How Gut Modulation Could Improve Autism Symptoms
Autism spectrum disorder is a term used to describe people with impaired communication, difficulties with social interaction, and obsessive & repetitive behaviors; these symptoms can range in severity, thus autism existing on a “spectrum”. It can be difficult to clinically diagnose due to a lack of quantitative medical tests, and its has greatly increased in global prevalence in recent years.² This could be due to increased awareness and screening, but other researchers hypothesize it could be related to changes in gut microbiome composition and the loss of microbial diversity that mirror the industrialization and over-sanitization of society. Altered gut microbiome compositions and increased epithelial permeability are strongly associated with autism development.³
Ellen Bolte could be considered the pioneer of relating antibiotic use (and thus modulation of the gut microbiome) and autism. Her son developed autism after several rounds of antibiotic treatment, and she hypothesized that the destruction of his microbiome left room for pathogenic species to grow uninhibited in his GI tract, increasing inflammation, altering epithelial permeability, and producing microbial metabolites and toxins that induced autism symptoms. One such toxin that has been studied extensively in mice is 4EPS, a microbial metabolite that can travel to the brain and induce anxiety-like behavior.⁴
However, administration of Bacteroides fragilis reverses this anxiety-like behavior in mice.⁵ By targeting tight junction and cytokine expression, B. fragilis can correct gut permeability and improve intestinal health, perhaps preventing 4EPS leakage.⁵ Interestingly enough, the gut microbiomes of those with autism are known to lack B. fragilis.
It is hard to ignore the potential of microbiome modulation and probiotic therapy in treating autism, as well as other neurological conditions. Given the increasing awareness of the intricacies of the gut-brain axis, it makes sense that we are learning how microbial communities and epithelial integrity affect behavior. It calls into question just how much the trillions of microbes in our guts affect our personalities and phenotypes. The gut-brain axis is a fascinating bidirectional pathway that warrants more research and ignites hope of exciting possibilities in the future of medicine.
References
Yong E. I contain multitudes: The microbes within us and a grander view of life. London, England: Vintage; 2017.
Zeidan J, Fombonne E, Scorah J, Ibrahim A, Durkin MS, Saxena S, et al. Global prevalence of autism: A systematic review update. Autism Res [Internet]. 2022;15(5):778–90. Available from: http://dx.doi.org/10.1002/aur.2696
Fattorusso A, Di Genova L, Dell’Isola G, Mencaroni E, Esposito S. Autism spectrum disorders and the gut Microbiota. Nutrients [Internet]. 2019 [cited 2023 Aug 29];11(3):521. Available from: http://dx.doi.org/10.3390/nu11030521
Stewart Campbell A, Needham BD, Meyer CR, Tan J, Conrad M, Preston GM, et al. Safety and target engagement of an oral small-molecule sequestrant in adolescents with autism spectrum disorder: an open-label phase 1b/2a trial. Nat Med [Internet]. 2022 [cited 2023 Aug 29];28(3):528–34. Available from: https://www.nature.com/articles/s41591-022-01683-9
Hsiao EY, McBride SW, Hsien S, Sharon G, Hyde ER, McCue T, et al. Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell [Internet]. 2013 [cited 2023 Aug 29];155(7):1451–63. Available from: http://dx.doi.org/10.1016/j.cell.2013.11.024