chen H, Hong J, et al: Long noncoding RNA BFAL1 mediates enterotoxigenic Bacteroides fragilis-related carcinogenesis in colorectal cancer via the RHEB/mTOR pathway. Cell Death Dis. 10:6752019. View Article : Google Scholar : PubMed/NCBI

76 

Goodwin AC, Destefano Shields CE, Wu S, Huso DL, Wu X, Murray-Stewart TR, Hacker-Prietz A, Rabizadeh S, Woster PM, Sears CL and Casero RA Jr: Polyamine catabolism contributes to enterotoxigenic Bacteroides fragilis-induced colon tumorigenesis. Proc Natl Acad Sci USA. 108:15354–15359. 2011. View Article : Google Scholar : PubMed/NCBI

77 

Thiele Orberg E, Fan H, Tam AJ, Dejea CM, Destefano Shields CE, Wu S, Chung L, Finard BB, Wu X, Fathi P, et al: The myeloid immune signature of enterotoxigenic Bacteroides fragilis-induced murine colon tumorigenesis. Mucosal Immunol. 10:421–433. 2017. View Article : Google Scholar : PubMed/NCBI

78 

Knippel RJ, Drewes JL and Sears CL: The cancer microbiome: recent highlights and knowledge gaps. Cancer Discov. 11:2378–2395. 2021. View Article : Google Scholar : PubMed/NCBI

79 

Grivennikov SI, Wang K, Mucida D, Stewart CA, Schnabl B, Jauch D, Taniguchi K, Yu GY, Osterreicher CH, Hung KE, et al: Adenoma-linked barrier defects and microbial products drive IL-23/IL-17-mediated tumour growth. Nature. 491:254–258. 2012. View Article : Google Scholar : PubMed/NCBI

80 

Zhang J, Wu S, Wang Q, Yuan Q, Li Y, Reboredo-Rodríguez P, Varela-López A, He Z, Wu F, Hu H and Liu X: Oxidative stress amelioration of novel peptides extracted from enzymatic hydrolysates of Chinese pecan cake. Int J Mol Sci. 23:120862022. View Article : Google Scholar : PubMed/NCBI

81 

Zhang L, Yang L, Luo Y, Dong L and Chen F: Acrylamide-induced hepatotoxicity through oxidative stress: mechanisms and interventions. Antioxid Redox Signal. 38:1122–1137. 2023. View Article : Google Scholar : PubMed/NCBI

82 

Kong Y, Li M, Liang G, Linhai Y, Li S, Zhuang Y, Ruomin L, Xiumei C and Guiqin W: Effects of dietary curcumin inhibit deltamethrin-induced oxidative stress, inflammation and cell apoptosis in Channa argus via Nrf2 and NF-κB signaling pathways. Aquaculture. 540:7367442021. View Article : Google Scholar

83 

Luan C, Lu Z, Chen J, Chen M, Zhao R and Li X: Thalidomide alleviates apoptosis, oxidative damage and inflammation induced by pemphigus vulgaris IgG in HaCat cells and neonatal mice through MyD88. Drug Des Devel Ther. 17:2821–2839. 2023. View Article : Google Scholar : PubMed/NCBI

84 

Wu J, Li Q and Fu X: Fusobacterium nucleatum contributes to the carcinogenesis of colorectal cancer by inducing inflammation and suppressing host immunity. Transl Oncol. 12:846–851. 2019. View Article : Google Scholar : PubMed/NCBI

85 

Dariya B, Aliya S, Merchant N, Alam A and Nagaraju GP: Colorectal cancer biology, diagnosis, and therapeutic approaches. Crit Rev Oncog. 25:71–94. 2020. View Article : Google Scholar : PubMed/NCBI

86 

Wang Y, Su M, Chen Y, Huang X, Ruan L, Lv Q and Li L: Research progress on the role and mechanism of DNA damage repair in germ cell development. Front Endocrinol (Lausanne). 14:12342802023. View Article : Google Scholar : PubMed/NCBI

87 

Huang Z, Chen Y and Zhang Y: Mitochondrial reactive oxygen species cause major oxidative mitochondrial DNA damages and repair pathways. J Biosci. 45:842020. View Article : Google Scholar : PubMed/NCBI

88 

Lad SB, Upadhyay M, Thorat P, Nair D, Moseley GW, Srivastava S, Pradeepkumar PI and Kondabagil K: Biochemical reconstitution of the mimiviral base excision repair pathway. J Mol Biol. 435:1681882023. View Article : Google Scholar : PubMed/NCBI

89 

Triner D, Devenport SN, Ramakrishnan SK, Ma X, Frieler RA, Greenson JK, Inohara N, Nunez G, Colacino JA, Mortensen RM and Shah YM: Neutrophils restrict tumor-associated microbiota to reduce growth and invasion of colon tumors in mice. Gastroenterology. 156:1467–1482. 2019. View Article : Google Scholar : PubMed/NCBI

90 

Huang JR, Wang ST, Wei MN, Liu K, Fu JW, Xing ZH and Shi Z: Piperlongumine alleviates mouse colitis and colitis-associated colorectal cancer. Front Pharmacol. 11:5868852020. View Article : Google Scholar : PubMed/NCBI

91 

Wang CZ, Zhang CF, Luo Y, Yao H, Yu C, Chen L, Yuan J, Huang WH, Wan JY, Zeng J, et al: Baicalein, an enteric microbial metabolite, suppresses gut inflammation and cancer progression in ApcMin/+ mice. Clin Transl Oncol. 22:1013–1022. 2020. View Article : Google Scholar : PubMed/NCBI

92 

Ahlawat S, Kumar P, Mohan H, Goyal S and Sharma KK: Inflammatory bowel disease: Tri-directional relationship between microbiota, immune system and intestinal epithelium. Crit Rev Microbiol. 47:254–273. 2021. View Article : Google Scholar : PubMed/NCBI

93 

Brasiel PGA, Dutra Luquetti SCP, Peluzio MDCG, Novaes RD and Gonçalves RV: Preclinical evidence of probiotics in colorectal carcinogenesis: A systematic review. Dig Dis Sci. 65:3197–3210. 2020. View Article : Google Scholar : PubMed/NCBI

94 

Hor YY, Lew LC, Jaafar MH, Lau AS, Ong JS, Kato T, Nakanishi Y, Azzam G, Azlan A, Ohno H and Liong MT: Lactobacillus sp. improved microbiota and metabolite profiles of aging rats. Pharmacol Res. 146:1043122019. View Article : Google Scholar : PubMed/NCBI

95 

Dong Y, Zhu J, Zhang M, Ge S and Zhao L: Probiotic Lactobacillus salivarius Ren prevent dimethylhydrazine-induced colorectal cancer through protein kinase B inhibition. Appl Microbiol Biotechnol. 104:7377–7389. 2020. View Article : Google Scholar : PubMed/NCBI

96 

Reis SK, Socca EAR, de Souza BR, Genaro SC, Durán N and Fávaro WJ: Effects of probiotic supplementation on chronic inflammatory process modulation in colorectal carcinogenesis. Tissue Cell. 87:1022932024. View Article : Google Scholar : PubMed/NCBI

97 

Casas-Solís J, Huizar-López MDR, Irecta-Nájera CA, Pita-López ML and Santerre A: immunomodulatory effect of lactobacillus casei in a murine model of colon carcinogenesis. Probiotics Antimicrob Proteins. 12:1012–1024. 2020. View Article : Google Scholar : PubMed/NCBI

98 

Agah S, Alizadeh AM, Mosav M, Ranji P, Khavari-Daneshvar H, Ghasemian F, Bahmani S and Tavassoli A: More protection of lactobacillus acidophilus than bifidobacterium bifidum probiotics on azoxymethane-induced mouse colon cancer. Probiotics Antimicrob Proteins. 11:857–864. 2019. View Article : Google Scholar : PubMed/NCBI

99 

Samanta S: Potential impacts of prebiotics and probiotics on cancer prevention. Anticancer Agents Med Chem. 22:605–628. 2022. View Article : Google Scholar : PubMed/NCBI

100 

Abu-Ghazaleh N, Chua WJ and Gopalan V: Intestinal microbiota and its association with colon cancer and red/processed meat consumption. J Gastroenterol Hepatol. 36:75–88. 2021. View Article : Google Scholar : PubMed/NCBI

101 

Śliżewska K, Markowiak-Kopeć P and Śliżewska W: The role of probiotics in cancer prevention. Cancers (Basel). 13:202020. View Article : Google Scholar : PubMed/NCBI

102 

Yixia Y, Sripetchwandee J, Chattipakorn N and Chattipakorn SC: The alterations of microbiota and pathological conditions in the gut of patients with colorectal cancer undergoing chemotherapy. Anaerobe. 68:1023612021. View Article : Google Scholar : PubMed/NCBI

103 

Freedman JC, Li J, Mi E and McClane BA: Identification of an important orphan histidine kinase for the initiation of sporulation and enterotoxin production by clostridium perfringens type F strain SM101. mBio. 10:e02674–18. 2019. View Article : Google Scholar : PubMed/NCBI

104 

Ma Y, Qu R, Zhang Y, Jiang C, Zhang Z and Fu W: Progress in the study of colorectal cancer caused by altered gut microbiota after cholecystectomy. Front Endocrinol (Lausanne). 13:8159992022. View Article : Google Scholar : PubMed/NCBI

105 

Nowak A, Śliżewska K, Błasiak J and Libudzisz Z: The influence of Lactobacillus casei DN 114 001 on the activity of faecal enzymes and genotoxicity of faecal water in the presence of heterocyclic aromatic amines. Anaerobe. 30:129–136. 2014. View Article : Google Scholar : PubMed/NCBI

106 

Verma A and Shukla G: Probiotics lactobacillus rhamnosus GG, lactobacillus acidophilus suppresses DMH-induced procarcinogenic fecal enzymes and preneoplastic aberrant crypt foci in early colon carcinogenesis in sprague dawley rats. Nutr Cancer. 65:84–91. 2013. View Article : Google Scholar : PubMed/NCBI

107 

Zhu J, Zhu C, Ge S, Zhang M, Jiang L, Cui J and Ren F: L actobacillus salivarius Ren prevent the early colorectal carcinogenesis in 1, 2-dimethylhydrazine-induced rat model. J Appl Microbiol. 117:208–216. 2014. View Article : Google Scholar : PubMed/NCBI

108 

Mohania D, Kansal VK, Sagwal R, Batish VK, Grover S and Shah D: Anticarcinogenic effect of probiotic dahi and piroxicam on DMH-induced colorectal carcinogenesis in wistar rats. American J Cancer Ther Pharm. 1:8–24. 2013.

109 

Samara J, Moossavi S, Alshaikh B, Ortega VA, Pettersen VK, Ferdous T, Hoops SL, Soraisham A, Vayalumkal J, Dersch-Mills D, et al: Supplementation with a probiotic mixture accelerates gut microbiome maturation and reduces intestinal inflammation in extremely preterm infants. Cell Host Microbe. 30:696–711.e5. 2022. View Article : Google Scholar : PubMed/NCBI

110 

Drago L: Probiotics and colon cancer. Microorganisms. 7:662019. View Article : Google Scholar : PubMed/NCBI

111 

Eslami M, Yousefi B, Kokhaei P, Hemati M, Nejad ZR, Arabkari V and Namdar A: Importance of probiotics in the prevention and treatment of colorectal cancer. J Cell Physiol. 234:17127–17143. 2019. View Article : Google Scholar : PubMed/NCBI

112 

Derebasi BN, Davran Bulut S, Aksoy Erden B, Sadeghian N, Taslimi P and Celebioglu HU: Effects of p-coumaric acid on probiotic properties of Lactobacillus acidophilus LA-5 and lacticaseibacillus rhamnosus GG. Arch Microbiol. 206:2232024. View Article : Google Scholar : PubMed/NCBI

113 

Dos Reis SA, da Conceição LL, Siqueira NP, Rosa DD, da Silva LL and Peluzio MD: Review of the mechanisms of probiotic actions in the prevention of colorectal cancer. Nutr Res. 37:1–19. 2017. View Article : Google Scholar : PubMed/NCBI

114 

Ho Do M, Seo YS and Park HY: Polysaccharides: Bowel health and gut microbiota. Crit Rev Food Sci Nutr. 61:1212–1224. 2021. View Article : Google Scholar : PubMed/NCBI

115 

Roberfroid M: Dietary fiber, inulin, and oligofructose: A review comparing their physiological effects. Crit Rev Food Sci Nutr. 33:103–148. 1993. View Article : Google Scholar : PubMed/NCBI

116 

Yeung CY, Chiang Chiau JS, Cheng ML, Chan WT, Chang SW, Chang YH, Jiang CB and Lee HC: Modulations of probiotics on gut microbiota in a 5-fluorouracil-induced mouse model of mucositis. J Gastroenterol Hepatol. 35:806–814. 2020. View Article : Google Scholar : PubMed/NCBI

117 

Gavzy SJ, Kensiski A, Lee ZL, Mongodin EF, Ma B and Bromberg JS: Bifidobacterium mechanisms of immune modulation and tolerance. Gut Microbes. 15:22911642023. View Article : Google Scholar : PubMed/NCBI

118 

Gyles CL: Shiga toxin-producing Escherichia coli: An overview. J Anim Sci. 85:E45–E62. 2007. View Article : Google Scholar : PubMed/NCBI

119 

Pearce SC, Weber GJ, van Sambeek DM, Soares JW, Racicot K and Breault DT: Intestinal enteroids recapitulate the effects of short-chain fatty acids on the intestinal epithelium. PLoS One. 15:e02302312020. View Article : Google Scholar : PubMed/NCBI

120 

Ji J and Yang H: Using probiotics as supplementation for Helicobacter pylori antibiotic therapy. Int J Mol Sci. 21:11362020. View Article : Google Scholar : PubMed/NCBI

121 

Fayol-Messaoudi D, Berger CN, Coconnier-Polter MH, Liévin-Le Moal V and Servin AL: pH-, Lactic acid-, and non-lactic acid-dependent activities of probiotic lactobacilli against salmonella enterica serovar typhimurium. Appl Environ Microbiol. 71:6008–6013. 2005. View Article : Google Scholar : PubMed/NCBI

122 

Li Y, Yang S, Lun J, Gao J, Gao X, Gong Z, Wan Y, He X and Cao H: Inhibitory effects of the lactobacillus rhamnosus GG effector Protein HM0539 on inflammatory response through the TLR4/MyD88/NF-ĸB axis. Front Immunol. 11:5514492020. View Article : Google Scholar : PubMed/NCBI

123 

Paone P and Cani PD: Mucus barrier, mucins and gut microbiota: The expected slimy partners? Gut. 69:2232–2243. 2020. View Article : Google Scholar : PubMed/NCBI

124 

Olli KE, Rapp C, O'Connell L, Collins CB, McNamee EN, Jensen O, Jedlicka P, Allison KC, Goldberg MS, Gerich ME, et al: Muc5ac expression protects the colonic barrier in experimental colitis. Inflamm Bowel Dis. 26:1353–1367. 2020. View Article : Google Scholar : PubMed/NCBI

125 

Kufe DW: MUC1-C in chronic inflammation and carcinogenesis; emergence as a target for cancer treatment. Carcinogenesis. 41:1173–1183. 2020. View Article : Google Scholar : PubMed/NCBI

126 

Martens EC, Neumann M and Desai MS: Interactions of commensal and pathogenic microorganisms with the intestinal mucosal barrier. Nat Rev Microbiol. 16:457–470. 2018. View Article : Google Scholar : PubMed/NCBI

127 

Etienne-Mesmin L, Chassaing B, Desvaux M, De Paepe K, Gresse R, Sauvaitre T, Forano E, de Wiele TV, Schüller S, Juge N and Blanquet-Diot S: Experimental models to study intestinal microbes-mucus interactions in health and disease. FEMS Microbiol Rev. 43:457–489. 2019. View Article : Google Scholar : PubMed/NCBI

128 

Fang J, Wang H, Zhou Y, Zhang H, Zhou H and Zhang X: Slimy partners: The mucus barrier and gut microbiome in ulcerative colitis. Exp Mol Med. 53:772–787. 2021. View Article : Google Scholar : PubMed/NCBI

129 

Ohland CL and MacNaughton WK: Probiotic bacteria and intestinal epithelial barrier function. Am J Physiol Gastrointest Liver Physiol. 298:G807–G819. 2010. View Article : Google Scholar : PubMed/NCBI

130 

Ren C, Zhang Q, de Haan BJ, Faas MM, Zhang H and de Vos P: Protective effects of lactic acid bacteria on gut epithelial barrier dysfunction are toll like receptor 2 and protein kinase C dependent. Food Funct. 11:1230–1234. 2020. View Article : Google Scholar : PubMed/NCBI

131 

Wan Z, Wang L, Chen Z, Ma X, Yang X, Zhang J and Jiang Z: In vitro evaluation of swine-derived Lactobacillus reuteri: Probiotic properties and effects on intestinal porcine epithelial cells challenged with enterotoxigenic Escherichia coli K88. J Microbiol Biotechnol. 26:1018–1025. 2016. View Article : Google Scholar : PubMed/NCBI

132 

Gu MJ, Song SK, Lee IK, Ko S, Han SE, Bae S, Ji SY, Park BC, Song KD, Lee HK, et al: Barrier protection via Toll-like receptor 2 signaling in porcine intestinal epithelial cells damaged by deoxynivalnol. Vet Res. 47:252016. View Article : Google Scholar : PubMed/NCBI

133 

Yang F, Wang A, Zeng X, Hou C, Liu H and Qiao S: Lactobacillus reuteri I5007 modulates tight junction protein expression in IPEC-J2 cells with LPS stimulation and in newborn piglets under normal conditions. BMC Microbiol. 15:322015. View Article : Google Scholar : PubMed/NCBI

134 

Kim SH, Jeung W, Choi ID, Jeong JW, Lee DE, Huh CS, Kim GB, Hong SS, Shim JJ, Lee JL, et al: Lactic acid bacteria improves Peyer's patch cell-mediated immunoglobulin A and tight-junction expression in a destructed gut microbial environment. J Microbiol Biotechnol. 26:1035–1045. 2016. View Article : Google Scholar : PubMed/NCBI

135 

Zhao Q and Elson CO: Adaptive immune education by gut microbiota antigens. Immunology. 154:28–37. 2018. View Article : Google Scholar : PubMed/NCBI

136 

Koboziev I, Webb CR, Furr KL and Grisham MB: Role of the enteric microbiota in intestinal homeostasis and inflammation. Free Radic Biol Med. 68:122–133. 2014. View Article : Google Scholar : PubMed/NCBI

137 

Maldonado Galdeano C, Cazorla SI, Lemme Dumit JM, Vélez E and Perdigón G: Beneficial effects of probiotic consumption on the immune system. Ann Nutr Metab. 74:115–124. 2019. View Article : Google Scholar : PubMed/NCBI

138 

Foo NP, Ou Yang H, Chiu HH, Chan HY, Liao CC, Yu CK and Wang YJ: Probiotics prevent the development of 1, 2-dimethylhydrazine (DMH)-induced colonic tumorigenesis through suppressed colonic mucosa cellular proliferation and increased stimulation of macrophages. J Agric Food Chem. 59:13337–13345. 2011. View Article : Google Scholar : PubMed/NCBI

139 

Foey A, Habil N, Strachan A and Beal J: Lacticaseibacillus casei strain shirota modulates macrophage-intestinal epithelial cell co-culture barrier integrity, bacterial sensing and inflammatory cytokines. Microorganisms. 10:20872022. View Article : Google Scholar : PubMed/NCBI

140 

Wong WY, Chan BD, Sham TT, Lee MM, Chan CO, Chau CT, Mok DK, Kwan YW and Tai WC: Lactobacillus casei strain shirota ameliorates dextran sulfate sodium-induced colitis in mice by increasing taurine-conjugated bile acids and inhibiting NF-κB signaling via stabilization of IκBα. Front Nutr. 9:8168362022. View Article : Google Scholar : PubMed/NCBI

141 

Santiago-López L, Hernández-Mendoza A, Vallejo-Cordoba B, Mata-Haro V, Wall-Medrano A and González-Córdova AF: Milk fermented with lactobacillus fermentum ameliorates indomethacin-induced intestinal inflammation: An exploratory study. Nutrients. 11:16102019. View Article : Google Scholar : PubMed/NCBI

142 

Muscari I, Fierabracci A, Adorisio S, Moretti M, Cannarile L, Thi Minh Hong V, Ayroldi E and Delfino DV: Glucocorticoids and natural killer cells: A suppressive relationship. Biochem Pharmacol. 198:1149302022. View Article : Google Scholar : PubMed/NCBI

143 

Fotiadis CI, Stoidis CN, Spyropoulos BG and Zografos ED: Role of probiotics, prebiotics and synbiotics in chemoprevention for colorectal cancer. World J Gastroenterol. 14:6453–6457. 2008. View Article : Google Scholar : PubMed/NCBI

144 

Rossi M, Keshavarzian A and Bishehsari F: Nutraceuticals in colorectal cancer: A mechanistic approach. Eur J Pharmacol. 833:396–402. 2018. View Article : Google Scholar : PubMed/NCBI

145 

El-Deeb NM, Yassin AM, Al-Madboly LA and El-Hawiet A: A novel purified Lactobacillus acidophilus 20079 exopolysaccharide, LA-EPS-20079, molecularly regulates both apoptotic and NF-κB inflammatory pathways in human colon cancer. Microb Cell Fact. 17:292018. View Article : Google Scholar : PubMed/NCBI

146 

Shi Y, Meng L, Zhang C, Zhang F and Fang Y: Extracellular vesicles of Lacticaseibacillus paracasei PC-H1 induce colorectal cancer cells apoptosis via PDK1/AKT/Bcl-2 signaling pathway. Microbiol Res. 255:1269212021. View Article : Google Scholar : PubMed/NCBI

147 

Jin K, Qian C, Lin J and Liu B: Cyclooxygenase-2-Prostaglandin E2 pathway: A key player in tumor-associated immune cells. Front Oncol. 13:10998112023. View Article : Google Scholar : PubMed/NCBI

148 

Kang YJ, Jang JY, Kwon YH, Lee JH, Lee S, Park Y, Jung YS, Im E, Moon HR, Chung HY and Kim ND: MHY2245, a sirtuin inhibitor, induces cell cycle arrest and apoptosis in HCT116 human colorectal cancer cells. Int J Mol Sci. 23:15902022. View Article : Google Scholar : PubMed/NCBI

149 

Artale S, Grillo N, Lepori S, Butti C, Bovio A, Barzaghi S, Colombo A, Castiglioni E, Barbarini L, Zanlorenzi L, et al: A nutritional approach for the management of chemotherapy-induced diarrhea in patients with colorectal cancer. Nutrients. 14:18012022. View Article : Google Scholar : PubMed/NCBI

150 

Burns AJ and Rowland IR: Antigenotoxicity of probiotics and prebiotics on faecal water-induced DNA damage in human colon adenocarcinoma cells. Mutat Res. 551:233–243. 2004. View Article : Google Scholar : PubMed/NCBI

151 

Pop OL, Suharoschi R and Gabbianelli R: Biodetoxification and protective properties of probiotics. Microorganisms. 10:12782022. View Article : Google Scholar : PubMed/NCBI

152 

Zhang XB and Ohta Y: Binding of mutagens by fractions of the cell wall skeleton of lactic acid bacteria on mutagens. J Dairy Sci. 74:1477–1481. 1991. View Article : Google Scholar : PubMed/NCBI

153 

Shao X, Xu B, Chen C, Li P and Luo H: The function and mechanism of lactic acid bacteria in the reduction of toxic substances in food: A review. Crit Rev Food Sci Nutr. 62:5950–5963. 2022. View Article : Google Scholar : PubMed/NCBI

154 

Nowak A and Libudzisz Z: Ability of probiotic Lactobacillus casei DN 114001 to bind or/and metabolise heterocyclic aromatic amines in vitro. Eur J Nutr. 48:419–427. 2009. View Article : Google Scholar : PubMed/NCBI

155 

Terahara M, Meguro S and Kaneko T: Effects of lactic acid bacteria on binding and absorption of mutagenic heterocyclic amines. Biosci Biotechnol Biochem. 62:197–200. 1998. View Article : Google Scholar : PubMed/NCBI

156 

Orrhage K, Sillerström E, Gustafsson JA, Nord CE and Rafter J: Binding of mutagenic heterocyclic amines by intestinal and lactic acid bacteria. Mutat Res. 311:239–248. 1994. View Article : Google Scholar : PubMed/NCBI

157 

Lázaro Á, Vila-Donat P and Manyes L: Emerging mycotoxins and preventive strategies related to gut microbiota changes: Probiotics, prebiotics, and postbiotics-a systematic review. Food Funct. 15:8998–9023. 2024. View Article : Google Scholar : PubMed/NCBI

158 

Liu L, Xie M and Wei D: Biological detoxification of mycotoxins: Current status and future advances. Int J Mol Sci. 23:10642022. View Article : Google Scholar : PubMed/NCBI

159 

Cuevas-González PF, González-Córdova AF, Vallejo-Cordoba B, Aguilar-Toalá JE, Hall FG, Urbizo-Reyes UC, Liceaga AM, Hernandez-Mendoza A and García HS: Protective role of lactic acid bacteria and yeasts as dietary carcinogen-binding agents-a review. Crit Rev Food Sci Nutr. 62:160–180. 2022. View Article : Google Scholar : PubMed/NCBI

160 

El-Nezami HS, Chrevatidis A, Auriola S, Salminen S and Mykkänen H: Removal of common fusarium toxins in vitro by strains of lactobacillus and propionibacterium. Food Addit Contam. 19:680–686. 2002. View Article : Google Scholar : PubMed/NCBI

161 

Zoghi A, Khosravi-Darani K and Sohrabvandi S: Surface binding of toxins and heavy metals by probiotics. Mini Rev Med Chem. 14:84–98. 2014. View Article : Google Scholar : PubMed/NCBI

162 

Massoud R and Zoghi A: Potential probiotic strains with heavy metals and mycotoxins bioremoval capacity for application in foodstuffs. J Appl Microbiol. 133:1288–1307. 2022. View Article : Google Scholar : PubMed/NCBI

163 

Lopez J and Tait SW: Mitochondrial apoptosis: Killing cancer using the enemy within. Br J Cancer. 112:957–962. 2015. View Article : Google Scholar : PubMed/NCBI

164 

Su S, Chhabra G, Singh CK, Ndiaye MA and Ahmad N: PLK1 inhibition-based combination therapies for cancer management. Transl Oncol. 16:1013322022. View Article : Google Scholar : PubMed/NCBI

165 

Sankarapandian V, Venmathi Maran BA, Rajendran RL, Jogalekar MP, Gurunagarajan S, Krishnamoorthy R, Gangadaran P and Ahn BC: An update on the effectiveness of probiotics in the prevention and treatment of cancer. Life (Basel). 12:592022.PubMed/NCBI

166 

Elmore S: Apoptosis: A review of programmed cell death. Toxicol Pathol. 35:495–516. 2007. View Article : Google Scholar : PubMed/NCBI

167 

Kiraz Y, Adan A, Kartal Yandim M and Baran Y: Major apoptotic mechanisms and genes involved in apoptosis. Tumour Biol. 37:8471–8486. 2016. View Article : Google Scholar : PubMed/NCBI

168 

Chen HH, Luo CW, Chen YL, Chiang JY, Huang CR, Wang YT, Chen CH, Guo J and Yip HK: Probiotic-facilitated cytokine-induced killer cells suppress peritoneal carcinomatosis and liver metastasis in colorectal cancer cells. Int J Biol Sci. 20:6162–6180. 2024. View Article : Google Scholar : PubMed/NCBI

169 

Karimi Ardestani S, Tafvizi F and Tajabadi Ebrahimi M: Heat-killed probiotic bacteria induce apoptosis of HT-29 human colon adenocarcinoma cell line via the regulation of Bax/Bcl2 and caspases pathway. Hum Exp Toxicol. 38:1069–1081. 2019. View Article : Google Scholar : PubMed/NCBI

170 

Baghbani-Arani F, Asgary V and Hashemi A: Cell-free extracts of Lactobacillus acidophilus and Lactobacillus delbrueckii display antiproliferative and antioxidant activities against HT-29 cell line. Nutr Cancer. 72:1390–1399. 2020. View Article : Google Scholar : PubMed/NCBI

171 

Cotter PD, Ross RP and Hill C: Bacteriocins-a viable alternative to antibiotics? Nat Rev Microbiol. 11:95–105. 2013. View Article : Google Scholar : PubMed/NCBI

172 

Konishi H, Fujiya M, Tanaka H, Ueno N, Moriichi K, Sasajima J, Ikuta K, Akutsu H, Tanabe H and Kohgo Y: Probiotic-derived ferrichrome inhibits colon cancer progression via JNK-mediated apoptosis. Nat Commun. 7:123652016. View Article : Google Scholar : PubMed/NCBI

173 

Thirabunyanon M, Boonprasom P and Niamsup P: Probiotic potential of lactic acid bacteria isolated from fermented dairy milks on antiproliferation of colon cancer cells. Biotechnol Lett. 31:571–576. 2009. View Article : Google Scholar : PubMed/NCBI

174 

Khosrovan Z, Haghighat S and Mahdavi M: The probiotic bacteria induce apoptosis in breast and colon cancer cells: An immunostimulatory effect. Immunoregulation. 3:37–50. 2020. View Article : Google Scholar

175 

Alshuail N, Alehaideb Z, Alghamdi S, Suliman R, Al-Eidi H, Ali R, Barhoumi T, Almutairi M, Alwhibi M, Alghanem B, et al: Achillea fragrantissima (Forssk.) Sch.Bip flower dichloromethane extract exerts anti-proliferative and pro-apoptotic properties in human triple-negative breast cancer (MDA-MB-231) cells: In vitro and in silico studies. Pharmaceuticals (Basel). 15:10602022. View Article : Google Scholar : PubMed/NCBI

176 

Asoudeh-Fard A, Barzegari A, Dehnad A, Bastani S, Golchin A and Omidi Y: Lactobacillus plantarum induces apoptosis in oral cancer KB cells through upregulation of PTEN and downregulation of MAPK signalling pathways. Bioimpacts. 7:193–198. 2017. View Article : Google Scholar : PubMed/NCBI

177 

Isazadeh A, Hajazimian S, Shadman B, Safaei S, Bedoustani AB, Chavoshi R, Shanehbandi D, Mashayekhi M, Nahaei M and Baradaran B: Anti-cancer effects of probiotic lactobacillus acidophilus for colorectal cancer cell line caco-2 through apoptosis induction. Pharm Sci. 27:262–267. 2021. View Article : Google Scholar

178 

Yavari M and Ahmadizadeh C: Effect of the cellular extract of co-cultured lactobacillus casei on BAX and Human β-Defensin 2 genes expression in HT29 cells. Intern Med Today. 26:364–381. 2020.

179 

Małaczewska J and Kaczorek-Łukowska E: Nisin-A lantibiotic with immunomodulatory properties: A review. Peptides. 137:1704792021. View Article : Google Scholar : PubMed/NCBI

180 

Singh A, Alexander SG and Martin S: Gut microbiome homeostasis and the future of probiotics in cancer immunotherapy. Front Immunol. 14:11144992023. View Article : Google Scholar : PubMed/NCBI

181 

Liu YC, Wu CR and Huang TW: Preventive effect of probiotics on oral mucositis induced by cancer treatment: A systematic review and meta-analysis. Int J Mol Sci. 23:132682022. View Article : Google Scholar : PubMed/NCBI

182 

Nazir Y, Hussain SA, Abdul Hamid A and Song Y: Probiotics and their potential preventive and therapeutic role for cancer, high serum cholesterol, and allergic and HIV diseases. Biomed Res Int. 2018:34284372018. View Article : Google Scholar : PubMed/NCBI

183 

Arora M, Baldi A, Kapila N, Bhandari S and Jeet K: Impact of probiotics and prebiotics on colon cancer: Mechanistic insights and future approaches. Curr Cancer Ther Rev. 15:27–36. 2019. View Article : Google Scholar

184 

Hou H, Chen D, Zhang K, Zhang W, Liu T, Wang S, Dai X, Wang B, Zhong W and Cao H: Gut microbiota-derived short-chain fatty acids and colorectal cancer: Ready for clinical translation? Cancer Lett. 526:225–235. 2022. View Article : Google Scholar : PubMed/NCBI

185 

Zhang S, Wang H and Zhu MJ: A sensitive GC/MS detection method for analyzing microbial metabolites short chain fatty acids in fecal and serum samples. Talanta. 196:249–254. 2019. View Article : Google Scholar : PubMed/NCBI

186 

Wong JM, De Souza R, Kendall CW, Emam A and Jenkins DJ: Colonic health: Fermentation and short chain fatty acids. J Clin Gastroenterol. 40:235–243. 2006. View Article : Google Scholar : PubMed/NCBI

187 

Bhogoju S and Nahashon S: Recent advances in probiotic application in animal health and nutrition: A review. Agriculture. 12:3042022. View Article : Google Scholar

188 

Encarnação JC, Abrantes AM, Pires AS and Botelho MF: Revisit dietary fiber on colorectal cancer: Butyrate and its role on prevention and treatment. Cancer Metastasis Rev. 34:465–478. 2015. View Article : Google Scholar : PubMed/NCBI

189 

Liu Q, Yu Z, Tian F, Zhao J, Zhang H, Zhai Q and Chen W: Surface components and metabolites of probiotics for regulation of intestinal epithelial barrier. Microb Cell Fact. 19:232020. View Article : Google Scholar : PubMed/NCBI

190 

Lu SY, Liu Y, Tang S, Zhang W, Yu Q, Shi C and Cheong KL: Gracilaria lemaneiformis polysaccharides alleviate colitis by modulating the gut microbiota and intestinal barrier in mice. Food Chem X. 13:1001972022. View Article : Google Scholar : PubMed/NCBI

191 

Ratajczak W, Rył A, Mizerski A, Walczakiewicz K, Sipak O and Laszczyńska M: Immunomodulatory potential of gut microbiome-derived short-chain fatty acids (SCFAs). Acta Biochim Pol. 66:1–12. 2019.PubMed/NCBI

192 

Yoo JY, Groer M, Dutra SVO, Sarkar A and McSkimming DI: Gut microbiota and immune system interactions. Microorganisms. 8:15872020. View Article : Google Scholar : PubMed/NCBI

193 

Woo V and Alenghat T: Epigenetic regulation by gut microbiota. Gut Microbes. 14:20224072022. View Article : Google Scholar : PubMed/NCBI

194 

Ruzic D, Djoković N, Srdić-Rajić T, Echeverria C, Nikolic K and Santibanez JF: Targeting histone deacetylases: Opportunities for cancer treatment and chemoprevention. Pharmaceutics. 14:2092022. View Article : Google Scholar : PubMed/NCBI

195 

Faghfoori Z, Gargari BP, Gharamaleki AS, Bagherpour H and Khosroushahi AY: Cellular and molecular mechanisms of probiotics effects on colorectal cancer. J Funct Foods. 18:463–472. 2015. View Article : Google Scholar

196 

Sanaei M and Kavoosi F: Effect of sodium butyrate on p16INK4a, p14ARF, p15INK4b, Class I HDACs (HDACs 1, 2, 3) Class II HDACs (HDACs 4, 5, 6), Cell growth inhibition and apoptosis induction in pancreatic cancer AsPC-1 and colon cancer HCT-116 cell lines. Asian Pac J Cancer Prev. 23:795–802. 2022. View Article : Google Scholar : PubMed/NCBI

197 

Chai L, Luo Q, Cai K, Wang K and Xu B: Reduced fecal short-chain fatty acids levels and the relationship with gut microbiota in IgA nephropathy. BMC Nephrol. 22:2092021. View Article : Google Scholar : PubMed/NCBI

198 

Piotrowska M, Binienda A and Fichna J: The role of fatty acids in Crohn's disease pathophysiology-An overview. Mol Cell Endocrinol. 538:1114482021. View Article : Google Scholar : PubMed/NCBI

199 

Haase S, Haghikia A, Wilck N, Müller DN and Linker RA: Impacts of microbiome metabolites on immune regulation and autoimmunity. Immunology. 154:230–238. 2018. View Article : Google Scholar : PubMed/NCBI

200 

Ni D, Tan J, Niewold P, Spiteri AG, Pinget GV, Stanley D, King NJC and Macia L: Impact of dietary fiber on west nile virus infection. Front Immunol. 13:7844862022. View Article : Google Scholar : PubMed/NCBI

201 

Shanmugam G, Rakshit S and Sarkar K: HDAC inhibitors: Targets for tumor therapy, immune modulation and lung diseases. Transl Oncol. 16:1013122022. View Article : Google Scholar : PubMed/NCBI

202 

Lee SY, Kang JH, Kim JH, Jeong JW, Kim HW, Oh DH, Yoon SH and Hur SJ: Relationship between gut microbiota and colorectal cancer: Probiotics as a potential strategy for prevention. Food Res Int. 156:1113272022. View Article : Google Scholar : PubMed/NCBI

203 

Althagafi HA: The potential anticancer potency of kolaviron on colorectal adenocarcinoma (Caco-2) cells. Anticancer Agents Med Chem. 24:1097–1108. 2024. View Article : Google Scholar : PubMed/NCBI

204 

Jiang X, Li S, Qiu X, Cong J, Zhou J and Miu W: Curcumin inhibits cell viability and increases apoptosis of SW620 human colon adenocarcinoma cells via the caudal type homeobox-2 (CDX2)/Wnt/β-catenin pathway. Med Sci Monit. 25:7451–7458. 2019. View Article : Google Scholar : PubMed/NCBI

205 

Huang C, Deng W, Xu HZ, Zhou C, Zhang F, Chen J, Bao Q, Zhou X, Liu M, Li J and Liu C: Short-chain fatty acids reprogram metabolic profiles with the induction of reactive oxygen species production in human colorectal adenocarcinoma cells. Comput Struct Biotechnol J. 21:1606–1620. 2023. View Article : Google Scholar : PubMed/NCBI

206 

Zeng H, Hamlin SK, Safratowich BD, Cheng WH and Johnson LK: Superior inhibitory efficacy of butyrate over propionate and acetate against human colon cancer cell proliferation via cell cycle arrest and apoptosis: Linking dietary fiber to cancer prevention. Nutr Res. 83:63–72. 2020. View Article : Google Scholar : PubMed/NCBI

207 

Aziz T, Sarwar A, Daudzai Z, Naseeb J, Din JU, Aftab U, Saidal A, Ghani M, Khan AA, Naz S, et al: Conjugated fatty acids (CFAS) production via various bacterial strains and their applications. A review. J Chil Chem Soc. 67:5445–5452. 2022. View Article : Google Scholar

208 

Wu C, Chen H, Mei Y, Yang B, Zhao J, Stanton C and Chen W: Advances in research on microbial conjugated linoleic acid bioconversion. Prog Lipid Res. 93:1012572024. View Article : Google Scholar : PubMed/NCBI

209 

Liu XX, Zhang HY, Song X, Yang Y, Xiong ZQ, Xia YJ and Ai LZ: Reasons for the differences in biotransformation of conjugated linoleic acid by Lactobacillus plantarum. J Dairy Sci. 104:11466–11473. 2021. View Article : Google Scholar : PubMed/NCBI

210 

Qian Y, Chun ZJ, Liu ZY and Xu L: Probiotics in gastrointestinal cancer: Antitumoral effects and molecular mechanisms of action. Zhonghua Nei Ke Za Zhi. 61:1167–1171. 2022.(In Chinese). PubMed/NCBI

211 

Cho HJ, Kim WK, Kim EJ, Jung KC, Park S, Lee HS, Tyner AL and Park JH: Conjugated linoleic acid inhibits cell proliferation and ErbB3 signaling in HT-29 human colon cell line. Am J Physiol Gastrointest Liver Physiol. 284:G996–G1005. 2003. View Article : Google Scholar : PubMed/NCBI

212 

Chen Y, Ma W, Zhao J, Stanton C, Ross RP, Zhang H, Chen W and Yang B: Lactobacillus plantarum ameliorates colorectal cancer by ameliorating the intestinal barrier through the CLA-PPAR-γ axis. J Agric Food Chem. 72:19766–19785. 2024. View Article : Google Scholar : PubMed/NCBI

213 

Dachev M, Bryndová J, Jakubek M, Moučka Z and Urban M: The effects of conjugated linoleic acids on cancer. Processes. 9:4542021. View Article : Google Scholar

214 

Shahzad MMK, Felder M, Ludwig K, Van Galder HR, Anderson ML, Kim J, Cook ME, Kapur AK and Patankar MS: Trans10, cis12 conjugated linoleic acid inhibits proliferation and migration of ovarian cancer cells by inducing ER stress, autophagy, and modulation of Src. PLoS One. 13:e01895242018. View Article : Google Scholar : PubMed/NCBI

215 

Badawy S, Liu Y, Guo M, Liu Z, Xie C, Marawan MA, Ares I, Lopez-Torres B, Martínez M, Maximiliano JE, et al: Conjugated linoleic acid (CLA) as a functional food: Is it beneficial or not? Food Res Int. 172:1131582023. View Article : Google Scholar : PubMed/NCBI

216 

Saber A, Alipour B, Faghfoori Z and Yari Khosroushahi A: Cellular and molecular effects of yeast probiotics on cancer. Crit Rev Microbiol. 43:96–115. 2017. View Article : Google Scholar : PubMed/NCBI

217 

Basak S and Duttaroy AK: Conjugated linoleic acid and its beneficial effects in obesity, cardiovascular disease, and cancer. Nutrients. 12:19132020. View Article : Google Scholar : PubMed/NCBI

218 

Mei Y, Chen H, Yang B, Zhao J, Zhang H and Chen W: Research progress on conjugated linoleic acid bio-conversion in Bifidobacterium. Int J Food Microbiol. 369:1095932022. View Article : Google Scholar : PubMed/NCBI

219 

Chen Y, Yang B, Ross RP, Jin Y, Stanton C, Zhao J, Zhang H and Chen W: Orally administered CLA ameliorates DSS-induced colitis in mice via intestinal barrier improvement, oxidative stress reduction, and inflammatory cytokine and gut microbiota modulation. J Agric Food Chem. 67:13282–13298. 2019. View Article : Google Scholar : PubMed/NCBI

220 

Cruz BCS, Sarandy MM, Messias AC, Gonçalves RV, Ferreira CLLF and Peluzio MCG: Preclinical and clinical relevance of probiotics and synbiotics in colorectal carcinogenesis: A systematic review. Nutr Rev. 78:667–687. 2020. View Article : Google Scholar : PubMed/NCBI

221 

Żółkiewicz J, Marzec A, Ruszczyński M and Feleszko W: Postbiotics-A step beyond pre- and probiotics. Nutrients. 12:21892020. View Article : Google Scholar : PubMed/NCBI

222 

Chen P, Yang C, Ren K, Xu M, Pan C, Ye X and Li L: Modulation of gut microbiota by probiotics to improve the efficacy of immunotherapy in hepatocellular carcinoma. Front Immunol. 15:15049482024. View Article : Google Scholar : PubMed/NCBI

223 

De Souza JB, Brelaz-de-Castro MCA and Cavalcanti IMF: Strategies for the treatment of colorectal cancer caused by gut microbiota. Life Sci. 290:1202022022. View Article : Google Scholar : PubMed/NCBI

224 

Wang P, Jia Y, Wu R, Chen Z and Yan R: Human gut bacterial β-glucuronidase inhibition: An emerging approach to manage medication therapy. Biochem Pharmacol. 190:1145662021. View Article : Google Scholar : PubMed/NCBI

225 

Josephy PD and Allen-Vercoe E: Reductive metabolism of azo dyes and drugs: Toxicological implications. Food Chem Toxicol. 178:1139322023. View Article : Google Scholar : PubMed/NCBI

226 

Molska M and Reguła J: Potential mechanisms of probiotics action in the prevention and treatment of colorectal cancer. Nutrients. 11:24532019. View Article : Google Scholar : PubMed/NCBI

227 

Nowak A, Paliwoda A and Błasiak J: Anti-proliferative, pro-apoptotic and anti-oxidative activity of Lactobacillus and Bifidobacterium strains: A review of mechanisms and therapeutic perspectives. Crit Rev Food Sci Nutr. 59:3456–3467. 2019. View Article : Google Scholar : PubMed/NCBI

228 

De Roos NM and Katan MB: Effects of probiotic bacteria on diarrhea, lipid metabolism, and carcinogenesis: A review of papers published between 1988 and 1998. Am J Clin Nutr. 71:405–411. 2000. View Article : Google Scholar : PubMed/NCBI

229 

Jacquier EF, van de Wouw M, Nekrasov E, Contractor N, Kassis A and Marcu D: Local and systemic effects of bioactive food ingredients: Is there a role for functional foods to prime the gut for resilience? Foods. 13:7392024. View Article : Google Scholar : PubMed/NCBI

230 

Phannasorn W, Pharapirom A, Thiennimitr P, Guo H, Ketnawa S and Wongpoomchai R: Enriched riceberry bran oil exerts chemopreventive properties through anti-inflammation and alteration of gut microbiota in carcinogen-induced liver and colon carcinogenesis in rats. Cancers (Basel). 14:43582022. View Article : Google Scholar : PubMed/NCBI

231 

Walia S, Kamal R, Kanwar SS and Dhawan DK: Hepato-protective role of chemo-preventive probiotics during DMH-induced CRC in rats. J Biochem Mol Toxicol. 35:e227882021. View Article : Google Scholar : PubMed/NCBI

232 

Vougiouklaki D, Tsironi T, Tsantes AG, Tsakali E, Van Impe JFM and Houhoula D: Probiotic properties and antioxidant activity in vitro of lactic acid bacteria. Microorganisms. 11:12642023. View Article : Google Scholar : PubMed/NCBI

233 

Guo Y, Huang R, Niu Y, Zhang P, Li Y and Zhang W: Chemical characteristics, antioxidant capacity, bacterial community, and metabolite composition of mulberry silage ensiling with lactic acid bacteria. Front Microbiol. 15:13632562024. View Article : Google Scholar : PubMed/NCBI

234 

Mobasherpour P, Yavarmanesh M and Edalatian Dovom MR: Antitumor properties of traditional lactic acid bacteria: Short-chain fatty acid production and interleukin 12 induction. Heliyon. 10:e361832024. View Article : Google Scholar : PubMed/NCBI

235 

Tang C and Lu Z: Health promoting activities of probiotics. J Food Biochem. 43:e129442019. View Article : Google Scholar : PubMed/NCBI

236 

Martínez FG, Cuencas Barrientos ME, Mozzi F and Pescuma M: Survival of selenium-enriched lactic acid bacteria in a fermented drink under storage and simulated gastro-intestinal digestion. Food Res Int. 123:115–124. 2019. View Article : Google Scholar : PubMed/NCBI

237 

Tsivileva O, Shaternikov A and Evseeva N: Basidiomycetes polysaccharides regulate growth and antioxidant defense system in wheat. Int J Mol Sci. 25:68772024. View Article : Google Scholar : PubMed/NCBI

238 

Salimi F and Farrokh P: Recent advances in the biological activities of microbial exopolysaccharides. World J Microbiol Biotechnol. 39:2132023. View Article : Google Scholar : PubMed/NCBI

239 

Zhang J, Xiao Y, Wang H, Zhang H, Chen W and Lu W: Lactic acid bacteria-derived exopolysaccharide: Formation, immunomodulatory ability, health effects, and structure-function relationship. Microbiol Res. 274:1274322023. View Article : Google Scholar : PubMed/NCBI

240 

Adesulu-Dahunsi AT, Sanni AI and Jeyaram K: Production, characterization and in vitro antioxidant activities of exopolysaccharide from Weissella cibaria GA44. LWT. 87:432–442. 2018. View Article : Google Scholar

241 

Dougherty MW and Jobin C: Intestinal bacteria and colorectal cancer: Etiology and treatment. Gut Microbes. 15:21850282023. View Article : Google Scholar : PubMed/NCBI

242 

Kang X, Liu C, Ding Y, Ni Y, Ji F, Lau HCH, Jiang L, Sung JJ, Wong SH and Yu J: Roseburia intestinalis generated butyrate boosts anti-PD-1 efficacy in colorectal cancer by activating cytotoxic CD8+ T cells. Gut. 72:2112–2122. 2023. View Article : Google Scholar : PubMed/NCBI

243 

Zhao J, Liao Y, Wei C, Ma Y, Wang F, Chen Y, Zhao B, Ji H, Wang D and Tang D: Potential ability of probiotics in the prevention and treatment of colorectal cancer. Clin Med Insights Oncol. 17:117955492311882252023. View Article : Google Scholar : PubMed/NCBI

244 

Jain S, Purohit A, Nema P, Vishwakarma H, Qureshi A and kumar JP: Pathways of targeted therapy for colorectal cancer. J Drug Delivery Ther. 12:217–221. 2022. View Article : Google Scholar

245 

Chrysostomou D, Roberts LA, Marchesi JR and Kinross JM: Gut Microbiota modulation of efficacy and toxicity of cancer chemotherapy and immunotherapy. Gastroenterology. 164:198–213. 2023. View Article : Google Scholar : PubMed/NCBI

246 

Lu L, Dong J, Liu Y, Qian Y, Zhang G, Zhou W, Zhao A, Ji G and Xu H: New insights into natural products that target the gut microbiota: Effects on the prevention and treatment of colorectal cancer. Front Pharmacol. 13:9647932022. View Article : Google Scholar : PubMed/NCBI

247 

Guo Y, Wang M, Zou Y, Jin L, Zhao Z, Liu Q, Wang S and Li J: Mechanisms of chemotherapeutic resistance and the application of targeted nanoparticles for enhanced chemotherapy in colorectal cancer. J Nanobiotechnology. 20:3712022. View Article : Google Scholar : PubMed/NCBI

248 

Kouidhi S, Zidi O, Belkhiria Z, Rais H, Ayadi A, Ben Ayed F, Mosbah A, Cherif A and El Gaaied ABA: Gut microbiota, an emergent target to shape the efficiency of cancer therapy. Explor Target Antitumor Ther. 4:240–265. 2023. View Article : Google Scholar : PubMed/NCBI

249 

Mahdy MS, Azmy AF, Dishisha T, Mohamed WR, Ahmed KA, Hassan A, Aidy SE and El-Gendy AO: Irinotecan-gut microbiota interactions and the capability of probiotics to mitigate Irinotecan-associated toxicity. BMC Microbiol. 23:532023. View Article : Google Scholar : PubMed/NCBI

250 

Ren Z, Chen S, Lv H, Peng L, Yang W, Chen J, Wu Z and Wan C: Effect of Bifidobacterium animalis subsp. lactis SF on enhancing the tumor suppression of irinotecan by regulating the intestinal flora. Pharmacol Res. 184:1064062022. View Article : Google Scholar : PubMed/NCBI

251 

Cai B, Pan J, Chen H, Chen X, Ye Z, Yuan H, Sun H and Wan P: Oyster polysaccharides ameliorate intestinal mucositis and improve metabolism in 5-fluorouracil-treated S180 tumour-bearing mice. Carbohydr Polym. 256:1175452021. View Article : Google Scholar : PubMed/NCBI

252 

Capurso L: Thirty years of Lactobacillus rhamnosus GG: A review. J Clin Gastroenterol. 53:S1–S41. 2019. View Article : Google Scholar : PubMed/NCBI

253 

He Y, Fu L, Li Y, Wang W, Gong M, Zhang J, Dong X, Huang J, Wang Q, Mackay CR, et al: Gut microbial metabolites facilitate anticancer therapy efficacy by modulating cytotoxic CD8+ T cell immunity. Cell Metab. 33:988–1000. e72021. View Article : Google Scholar : PubMed/NCBI

254 

He Y, Ling Y, Zhang Z, Mertens RT, Cao Q, Xu X, Guo K, Shi Q, Zhang X, Huo L, et al: Butyrate reverses ferroptosis resistance in colorectal cancer by inducing c-Fos-dependent xCT suppression. Redox Biol. 65:1028222023. View Article : Google Scholar : PubMed/NCBI

255 

Khorashadizadeh S, Abbasifar S, Yousefi M, Fayedeh F and Moodi Ghalibaf A: The role of microbiome and probiotics in chemo-radiotherapy-induced diarrhea: A narrative review of the current evidence. Cancer Rep (Hoboken). 7:e700292024. View Article : Google Scholar : PubMed/NCBI

256 

Moraitis I, Guiu J and Rubert J: Gut microbiota controlling radiation-induced enteritis and intestinal regeneration. Trends Endocrinol Metab. 34:489–501. 2023. View Article : Google Scholar : PubMed/NCBI

257 

Long L, Zhang Y, Zang J, Liu P, Liu W, Sun C, Tian D, Li P, Tian J and Xiao J: Investigating the relationship between postoperative radiotherapy and intestinal flora in rectal cancer patients: A study on efficacy and radiation enteritis. Front Oncol. 14:14084362024. View Article : Google Scholar : PubMed/NCBI

258 

Gonzalez-Mercado VJ, Henderson WA, Sarkar A, Lim J, Saligan LN, Berk L, Dishaw L, McMillan S, Groer M, Sepehri F and Melkus GD: Changes in gut microbiome associated with co-occurring symptoms development during chemo-radiation for rectal cancer: A proof of concept study. Biol Res Nurs. 23:31–41. 2021. View Article : Google Scholar : PubMed/NCBI

259 

Al-Qadami G, Van Sebille Y, Le H and Bowen J: Gut microbiota: implications for radiotherapy response and radiotherapy-induced mucositis. Expert Rev Gastroenterol Hepatol. 13:485–496. 2019. View Article : Google Scholar : PubMed/NCBI

260 

Sun CH, Li BB, Wang B, Zhao J, Zhang XY, Li TT, Li WB, Tang D, Qiu MJ, Wang XC, et al: The role of Fusobacterium nucleatum in colorectal cancer: From carcinogenesis to clinical management. Chronic Dis Transl Med. 5:178–187. 2019.PubMed/NCBI

261 

Jin Y, Wang J and Wang Y: Unraveling the complexity of radiotherapy- and chemotherapy-induced oral mucositis: Insights into pathogenesis and intervention strategies. Support Care Cancer. 33:1952025. View Article : Google Scholar : PubMed/NCBI

262 

Wang K, Zhang J, Zhang Y, Xue J, Wang H, Tan X, Jiao X and Jiang H: The recovery of intestinal barrier function and changes in oral microbiota after radiation therapy injury. Front Cell Infect Microbiol. 13:12886662024. View Article : Google Scholar : PubMed/NCBI

263 

Chen QY, Tian HL, Yang B, Lin ZL, Zhao D, Ye C, Zhang XY, Qin HL and Li N: Effect of intestinal preparation on the efficacy and safety of fecal microbiota transplantation treatment. Zhonghua Wei Chang Wai Ke Za Zhi. 23:48–55. 2020.(In Chinese). PubMed/NCBI

264 

Al Zein M, Boukhdoud M, Shammaa H, Mouslem H, El Ayoubi LM, Iratni R, Issa K, Khachab M, Assi HI, Sahebkar A and Eid AH: Immunotherapy and immunoevasion of colorectal cancer. Drug Discov Today. 28:1036692023. View Article : Google Scholar : PubMed/NCBI

265 

Sun BL: Current microsatellite instability testing in management of colorectal cancer. Clin Colorectal Cancer. 20:e12–e20. 2021. View Article : Google Scholar : PubMed/NCBI

266 

Guo R, Li J, Hu J, Fu Q, Yan Y, Xu S, Wang X and Jiao F: Combination of epidrugs with immune checkpoint inhibitors in cancer immunotherapy: From theory to therapy. Int Immunopharmacol. 120:1104172023. View Article : Google Scholar : PubMed/NCBI

267 

Salek Farrokhi A, Darabi N, Yousefi B, Askandar RH, Shariati M and Eslami M: Is it true that gut microbiota is considered as panacea in cancer therapy? J Cell Physiol. 234:14941–14950. 2019. View Article : Google Scholar : PubMed/NCBI

268 

Wu J, Wang S, Zheng B, Qiu X, Wang H and Chen L: Modulation of gut microbiota to enhance effect of checkpoint inhibitor immunotherapy. Front Immunol. 12:6691502021. View Article : Google Scholar : PubMed/NCBI

269 

Zhao H, Wang D, Zhang Z, Xian J and Bai X: Effect of gut microbiota-derived metabolites on immune checkpoint inhibitor therapy: Enemy or friend? Molecules. 27:47992022. View Article : Google Scholar : PubMed/NCBI

270 

Xie Y and Liu F: The role of the gut microbiota in tumor, immunity, and immunotherapy. Front Immunol. 15:14109282024. View Article : Google Scholar : PubMed/NCBI

271 

Aghamajidi A and Maleki Vareki S: The effect of the gut microbiota on systemic and anti-tumor immunity and response to systemic therapy against cancer. Cancers (Basel). 14:35632022. View Article : Google Scholar : PubMed/NCBI

272 

Yang J, Yang H and Li Y: The triple interactions between gut microbiota, mycobiota and host immunity. Crit Rev Food Sci Nutr. 63:11604–11624. 2023. View Article : Google Scholar : PubMed/NCBI

273 

Noguera-Fernández N, Candela-González J and Orenes-Piñero E: Probiotics, prebiotics, fecal microbiota transplantation, and dietary patterns in inflammatory bowel disease. Mol Nutr Food Res. 68:e24004292024. View Article : Google Scholar : PubMed/NCBI

274 

Yadegar A, Bar-Yoseph H, Monaghan TM, Pakpour S, Severino A, Kuijper EJ, Smits WK, Terveer EM, Neupane S, Nabavi-Rad A, et al: Fecal microbiota transplantation: Current challenges and future landscapes. Clin Microbiol Rev. 37:e00060222024. View Article : Google Scholar : PubMed/NCBI

275 

Selvamani S, Mehta V, Ali El Enshasy H, Thevarajoo S, El Adawi H, Zeini I, Pham K, Varzakas T and Abomoelak B: Efficacy of probiotics-based interventions as therapy for inflammatory bowel disease: A recent update. Saudi J Biol Sci. 29:3546–3567. 2022. View Article : Google Scholar : PubMed/NCBI

276 

Wang JW, Kuo CH, Kuo FC, Wang YK, Hsu WH, Yu FJ, Hu HM, Hsu PI, Wang JY and Wu DC: Fecal microbiota transplantation: Review and update. J Formos Med Assoc. 118 (Suppl 1):S23–S31. 2019. View Article : Google Scholar : PubMed/NCBI

277 

Yu H, Li XX, Han X, Chen BX, Zhang XH, Gao S, Xu DQ, Wang Y, Gao ZK, Yu L, et al: Fecal microbiota transplantation inhibits colorectal cancer progression: Reversing intestinal microbial dysbiosis to enhance anti-cancer immune responses. Front Microbiol. 14:11268082023. View Article : Google Scholar : PubMed/NCBI

278 

Chang CW, Lee HC, Li LH, Chiang Chiau JS, Wang TE, Chuang WH, Chen MJ, Wang HY, Shih SC, Liu CY, et al: Fecal microbiota transplantation prevents intestinal injury, upregulation of toll-like receptors, and 5-fluorouracil/oxaliplatin-induced toxicity in colorectal cancer. Int J Mol Sci. 21:3862020. View Article : Google Scholar : PubMed/NCBI

279 

Pi Y, Wu Y, Zhang X, Lu D, Han D, Zhao J, Zheng X, Zhang S, Ye H, Lian S, et al: Gut microbiota-derived ursodeoxycholic acid alleviates low birth weight-induced colonic inflammation by enhancing M2 macrophage polarization. Microbiome. 11:192023. View Article : Google Scholar : PubMed/NCBI

280 

Song Q, Gao Y, Liu K, Tang Y, Man Y and Wu H: Gut microbial and metabolomics profiles reveal the potential mechanism of fecal microbiota transplantation in modulating the progression of colitis-associated colorectal cancer in mice. J Transl Med. 22:10282024. View Article : Google Scholar : PubMed/NCBI

281 

Wu R, Xiong R, Li Y, Chen J and Yan R: Gut microbiome, metabolome, host immunity associated with inflammatory bowel disease and intervention of fecal microbiota transplantation. J Autoimmun. 141:1030622023. View Article : Google Scholar : PubMed/NCBI

282 

Xu H, Cao C, Ren Y, Weng S, Liu L, Guo C, Wang L, Han X, Ren J and Liu Z: Antitumor effects of fecal microbiota transplantation: Implications for microbiome modulation in cancer treatment. Front Immunol. 13:9494902022. View Article : Google Scholar : PubMed/NCBI

283 

Perillo F, Amoroso C, Strati F, Giuffrè MR, Díaz-Basabe A, Lattanzi G and Facciotti F: Gut microbiota manipulation as a tool for colorectal cancer management: Recent advances in its use for therapeutic purposes. Int J Mol Sci. 21:53892020. View Article : Google Scholar : PubMed/NCBI

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May-2025
Volume 31 Issue 5

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Spandidos Publications style
Sun W, Ma S, Meng D, Wang C and Zhang J: Advances in research on the intestinal microbiota in the mechanism and prevention of colorectal cancer (Review). Mol Med Rep 31: 133, 2025.
APA
Sun, W., Ma, S., Meng, D., Wang, C., & Zhang, J. (2025). Advances in research on the intestinal microbiota in the mechanism and prevention of colorectal cancer (Review). Molecular Medicine Reports, 31, 133. https://doi.org/10.3892/mmr.2025.13498
MLA
Sun, W., Ma, S., Meng, D., Wang, C., Zhang, J."Advances in research on the intestinal microbiota in the mechanism and prevention of colorectal cancer (Review)". Molecular Medicine Reports 31.5 (2025): 133.
Chicago
Sun, W., Ma, S., Meng, D., Wang, C., Zhang, J."Advances in research on the intestinal microbiota in the mechanism and prevention of colorectal cancer (Review)". Molecular Medicine Reports 31, no. 5 (2025): 133. https://doi.org/10.3892/mmr.2025.13498