Gut health of children with autism spectrum disorder

Kakabadze,Elene; Makalatia,Khatuna; Bakuradze,Nata; Grdzelishvili,Nino; Kereselidze,Sophie; Ediberidze,Tamar; Berulava,Veriko; Sabauri,Nana; Cholokashvili,Nana; Javakhishvili,Elene; Natroshvili,Gulnara; Tatrishvili,Tamar; Motsikulashvili,Mariam; Chanishvili,Nina; Abiatari,Ivane

doi:10.3892/wasj.2022.164

Gut health of children with autism spectrum disorder

Authors:
- Elene Kakabadze
- Khatuna Makalatia
- Nata Bakuradze
- Nino Grdzelishvili
- Sophie Kereselidze
- Tamar Ediberidze
- Veriko Berulava
- Nana Sabauri
- Nana Cholokashvili
- Elene Javakhishvili
- Gulnara Natroshvili
- Tamar Tatrishvili
- Mariam Motsikulashvili
- Nina Chanishvili
- Ivane Abiatari
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Affiliations: Research and Development Department, George Eliava Institute of Bacteriophages, Microbiology and Virology, 0160 Tbilisi, Georgia, School of Natural Sciences and Medicine, Ilia State University, 0162 Tbilisi, Georgia, Eliava Bacteriophage Analytical‑Diagnostic Centre, 0160 Tbilisi, Georgia
Published online on: July 14, 2022 https://doi.org/10.3892/wasj.2022.164
Article Number: 29
Copyright: © Kakabadze et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder, frequently manifested by gastrointestinal symptoms. The investigation of alterations in the gut microbiome and its role in the gut‑brain axis communication is a promising field that may aid in the understanding of ASD symptoms. The present study thus focused on a preliminary investigation of the diversity, presence and drug‑resistance of particular bacterial species in the gut microbiota of ASD and neurotypical children. The study was performed in a case‑control manner and the relevant information of the participants was collected using dedicated questionnaires. Stool samples were collected from urban residents and the differences in microbial communities between the study and control groups were investigated and compared using culture‑dependent methods. Since phages are considered as alternatives to antibiotics, as well as a promising tool for the re‑instatement of disturbed microbiotas, antibiotic resistance and phage susceptibility profiles of the isolated intestinal pathogens were defined simultaneously. As a result, antibiotic resistant and phage susceptible β‑haemolytic Escherichia coli, but no Clostridioides difficile were detected in the collected sample. The differences in intestinal health and gut microbiota between the study groups were minor. On the whole, the findings of the present study may provide the basis for an extended metagenomics study of microbiota in the ASD population.

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1	Essa MM and Qoronfleh MW (eds): Personalized food intervention and therapy for autism spectrum disorder management. Vol. 24. Springer Nature, 2020.
2	Wiśniowiecka-Kowalnik B and Nowakowska BA: Genetics and epigenetics of autism spectrum disorder-current evidence in the field. J Appl Genet. 60:37–47. 2019.PubMed/NCBI View Article : Google Scholar
3	Loomes R, Hull L and Mandy WPL: What is the male-to-female ratio in autism spectrum disorder? A systematic review and meta-analysis. J Am Acad Child Adolesc Psychiatry. 56:466–474. 2017.PubMed/NCBI View Article : Google Scholar
4	Fombonne E: Epidemiology of pervasive developmental disorders. Pediatr Res. 65:591–598. 2009.PubMed/NCBI View Article : Google Scholar
5	Baxter AJ, Brugha TS, Erskine HE, Scheurer RW, Vos T and Scott JG: The epidemiology and global burden of autism spectrum disorders. Psychol Med. 45:601–613. 2015.PubMed/NCBI View Article : Google Scholar
6	Global Research on Developmental Disabilities Collaborators. Developmental disabilities among children younger than 5 years in 195 countries and territories, 1990-2016: A systematic analysis for the global burden of disease study 2016. Lancet Glob Health. 6:e1100–e1121. 2018.PubMed/NCBI View Article : Google Scholar
7	Muhle RA, Reed HE, Stratigos KA and Veenstra-VanderWeele J: The emerging clinical neuroscience of autism spectrum disorder: A review. JAMA Psychiatry. 75:514–523. 2018.PubMed/NCBI View Article : Google Scholar
8	Oh D and Cheon KA: Alteration of gut microbiota in autism spectrum disorder: An overview. Soa Chongsonyon Chongsin Uihak. 31:131–145. 2020.PubMed/NCBI View Article : Google Scholar
9	Mayer EA, Padua D and Tillisch K: Altered brain-gut axis in autism: Comorbidity or causative mechanisms? Bioessays. 36:933–939. 2014.PubMed/NCBI View Article : Google Scholar
10	Fung TC: The microbiota-immune axis as a central mediator of gut-brain communication. Neurobiol Dis. 136(104714)2020.PubMed/NCBI View Article : Google Scholar
11	Sherwin E, Dinan TG and Cryan JF: Recent developments in understanding the role of the gut microbiota in brain health and disease. Ann N Y Acad Sci. 1420:5–25. 2018.PubMed/NCBI View Article : Google Scholar
12	Borre YE, O'Keeffe GW, Clarke G, Stanton C, Dinan TG and Cryan JF: Microbiota and neurodevelopmental windows: Implications for brain disorders. Trends Mol Med. 20:509–518. 2014.PubMed/NCBI View Article : Google Scholar
13	Fowlie G, Cohen N and Ming X: The perturbance of microbiome and gut-brain axis in autism spectrum disorders. Int J Mol Sci. 19(2251)2018.PubMed/NCBI View Article : Google Scholar
14	Esnafoglu E, Cırrık S, Ayyıldız SN, Erdil A, Ertürk EY, Daglı A and Noyan T: Increased serum zonulin levels as an intestinal permeability marker in autistic subjects. J Pediatr. 188:240–244. 2017.PubMed/NCBI View Article : Google Scholar
15	Tiffon C: The impact of nutrition and environmental epigenetics on human health and disease. Int J Mol Sci. 19(3425)2018.PubMed/NCBI View Article : Google Scholar
16	Rowland I, Gibson G, Heinken A, Scott K, Swann J, Thiele I and Tuohy K: Gut microbiota functions: Metabolism of nutrients and other food components. Eur J Nutr. 57:1–24. 2018.PubMed/NCBI View Article : Google Scholar
17	Petersen C and Round JL: Defining dysbiosis and its influence on host immunity and disease. Cell Microbiol. 16:1024–1033. 2014.PubMed/NCBI View Article : Google Scholar
18	De Angelis M, Piccolo M, Vannini L, Siragusa S, De Giacomo A, Serrazzanetti DI, Cristofori F, Guerzoni ME, Gobbetti M and Francavilla R: Fecal microbiota and metabolome of children with autism and pervasive developmental disorder not otherwise specified. PLoS One. 8(e76993)2013.PubMed/NCBI View Article : Google Scholar
19	Xu M, Xu X, Li J and Li F: Association between gut microbiota and autism spectrum disorder: A systematic review and meta-analysis. Front Psychiatry. 10(473)2019.PubMed/NCBI View Article : Google Scholar
20	Li Q, Han Y, Dy ABC and Hagerman RJ: The gut microbiota and autism spectrum disorders. Front Cell Neurosci. 11(120)2017.PubMed/NCBI View Article : Google Scholar
21	Song Y, Liu C and Finegold SM: Real-time PCR quantitation of clostridia in feces of autistic children. Appl Environ Microbiol. 70:6459–6465. 2004.PubMed/NCBI View Article : Google Scholar
22	Parracho HM, Bingham MO, Gibson GR and McCartney AL: Differences between the gut microflora of children with autistic spectrum disorders and that of healthy children. J Med Microbiol. 54:987–991. 2005.PubMed/NCBI View Article : Google Scholar
23	Finegold SM, Summanen PH, Downes J, Corbett K and Komoriya T: Detection of Clostridium perfringens toxin genes in the gut microbiota of autistic children. Anaerobe. 45:133–137. 2017.PubMed/NCBI View Article : Google Scholar
24	Sandler RH, Finegold SM, Bolte ER, Buchanan CP, Maxwell AP, Väisänen ML, Nelson MN and Wexler HM: Short-term benefit from oral vancomycin treatment of regressive-onset autism. J Child Neurol. 15:429–435. 2000.PubMed/NCBI View Article : Google Scholar
25	Vinithakumari AA, Padhi P, Hernandez B, Lin SJH, Dunkerson-Kurzhumov A, Showman L, Breitzman MW, Stokes C, Sulaiman Y, Tangudu CS, et al: Clostridioides difficile infection increases circulating p-cresol levels and dysregulates brain dopamine metabolism: linking gut-brain axis to autism spectrum disorders? bioRxiv, 2021.
26	Huang H, Weintraub A, Fang H and Nord CE: Antimicrobial resistance in Clostridium difficile. Int J Antimicrob Agents. 34:516–522. 2009.PubMed/NCBI View Article : Google Scholar
27	Kuhn M, Grave S, Bransfield R and Harris S: Long term antibiotic therapy may be an effective treatment for children co-morbid with Lyme disease and autism spectrum disorder. Med Hypotheses. 78:606–615. 2012.PubMed/NCBI View Article : Google Scholar
28	Busch C and Aktories K: Microbial toxins and the glycosylation of rho family GTPases. Curr Opin Struct Biol. 10:528–535. 2000.PubMed/NCBI View Article : Google Scholar
29	Netgazeti Healthcare. Management of autism spectrum disorder in Georgia: Khachapuridze E. http://netgazeti.ge/life/13498/. Accessed March 6, 2022.
30	Tevzadze G, Shanshiashvilli L and Mikeladze D: Children with epilepsy and autistic spectrum disorders show similarly high levels of urinary p-cresol. J Biol Phys Chem. 17:77–80. 2017.
31	Bauer AW, Kirby WM, Sherris JC and Turck M: Antibiotic susceptibility testing by a standardized single disk method. Am J Clin Pathol. 45:493–496. 1966.PubMed/NCBI
32	Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing, 29th edition. https://clsi.org/standards/products/microbiology/documents/m100/. Accessed March 6, 2022.
33	Makalatia K, Kakabadze E, Wagemans J, Grdzelishvili N, Bakuradze N, Natroshvili G, Macharashvili N, Sedrakyan A, Arakelova K, Ktsoyan Z, et al: Characterization of Salmonella isolates from various geographical regions of the caucasus and their susceptibility to bacteriophages. Viruses. 12(1418)2020.PubMed/NCBI View Article : Google Scholar
34	Mueller NT, Bakacs E, Combellick J, Grigoryan Z and Dominguez-Bello MG: The infant microbiome development: Mom matters. Trends Mol Med. 21:109–117. 2015.PubMed/NCBI View Article : Google Scholar
35	Yang I, Corwin EJ, Brennan PA, Jordan S, Murphy JR and Dunlop A: The infant microbiome: Implications for infant health and neurocognitive development. Nurs Res. 65:76–88. 2016.PubMed/NCBI View Article : Google Scholar
36	Zhang T, Sidorchuk A, Sevilla-Cermeño L, Vilaplana-Pérez A, Chang Z, Larsson H, Mataix-Cols D and Fernández-de-la-Cruz L: Association of cesarean delivery with risk of neurodevelopmental and psychiatric disorders in the offspring: A systematic review and meta-analysis. JAMA Netw Open. 2(e1910236)2019.PubMed/NCBI View Article : Google Scholar
37	Huang S, Wang X, Sun T, Yu H, Liao Y, Cao M, Cai L, Li X, Lin L, Su X and Jing J: Association of breastfeeding for the first six months of life and autism spectrum disorders: A national multi-center study in China. Nutrients. 14(45)2021.PubMed/NCBI View Article : Google Scholar
38	Khalil M, Azouz HG, Ahmed SA, Gad HA and Omar OM: Sensory processing and gastrointestinal manifestations in autism spectrum disorders: No relation to Clostridium difficile. J Mol Neurosci. 71:153–161. 2021.PubMed/NCBI View Article : Google Scholar
39	Ramirez PL, Barnhill K, Gutierrez A, Schutte C and Hewitson L: Improvements in behavioral symptoms following antibiotic therapy in a 14-year-old male with autism. Case Rep Psychiatry. 2013(239034)2013.PubMed/NCBI View Article : Google Scholar