We’ve all seen some form of representation of Autism Spectrum Disorder (ASD), be it on social media, in a TV show, or observing it in our family members. Intriguingly, a series of research studies have shown an unlikely yet intricate connection between ASD and the gut microbiome.

ASD refers to a group of neurodevelopmental conditions of variable severity having features regarded as characteristic of autism (especially difficulties with social interaction and communication). The gut microbiome refers to the system of microorganisms that live in the digestive tract of humans and other animals.

Before being born, one’s gut microbiome may be influenced by factors such as antibiotic use, mode of birth (cesarean section vs. vaginal birth), or maternal health during pregnancy.

Neurological issues

The gut microbiome plays an undeniably pivotal role in the immune system, reducing inflammation, defending against bacteria, and protecting against chronic autoimmune diseases such as rheumatoid arthritis and inflammatory bowel disease (IBS). But the gut microbiome is incredibly delicate. The ecosystem of bacteria within the gut is extremely sensitive to changes in one’s diet, medication and environment. Unpredicted changes to the gut microbiome might increase the frequency and intensity of neurological issues that are commonly observed in people with ASD, such as difficulty in processing sensory information or regulating one’s emotions.

Mood control

The gut microbiome is also involved in the production of neurotransmitters, which are chemicals that affect your mood and behaviour such as serotonin. In fact, studies have shown that 90% of the serotonin in our brain is synthesised by cells in our gastrointestinal tract! It has been established that children with ASD often display an excess of serotonin, which has been postulated as the result of a hyper-secretion of 5-HT, one of the components of serotonin.

Apart from neurotransmitters, gut bacteria also produce metabolites, such as short-chain fatty acids and amino acids. Since these cannot cross the blood-brain barrier, they act on the enteric nervous system (a system of neurons within the walls of the gastrointestinal tract), indirectly influencing one’s behavior and cognitive abilities. For example, reduced short-chain fatty acid levels could lead to depressive episodes and heightened risk of oxidative stress. Research has shown that children with autism have different levels of metabolites in their urine or blood, which could be linked to differences in their gut microbiomes. Not only is this paramount in understanding how the diet of people with ASD may impact their mood and behaviour, it may also prove useful in diagnosing ASD early.

In order to mediate excessive or insufficient secretion of certain components, it is recommended that people with ASD engage in diets that promote gut health, such as low-glycemic, gluten-free, or casein-free diets.

The gut-brain axis connecting the brain to the intestinal tract.

Oxidative stress

Oxidative stress is an imbalance of free radicals in one’s body that leads to cell damage. This phenomenon is especially common in ASD, and may even be a cause of a majority of the symptoms of ASD.

Oxidative stress leads to protein post-translational changes, abnormal metabolism, and toxic buildup in the body, directly affecting the gut microbiome. This damages brain cells, interferes with neurotransmission and contributes to inflammation, exacerbating the symptoms of ASD.

Studies and Findings

Several studies have found evidence of gut microbiome differences in people with autism. One study published in Cell in 2013 found that children with autism had lower levels of certain gut bacteria (like Bifidobacterium and Prevotella) and higher levels of others compared to typical developing children. Other studies have found that people with autism often have gastrointestinal issues, like constipation or diarrhea, which could be linked to gut microbiome imbalances.

A 2017 study from Frontiers in Cellular Neuroscience explored how gut bacteria might influence the brain in autism. The researchers found that when they altered the gut microbiome in mice, it changed their behavior and social interactions, providing evidence that the gut microbiome might have a direct impact on brain function.

Scientists are still investigating the fascinating connection between the gut microbiome and autism spectrum disorder, to determine whether altering the microbiome in people with ASD could help ease the disruptive symptoms of autism. A study in 2019 showed that giving children with autism a specific probiotic improved their social behavior and reduced anxiety. This has encouraged more scientists to explore whether heightened consumption of probiotics, changes to one’s diet, or even fecal transplants (transferring stool from a healthy person to another person) might help balance the gut microbiome and improve the experiences of those with ASD.

Knowing the link between the gut microbiome and autism spectrum disorder is paramount in helping doctors diagnose and treat individuals with ASD. There are currently no clinical biomarkers for ASD, since the disorder is complex, and its pathogenesis is unknown. However, with information about the individual’s gut microbiome, we can diagnose ASD based on an autism-specific history and clinical observation. Hopefully, this is a step forward in efficiently diagnosing and improving the lives of people with autism.

References:

Alharthi, A., Alhazmi, S., Alburae, N., & Bahieldin, A. (2022). The Human Gut Microbiome as a Potential Factor in Autism Spectrum Disorder. International Journal of Molecular Sciences, 23(3), 1363. https://doi.org/10.3390/ijms23031363
Carabotti, M., Scirocco, A., Maselli, M. A., & Severi, C. (2015). The gut-brain axis: interactions between enteric microbiota, central and enteric nervous systems. Annals of gastroenterology, 28(2), 203–209.
Zheng, D., Liwinski, T. & Elinav, E. Interaction between microbiota and immunity in health and disease. Cell Res 30, 492–506 (2020). https://doi.org/10.1038/s41422-020-0332-7
Likhitweerawong, N., Thonusin, C., Boonchooduang, N., Louthrenoo, O., Nookaew, I., Chattipakorn, N., & Chattipakorn, S. C. (2021). Profiles of urine and blood metabolomics in autism spectrum disorders. Metabolic brain disease, 36(7), 1641–1671. https://doi.org/10.1007/s11011-021-00788-3
Liu X, Lin J, Zhang H, Khan NU, Zhang J, Tang X, Cao X, Shen L. Oxidative Stress in Autism Spectrum Disorder-Current Progress of Mechanisms and Biomarkers.
Fattorusso, A., Di Genova, L., Dell'Isola, G. B., Mencaroni, E., & Esposito, S. (2019). Autism Spectrum Disorders and the Gut Microbiota. Nutrients, 11(3), 521. https://doi.org/10.3390/nu11030521
Does Seratonin in the intestines make you happy? (n.d.). National Library of Medicine. https://pmc.ncbi.nlm.nih.gov/articles/PMC7659911/
Kim C. S. (2024). Roles of Diet-Associated Gut Microbial Metabolites on Brain Health: Cell-to-Cell Interactions between Gut Bacteria and the Central Nervous System. Advances in nutrition (Bethesda, Md.), 15(1), 100136. https://doi.org/10.1016/j.advnut.2023.10.008
Cheng, J., Hu, H., Ju, Y., Liu, J., Wang, M., Liu, B., & Zhang, Y. (2024). Gut microbiota-derived short-chain fatty acids and depression: deep insight into biological mechanisms and potential applications. General psychiatry, 37(1), e101374. https://doi.org/10.1136/gpsych-2023-101374

Media:

https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2022.820106/full
https://medicalxpress.com/news/2022-12-microbiota-therapy-term-gut-health.html

Issue 4 - Apr 2025

Articles - Cell Biology and Biochemistry