The Gut-Microbiome and Autism: A Scientific Dive into how the Gut Microbiome is delicately intertwined in Autism Spectrum Disorder (ASD)

Emerging research reveals a profound link between the gut microbiome and autism spectrum disorder (ASD), reshaping our understanding of how digestive health influences brain development and behavior. While causality remains unproven, mounting evidence highlights microbial imbalances, metabolic disruptions, and immune interactions as key players in ASD disease process.

Gut Dysbiosis in Autism

Children with ASD often exhibit uniquely different gut microbial profiles compared to neurotypical individuals. Studies have reported elevated levels of Clostridia species and reduced populations of Bifidobacterium and Prevotella. These shifts correlate with gastrointestinal symptoms like constipation or diarrhea, which affect up to 70% of individuals with Autism. Notably, Clostridia produce propionic acid; this metabolite has been linked to mitochondrial dysfunction and repetitive behaviors in animal models. Key microbial differences include overgrowth of Desulfovibrio and Sutterella, associated with intestinal inflammation. Reduced microbial diversity has become a marker for measuring ASD severity. This is because ~ 90% of serotonin and more than 50% of dopamine are synthesized by gut bacteria. This disruption in neurotransmitter production leads to more of the neurological symptoms of ASD.  

How these two worlds intertwine-The Gut-Brain Axis

Gut microbes produce metabolites that cross the blood-brain barrier, influencing neural activity. Short-Chain Fatty Acids (SCFAs) are the first example of these metabolites produced by bacteria and are the primary energy source for the colon and the cells that comprise the lining, known as colonocytes. These metabolites can become dysregulated by the disproportionate abundance of certain genera of bacteria. Excess propionic acid (a SCFA precursor) from Clostridia may impair energy production in brain cells and exacerbate social deficits. Butyrate (another SCFA), typically anti-inflammatory, is often depleted in ASD gut microbiomes. Further, Autistic children show altered tryptophan processing (a process by gut bacteria), reducing protective metabolites like kynurenate.  This disrupts emotional and sensory processing networks in the brain. Lastly, immune and barrier dysfunction, seen as "leaky gut", present commonly in ASD. Leaky gut allows bacterial toxins like lipopolysaccharide (LPS) to enter circulation, triggering neuroinflammation. This is compounded by elevated amounts of proteins that signal cells (proinflammatory cytokines) and coordinate immune responses that have been correlated with social impairment.

Talukdar MA, Molla AA, Akter S, Uddin NE, Islam MM, Hasan ST, Ahmed MA, Parvez BR, Xu J, Choi HJ. Role of Gut Microbiome in Autism Spectrum Disorder and Its Therapeutic Regulation. Front Cell Infect Microbiol. 2022;12:915701

Therapeutic Horizons

Targeting the gut microbiome offers promising avenues.  Probiotics (e.g., L. reuteri) restore microbial balance and reduce inflammation. In rodent models, this has been shown to improve behavior. Dietary Modifications via increasing fiber and other prebiotics to boost neuroprotective SCFA production have been shown to mitigate gastrointestinal distress and behavioral symptoms. If you suspect you or anyone in your life has a microbial imbalance, and you have questions about how this can be further investigated, please schedule a free consultation with me, Melody Bartlett, at Brain and Body Rehabilitation at 404-671-8499. In partnership with Microbiome Labs, we have the resources to bridge the gap between what we know in science and how to use it, starting today.

Conclusion

The gut microbiome emerges as a dynamic interface between the environment and the brain in autism. While not a sole culprit, its modulation through diet and probiotics could complement behavioral therapies. As research deciphers specific microbial strains and metabolic pathways involved, we move closer to precision treatments that address both gut and brain health in ASD.

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