Features of the gut microbiota composition and its metabolites in children with autism spectrum disorders

In recent years, the prevalence of autism spectrum disorders has increased among the population. This group of patients also has a high frequency of associated somatic diseases. By affecting a key pathogenetic mechanism—the “microbiota-gut-brain” axis—these conditions can influence the severity of the main symptoms of the disease, which requires the development of new methods for correcting somatic pathologies.

The aim of the study: to research the state of the intestinal microbiota and its metabolites in children with autism spectrum disorders to optimize approaches to correcting the main symptoms of the disease.

Materials and methods. The study involved 95 children with autism spectrum disorders (2–8 years old) and 26 children in the Control group (3–8 years old). Fecal samples were collected from patients with autism spectrum disorders before the intervention (ASD1) and 6 months after dietary correction and a course of probiotics (ASD2); from the Control group, a single sample was collected. Bacteriological analysis, determination of short-chain fatty acid and fecal calprotectin levels were performed. Gastrointestinal symptoms and neuropsychological development indicators were additionally assessed.

Results: Bacteriological examination of feces revealed significant differences in the ASD1 and ASD2 groups only in the level of Escherichia coli (lactose-positive) (p=0.021). Evaluation of intestinal metabolite levels revealed more significant differences, in particular, a significant increase in isocaproic acid (iC6) (p=0.008) in the ASD1 group compared to the Control, and its significant decrease against the background of the correction, which also directly correlated with the neuropsychic development indicators in the ASD1 and ASD2 groups (p=0.001).

Conclusion. Influencing the gut microbiota through dietary modification and probiotic use has demonstrated positive dynamics in intestinal metabolite levels, as well as parameters of neuropsychological development. A personalized dietary and microbiological approach provides the basis for developing comprehensive treatment options for children with autism spectrum disorders.

1. Hodges H., Fealko C., Soares N. Autism spectrum disorder: definition, epidemiology, causes, and clinical evaluation. Transl Pediatr. 2020;9(Suppl 1): S55-S65. DOI: 10.21037/tp.2019.11.04

2. Młynarska E., Barszcz E., Budny E., Gajewska A., Kopeć K., Wasiak J. et al. The Gut-Brain-Microbiota Connection and Its Role in Autism Spectrum Disorders. Nutrients 2025; 17: 1135. DOI: 10.3390/nu17071135

3. Silva Y.P., Bernardi A., Frozza R.L. The role of short-chain fatty acids from gut microbiota in gut-brain communication. Front Endocrinol (Lausanne) 2020; 11: 25. DOI: 10.3389/fendo.2020.00025

4. Liu S., Li E., Sun Z., Fu D., Duan G., Jiang M. et al. Altered gut microbiota and short chain fatty acids in Chinese children with autism spectrum disorder. Sci Rep 2019; 9(1): 287. DOI: 10.1038/s41598-018-36430-z

5. Tsao S., Zolnikova O.Yu., Maslennikov R.V., Poluektova E.A., Bueverova E.L., Reshetova M.S. et al. Metabolic profiles of the gut microbiota in patients with different stages of metabolic associated fatty liver disease. Rossiiskii zhurnal gastroenterologii, gepatologii, koloproktologii 2024; 34(4): 64–74. (in Russ.). DOI: 10.22416/1382-4376-2024-34-4-64-74

6. Krasakov I.V., Litvinenko I.V., Rodionov G.G., Davydova N.I., Aleksanin S.S., Svetkina E.V. The role of short-chain fatty acids in the pathogenesis of Parkinson’s disease. Izvestiia Rossiiskoi Voenno-meditsinskoi akademii 2022; 41(4): 439–444. (in Russ.). DOI: 10.17816/rmmar111854

7. Zahedi E., Sadr S.S., Sanaeierad A., Roghani M. Chronic acetyl-L-carnitine treatment alleviates behavioral deficits and neuroinflammation through enhancing microbiota derived-SCFA in valproate model of autism. Biomed Pharmacother 2023; 163: 114848. DOI: 10.1016/j.biopha.2023.114848

8. Chamtouri M., Gaddour N., Merghni A., Mastouri M., Arboleya S., de Los Reyes-Gavilán C.G. et al. Age and severity-dependent gut microbiota alterations in Tunisian children with autism spectrum disorder. Sci Rep 2023; 13(1): 18218. DOI: 10.1038/s41598-023-45306-w

9. Tkachuk E.A., Martynovich N.N., Globenko N.E. Features of nutritional status and nutrition in children with autism spectrum disorders. Voprosy pitaniia 2021; 90(5): 67– 76. (in Russ.) DOI: 10.33029/0042-8833-2021-90-5-67-76

10. Shaaban S.Y., El Gendy Y.G., Mehanna N.S., El-Senousy W.M., El-Feki H.S.A., Saad K. et al. The role of probiotics in children with autism spectrum disorder: A prospective, open-label study. Nutr Neurosci 2018; 21(9): 676–681. DOI: 10.1080/1028415X.2017.1347746

11. Kaczmarek A., Skowron K., Budzyńska A., Grudlewska K., Gospodarek-Komkowska E. Virulence genes and antimicrobial susceptibility of lactose-negative and lactose-positive strains of Escherichia coli isolated from pregnant women and neonates. Folia Microbiol (Praha) 2017; 62(5): 363–371. DOI: 10.1007/s12223-017-0505-z

12. Yang C., Xiao H., Zhu H., Du Y., Wang L. Revealing the gut microbiome mystery: A meta-analysis revealing differences between individuals with autism spectrum disorder and neurotypical children. Biosci Trends 2024; 18(3): 233–249. DOI: 10.5582/bst.2024.01123

13. Bezrodnyy S.L. Gut microbiota and autism spectrum disorder in children. Rossiyskiy Pediatricheskiy Zhurnal (Russian Pediatric Journal). 2019;22(1):51–56. (in Russ.) DOI: 10.18821/1560-9561-2019-22-1-51-56

14. Mayatskaya T.A., Kharitonova L.A., Papysheva O.V., Zatevalov A.M. Formation of the intestinal microbiocenosis in children born to mothers with gestational diabetes mellitus. Eksperimental’naya i klinicheskaya gastroenterologiya 2021; 185(1): 96–105. (in Russ.). DOI: 10.31146/1682-8658-ecg-185-1-96-105

15. Funk I.A., Irkitova A.N. Biotechnological potential of bifidobacteria. Acta Biologica Sibirica 2016; 2(4): 67–78. (in Russ.). DOI: 10.14258/abs.v2i4.1594

16. Blagonravova A.S., Zhilyaeva T.V., Kvashnina D.V. Gut microbiota disorders in autism spectrum disorders: new horizons in the search for pathogenetic approaches to therapy. Part 2. The gut-brain axis in the pathogenesis of autism spectrum disorders. Zhurnal Mikrobiologii, Epidemiologii i Immunobiologii. 2021;98(2):221–230. (in Russ.). DOI: 10.36233/0372-9311-83

17. Claassen-Weitz S., Shittu A.O., Ngwarai M.R., Thabane L., Nicol M.P., Kaba M. Fecal Carriage of Staphylococcus aureus in the Hospital and Community Setting: A Systematic Review. Front Microbiol 2016; 7: 449. DOI: 10.3389/fmicb.2016.00449

18. Macfabe D.F. Short-chain fatty acid fermentation products of the gut microbiome: implications in autism spectrum disorders. Microb Ecol Health Dis 2012; 23: 19260. DOI: 10.3402/mehd.v23i0.19260

19. Potap E.V., Kuskova T.M., Kutkina A.A., Suravitskaya O.E., Sivkova N.M., Mikhailova G.V. et al. The frequency of isolation of hemolytic Escherichia coli (E. coli Hly+) and its effect on bifidobacteria in tests for dysbiosis. Infektsiya i immunitet 2016; 6(3): 255– 260. (in Russ.). DOI: 10.15789/2220-7619-2016-3-255-260

20. Hadrich I., Turki M., Chaari I., Abdelmoula B., Gargouri R., Khemakhem N. et al. Gut mycobiome and neuropsychiatric disorders: insights and therapeutic potential. Front Cell Neurosci 2025; 18: 1495224. DOI: 10.3389/fncel.2024.1495224

21. Han R., Nusbaum O., Chen X., Zhu Y. Valeric acid suppresses liver cancer development by acting as a novel HDAC inhibitor. Mol Ther Oncolytics 2020; 19: 8–18. DOI: 10.1016/j.omto.2020.08.017

22. Ran-Ressler R.R., Glahn R.P., Bae S., Brenna J.T. Branched Chain Fatty Acids (BCFA) in the neonatal gut, and estimated dietary intake in infancy and adulthood. Nestle Nutr Inst Workshop Ser 2013; 77: 133–143. DOI: 10.1159/000351391

23. Markowiak-Kopeć P., Śliżewska K. The Effect of Probiotics on the Production of Short-Chain Fatty Acids by Human Intestinal Microbiome. Nutrients 2020; 12(4): 1107. DOI: 10.3390/nu12041107

24. Zou M., Zhang Y., Li D., Li S., Hu J., Gao Y. et al. Correlation of Co-Morbidities with Symptom Severity of Children with Autism Spectrum Disorder: A Cross-Sectional Survey. Nutrients 2024; 16(17): 2960. DOI: 10.3390/nu16172960

25. Karpeeva Yu.S., Novikova V.P., Khavkin A.I., Kovtun T.A., Makarkin D.V., Fedotova O.B. Microbiota and human diseases: possibilities of dietary correction. Rossiyskiy vestnik perinatologii i pediatrii 2020; 65(5): 116–125. (in Russ.). DOI: 10.21508/1027-4065-2020-65-5-116-125