Gene expression profiling of the mouse gut: Effect of intestinal flora on intestinal health

Zhu,Wenhua; Li,Jun; Wu,Benyan

doi:10.3892/mmr.2017.8298

Gene expression profiling of the mouse gut: Effect of intestinal flora on intestinal health

Authors:
- Wenhua Zhu
- Jun Li
- Benyan Wu
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Affiliations: Department of Gastroenterology, South Building, Chinese PLA General Hospital, Beijing 100853, P.R. China
Published online on: December 18, 2017 https://doi.org/10.3892/mmr.2017.8298
Pages: 3667-3673
Copyright: © Zhu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The present study aimed to investigate the molecular mechanisms, including potential genes, pathways and interactions, underlying the effect of intestinal flora on intestinal health. The gene expression profiles of GSE22648 were downloaded from the Gene Expression Omnibus database to screen differentially expressed genes (DEGs). The Database for Annotation, Visualization and Integrated Discovery was used for Gene Ontology (GO) functional and pathway enrichment analysis of the DEGs. DEG‑associated literature was mined using the GenCLip 2.0 online tool. Finally, GO and pathway enrichment analyses of the DEGs in the literature were processed. By comparing microbiota‑depleted mouse samples and control mouse samples, a total of 115 DEGs, including 58 upregulated genes and 57 downregulated genes, were screened. The upregulated genes were enriched into various GO terms, including microsome, oxidation reduction and heme binding, whereas the 57 downregulated DEGs were enriched in different functions, including DNA packaging and linoleic acid metabolism. A total of 19 genes, including baculoviral IAP repeat containing 5, aurora kinase A, angiotensin I converting enzyme 2 and free fatty acid receptor 2 were identified and enriched in four modules, including cell division, chromosome segregation, inflammatory bowel disease and inflammatory response. AURKA, inner centromere protein antigens 135/155 kDa, baculoviral IAP repeat containing 5, aurora kinase B and solute carrier family 22 (organic cation/zwitterion transporter) member 4 were identified as potential important genes for intestinal flora and intestinal disease treatment through their involvement in various functions, including cell division, chromosome segregation, inflammatory bowel disease and inflammatory response.

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1	Abreu MT, Fukata M and Arditi M: TLR signaling in the gut in health and disease. J Immunol. 174:4453–4460. 2005. View Article : Google Scholar : PubMed/NCBI
2	Jeurissen SH, Lewis F, van der Klis JD, Mroz Z, Rebel JM and Ter Huurne AA: Parameters and techniques to determine intestinal health of poultry as constituted by immunity, integrity and functionality. Curr Issues Intest Microbiol. 3:1–14. 2002.PubMed/NCBI
3	Ott SJ, Musfeldt M, Wenderoth DF, Hampe J, Brant O, Fölsch UR, Timmis KN and Schreiber S: Reduction in diversity of the colonic mucosa associated bacterial microflora in patients with active inflammatory bowel disease. Gut. 53:685–693. 2004. View Article : Google Scholar : PubMed/NCBI
4	Round JL and Mazmanian SK: The gut microbiota shapes intestinal immune responses during health and disease. Nat Rev Immunol. 9:313–323. 2009. View Article : Google Scholar : PubMed/NCBI
5	Qin J, Li R, Raes J, Arumugam M, Burgdorf KS, Manichanh C, Nielsen T, Pons N, Levenez F, Yamada T, et al: A human gut microbial gene catalogue established by metagenomic sequencing. Nature. 464:59–65. 2010. View Article : Google Scholar : PubMed/NCBI
6	Guarner F and Malagelada JR: Gut flora in health and disease. Lancet. 361:512–519. 2003. View Article : Google Scholar : PubMed/NCBI
7	Jia ZY, Xia Y, Tong D, Yao J, Chen HQ and Yang J: Module-based functional pathway enrichment analysis of a protein-protein interaction network to study the effects of intestinal microbiota depletion in mice. Mol Med Rep. 9:2205–2212. 2014. View Article : Google Scholar : PubMed/NCBI
8	Smith AG, O'Doherty JV, Reilly P, Ryan MT, Bahar B and Sweeney T: The effects of laminarin derived from Laminaria digitata on measurements of gut health: Selected bacterial populations, intestinal fermentation, mucin gene expression and cytokine gene expression in the pig. Br J Nutr. 105:669–677. 2011. View Article : Google Scholar : PubMed/NCBI
9	Song M and Kellum JA: Interleukin-6. Crit Care Med. 33 12 Suppl:S463–S465. 2005. View Article : Google Scholar : PubMed/NCBI
10	Reikvam DH, Erofeev A, Sandvik A, Grcic V, Jahnsen FL, Gaustad P, McCoy KD, Macpherson AJ, Meza-Zepeda LA and Johansen FE: Depletion of murine intestinal microbiota: Effects on gut mucosa and epithelial gene expression. PLoS One. 6:e179962011. View Article : Google Scholar : PubMed/NCBI
11	Altman NS: An introduction to kernel and nearest-neighbor nonparametric regression. The American Statistician. 46:175–185. 1992. View Article : Google Scholar
12	Hastie T, Tibshirani R, Narasimhan B and Gilbert C: Impute: Imputation for microarray data. Bioinformatics. 17:520–525. 2001.PubMed/NCBI
13	Shabalin AA, Tjelmeland H, Fan C, Perou CM and Nobel AB: Merging two gene-expression studies via cross-platform normalization. Bioinformatics. 24:1154–1160. 2008. View Article : Google Scholar : PubMed/NCBI
14	Rudy J and Valafar F: Empirical comparison of cross-platform normalization methods for gene expression data. BMC Bioinformatics. 12:4672011. View Article : Google Scholar : PubMed/NCBI
15	Leek JT, Johnson WE, Parker HS, Fertig EJ, Jaffe AE, Zhang Y, Torres LC and Storey JD: sva: Surrogate Variable Analysis. R package version 3. 2013.
16	Wang JH, Zhao LF, Lin P, Su XR, Chen SJ, Huang LQ, Wang HF, Zhang H, Hu ZF, Yao KT and Huang ZX: GenCLiP 2.0: A web server for functional clustering of genes and construction of molecular networks based on free terms. Bioinformatics. 30:2534–2536. 2014. View Article : Google Scholar : PubMed/NCBI
17	Puupponen-Pimiä R, Aura AM, Oksman-Caldentey KM, Myllärinen P, Saarela M, Mattila-Sandholm T and Poutanen K: Development of functional ingredients for gut health. Trends Food Sci Technol. 13:3–11. 2002. View Article : Google Scholar
18	Pérez-Cobas AE, Gosalbes MJ, Friedrichs A, Knecht H, Artacho A, Eismann K, Otto W, Rojo D, Bargiela R, von Bergen M, et al: Gut microbiota disturbance during antibiotic therapy: A multi-omic approach. Gut. 62:1591–1601. 2013. View Article : Google Scholar : PubMed/NCBI
19	Barker N: Adult intestinal stem cells: Critical drivers of epithelial homeostasis and regeneration. Nat Rev Mol Cell Biol. 15:19–33. 2014. View Article : Google Scholar : PubMed/NCBI
20	Assimakopoulos SF, Tsamandas AC, Louvros E, Vagianos CE, Nikolopoulou VN, Thomopoulos KC, Charonis A and Scopa CD: Intestinal epithelial cell proliferation, apoptosis and expression of tight junction proteins in patients with obstructive jaundice. Eur J Clin Invest. 41:117–125. 2011. View Article : Google Scholar : PubMed/NCBI
21	Ding J, Swain JE and Smith GD: Aurora kinase-A regulates microtubule organizing center (MTOC) localization, chromosome dynamics, and histone-H3 phosphorylation in mouse oocytes. Mol Reprod Dev. 78:80–90. 2011. View Article : Google Scholar : PubMed/NCBI
22	Ratushny V, Pathak HB, Beeharry N, Tikhmyanova N, Xiao F, Li T, Litwin S, Connolly DC, Yen TJ, Weiner LM, et al: Dual inhibition of SRC and Aurora kinases induces postmitotic attachment defects and cell death. Oncogene. 31:1217–1227. 2012. View Article : Google Scholar : PubMed/NCBI
23	Nikonova AS, Astsaturov I, Serebriiskii IG, Dunbrack Jr RL and Golemis EA: Aurora A kinase (AURKA) in normal and pathological cell division. Cell Mol Life Sci. 70:661–687. 2013. View Article : Google Scholar : PubMed/NCBI
24	Shuda K, Schindler K, Ma J, Schultz RM and Donovan PJ: Aurora kinase B modulates chromosome alignment in mouse oocytes. Mol Reprod Dev. 76:1094–1105. 2009. View Article : Google Scholar : PubMed/NCBI
25	Fenton JI, Lavigne JA, Perkins SN, Liu H, Chandramouli GV, Shih JH, Hord NG and Hursting SD: Microarray analysis reveals that leptin induces autocrine/paracrine cascades to promote survival and proliferation of colon epithelial cells in an Apc genotype-dependent fashion. Mol carcinog. 47:9–21. 2008. View Article : Google Scholar : PubMed/NCBI
26	Felekkis K, Touvana E, Stefanou C and Deltas C: microRNAs: A newly described class of encoded molecules that play a role in health and disease. Hippokratia. 14:236–240. 2010.PubMed/NCBI
27	Vicario M, Martínez C and Santos J: Role of microRNA in IBS with increased gut permeability. Gut. 59:710–712. 2010. View Article : Google Scholar : PubMed/NCBI
28	Honda R, Körner R and Nigg EA: Exploring the functional interactions between Aurora B, INCENP, and survivin in mitosis. Mol Biol Cell. 14:3325–3341. 2003. View Article : Google Scholar : PubMed/NCBI
29	Guta FF, O'Tooleb P and Walsha MA: MS04 P01 Structural and functional studies of the probiotic organism Lactobacillus salivarius Mario Bumanna, Heinz. Acta Cryst. 63:s1272007. View Article : Google Scholar
30	Yang J, Zappacosta F, Annan RS, Nurse K, Tummino PJ, Copeland RA and Lai Z: The catalytic role of INCENP in Aurora B activation and the kinetic mechanism of Aurora B/INCENP. Biochem. J. 417:355–360. 2009.
31	Chang JL, Chen TH, Wang CF, Chiang YH, Huang YL, Wong FH, Chou CK and Chen CM: Borealin/Dasra B is a cell cycle-regulated chromosomal passenger protein and its nuclear accumulation is linked to poor prognosis for human gastric cancer. Exp Cell Res. 312:962–973. 2006. View Article : Google Scholar : PubMed/NCBI
32	Neufert C, Pickert G, Zheng Y, Wittkopf N, Warntjen M, Nikolaev A, Ouyang W, Neurath MF and Becker C: Activation of epithelial STAT3 regulates intestinal homeostasis. Cell Cycle. 9:652–655. 2010. View Article : Google Scholar : PubMed/NCBI
33	Hooper LV, Littman DR and Macpherson AJ: Interactions between the microbiota and the immune system. Science. 336:1268–1273. 2012. View Article : Google Scholar : PubMed/NCBI
34	Kamada N, Seo SU, Chen GY and Núñez G: Role of the gut microbiota in immunity and inflammatory disease. Nat Rev Immunol. 13:321–335. 2013. View Article : Google Scholar : PubMed/NCBI
35	Tremaroli V and Bäckhed F: Functional interactions between the gut microbiota and host metabolism. Nature. 489:242–249. 2012. View Article : Google Scholar : PubMed/NCBI
36	Shekhawat PS, Sonne S, Carter AL, Matern D and Ganapathy V: Enzymes involved in L-carnitine biosynthesis are expressed by small intestinal enterocytes in mice: Implications for gut health. J Crohns Colitis. 7:e197–e205. 2013. View Article : Google Scholar : PubMed/NCBI
37	Tokuhiro S, Yamada R, Chang X, Suzuki A, Kochi Y, Sawada T, Suzuki M, Nagasaki M, Ohtsuki M, Ono M, et al: An intronic SNP in a RUNX1 binding site of SLC22A4, encoding an organic cation transporter, is associated with rheumatoid arthritis. Nat Genet. 35:341–348. 2003. View Article : Google Scholar : PubMed/NCBI
38	Ferraris A, Torres B, Knafelz D, Barabino A, Lionetti P, de Angelis GL, Iacono G, Papadatou B, D'Amato G, Di Ciommo V, et al: Relationship between CARD15, SLC22A4/5 and DLG5 polymorphisms and early-onset inflammatory bowel diseases: An Italian multicentric study. Inflamm Bowel Dis. 12:355–361. 2006. View Article : Google Scholar : PubMed/NCBI
39	Kelly D, King T and Aminov R: Importance of microbial colonization of the gut in early life to the development of immunity. Mutat Res. 622:58–69. 2007. View Article : Google Scholar : PubMed/NCBI