How Autism is Linked to Gut Bacteria and What it Means for the Future of Autism Treatment

In recent years, evidence has emerged supporting that notion that autism spectrum disorder (ASD) may be linked to gut bacteria. Clarification of these connections is now helping scientists, clinicians, parents, and patients better understand the complexities of autism-related symptoms and their potential causes. A growing body of scientific literature is also paving the way for the development of potential preventive therapies and treatment options that specifically target the gut microbiome in order to provide symptom relief.

Understanding How Autism is Linked to Gut Bacteria in Patients

Scientists first suspected that autism may be linked to gut bacteria based on the fact that GI symptoms like constipation and diarrhea are commonly experienced by individuals with autism. According to one estimate, for example, children with autism are about 19 percent more likely to have GI syndromes than their siblings without autism. It was clear that scientists were on the right track when studies began showing that there were significant differences between populations of gut bacteria in patients with autism and healthy controls. One study from 2013 indicates that levels of Bifidobacterium species are lower in children with autism than in healthy controls, while levels of bacteria from the Caloramator, Sarcina, and Clostridium genera tend to be higher. Similarly, a 2015 study found lower levels of bacteria in the Prevotella and Coprococcus genera, as well as the unclassified Veillonellaceae bacterial group, in patients with autism. This study is particularly interesting, as it was conducted in patients with autism who had minimal GI symptoms. Through their findings, the authors were able to establish an association between the abundance of the gut bacteria and the presence of autism-related symptoms rather than the severity of gastrointestinal symptoms, indicating that disturbances in gut bacteria populations may elicit neurobehavioral symptoms via the gut-brain connection.

In addition to differences in abundance of particular types of gut bacteria, multiple studies have also found less diversity in the gut microbiota of patients with autism than in healthy controls, both within and between bacterial phyla. Based on these data, some researchers have hypothesized that symptoms of autism may be linked to lower levels of beneficial chemicals that are produced when bacteria break down molecules in the gut. For instance, one study found that 4-ethylphenylsulfate, a metabolite produced by Bacteroides fragilis, could help reduce autism-like symptom in mouse models. Additionally, Prevotella, Coprococcus, and Veillonellaceae can all produce an unusually broad spectrum of metabolites, from which patients with autism are less likely to benefit due to their reduced abundance.

It is important to note that it is not yet entirely clear whether differences in microbial diversity have a causal or consequential association relationship with autism. However, one study in mice supports the hypothesis that changes in the gut microbiome may be causally linked to some autism symptoms. In a mouse model of autism characterized by anxiety and abnormal communication behaviors, researchers found that the mouse models are born with gut microbiota that differ in composition from those of healthy controls. Significantly, they also found that some of their anxiety and communication-related behaviors can be lessened with the introduction of a certain species of bacteria. This supports the theory that manipulation of the gut microbiome may provide new treatment possibilities for patients with autism.

However, reduced microbial diversity may not be the only link between gut bacteria in autism. A 2017 review paper highlights a combination of evidence from in vitro experiments, animal studies, and human studies indicating that symptoms of autism are associated with higher levels of intestinal permeability and defects in the gastrointestinal barrier. Put more simply, this means that, in patients with autism, metabolites are more likely to “leak” out of the gut into the bloodstream. As a result, toxins and bacterial products produced by bacteria like Lactobacillus may end up reaching the brain, where they can disrupt chemical balances and possibly exacerbate symptoms.

How a Mother’s Gut Bacteria Can Affect A Child’s Risk of Autism

Alongside the large body of research linking the gut microbiota of patients with autism to their symptoms, several exciting new studies have shed light on how autism may be linked to the gut bacteria of the mother. For instance, in an August 2017 study, researchers at the University of Illinois examined whether the composition of the microbiota of female pigs could affect the neurodevelopment of piglets. They noticed several significant relationships between the gut bacteria of mother pigs and the brain chemistry of their offspring, including a number of chemical irregularities previously observed in patients with autism. Specifically, they found that higher levels of the genera Bacteroides and Clostridium in mother pigs were associated with higher concentrations of the brain chemical myo-inositol in piglets. Elevated abundance of Bacteroides was also associated with higher levels of creatine in the brain. Higher levels of Butyricimonas were associated with higher concentrations of the chemical n-acetylaspartate (NAA), while higher levels of Ruminococcus were associated with lower levels of NAA in the brain. This study paves the way for future research on how a mother’s gut microbiome may affect neurodevelopment, and, in particular, the development of autism.

Recent epidemiological studies have also provided strong evidence demonstrating that women who experience a severe infection during pregnancy have a significantly higher risk of having a child with autism. In September 2017, researchers from MIT published a groundbreaking study that indicated, in mouse models, that the composition of the mother’s gut microbiome at the time of the infection can affect the risk that the infection will lead to ASD symptoms in the offspring. Certain strains of gut bacteria promote the development of certain types of immune cells and others are involved in activating those immune cells. The authors demonstrated that the activities of these bacteria were directly related to abnormalities caused by maternal immune activation.

Future Research Options for Treating Autism Linked to Gut Bacteria

There is now solid evidence that autism is linked to gut bacteria, in both mothers and in the patients themselves. However, researchers remain hesitant about advocating specific prevention or treatment strategies, since large-scale studies have yet to be conducted. Preliminary research and anecdotal evidence indicate that probiotics, prebiotics, and dietary changes may all be effective for reducing symptoms in patients with autism. For instance, in a 2016 case study of a 12-year-old boy with an ASD diagnosis, a four-week treatment with a probiotic containing ten different strains led to significant improvements in social affect (a category that broadly includes multiple symptoms of autism) and chronic constipation. Based on results like these, clinicians, patients, and parents are looking forward to larger studies that can confirm initial findings. Researchers have also proposed more targeted treatments to manipulate the gut microbiome in patients with autism, such as fecal transplants, but these will also require more rigorous trials.

Additionally, the MIT researchers who studied how viral infections can affect autism risk have proposed treating mothers with therapeutics that block the activity of certain strains of gut bacteria. However, this remains a long way off, since their initial findings in mice must first be validated in humans before drug development can become feasible.

Overall, it is clear that there are strong links between autism and gut bacteria. It will be exciting to follow future studies probing autism linked to gut bacteria, especially as researchers seek to develop therapeutics that can make a difference in the lives of patients and parents.

Foundational Medicine Review provides reliable, evidence-based information about gastrointestinal health, neurological disorders, and the links between them. Join our mailing list to stay up-to-date on the latest news, research, and analysis.

Works Cited

DeAngelis M, Piccolo M, Vannini L, Siragusa S, De Giacomo A et al. 2013. Fecal microbiota and metabolome of children with autism and pervasive developmental disorder not otherwise specified. PLOS One.

Grossi E., Melli S, Dunca D, Terruzzi V. 2016. Unexpected improvement in core autism spectrum disorder symptoms after long-term treatment with probiotics. SAGE Open Medical Case Reports, 4.

Hsiao EY, McBride SW, Hsien S, Sharon G, Hyde ER et al. 2013. The microbiota modulates gut physiology and behavioral abnormalities associated with autism. Cell. 155(7):1451-63.

Kim S, Kim H, Yim YS, Ha S, Atarashi K et al. 2013. Maternal gut bacteria promote neurodevelopmental abnormalities in mouse offspring. Nature. 549:528-32.

Krajmalnik-Brown R., Lozupone C, Kang DW, Adams JB. 2015. Gut bacteria in children with autism spectrum disorders: Challenges and promise of studying how a complex community influences a complex disease. Microbial Ecology in Health and Disease. 26.

Li Q, Han Y, Dy ABC, Hagerman RJ. 2017. The gut microbiota and autism spectrum disorders. Frontiers in Cellular Neuroscience.

Mudd AT, Berding K, Wang M, Donovan, S, Dilger RN. 2017. Serum cortisol mediates the relationship between fecal Ruminococcus and brain N-acetylaspartate in the young pig. Gut Microbes. 8(6):589-600.

Wang LW, Tancredi DJ, Thomas DW. 2011. The prevalence of gastrointestinal problems in children across the United States with autism spectrum disorders from families with multiple affected members. Journal of Developmental and Behavioral Pediatrics. 32(5):351-60.

Zergo O, Qian Y, Yoshida C, Grether JK, deWater J et al. 2015. Maternal infection during pregnancy and autism spectrum disorders. Journal of Autism and Developmental Disorders. 45(12):4015-25.

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