In recent years, a growing body of evidence has suggested a close relationship between the gut-brain axis and behavior. In one of the most recently published review papers on the subject, experts in the field highlighted studies that implicated the gut-brain axis in modulating emotional responses, pain, social interactions, and eating behaviors. Scientists have also suggested that dysfunction in the gut-brain axis contributes to symptoms of autism spectrum disorder (ASD), depression, and even chronic stress. While researchers are still working to provide strong clinical evidence connecting the composition of the gut microbiome to the structure and function of the brain in humans, there has been ongoing progress in vivo and in studies with animal models, which are motivating scientists to conduct clinical trials in the future.
One of the landmark papers that has kept researchers committed to the goal of understanding the relationship between the gut-brain axis and behavior was published in the high-powered journal Cell in 2013. This paper, which involved the use of mouse models, suggests that autism-associated behavioral abnormalities are modulated by gut physiology. The data also implies that dietary supplements like probiotics and short chain fatty acids may prove to be effective therapeutic options for patients with ASD or other conditions that are characterized by similar behavioral abnormalities.
Toward a Better Understanding of the Link between the Gut-Brain Axis and Behavior: A Study in Mouse Models
The 2013 Cell paper was the result of a collaboration between several research groups at California Institute of Technology and Baylor College of Medicine. The researchers premised their study on the observation that autism is characterized not only by behavioral abnormalities but also by gastrointestinal symptoms. Moreover, in the few years leading up to the study, there was growing evidence that many patients with autism had abnormalities related to their microbiota, which could contribute to symptoms related to both gastrointestinal motility and intestinal permeability. Even though the research community still has yet to identify any single characteristic microbiome “signature” that is common among all patients with autism, there appears to be a clear connection between the gut microbiome and GI symptoms of autism. The researchers who conducted this study decide to take it a step further by trying to find out whether the behavioral symptoms of autism might also be directly related to the gut microbiome.
To this end, they set up an experiment in which they created mouse models of autism and treated their symptoms with Bacterioides fragilis, a bacterial species in the colon that had previously been noted for its antibacterial properties potential contributions to anti-inflammatory processes. The first part of the research involved the development mouse models that displayed autism-like behaviors—including communicative abnormalities, anxiety-like behaviors, and sensorimotor problems—and they showed that these models also displayed abnormalities of the gut microbiome. This was consistent with the early recognition of the role of the gut-brain axis in patients with autism.
The next step was for the researchers to examine the effects of the B. fragilis probiotic supplement on the mouse models of autism. First, they showed that treatment with the supplement could restore increases in inflammation-associated proteins in the colon, mediating inflammatory bowel symptoms of autism. From there, they established that there was a clear, measurable change in the microbiota of the mouse models upon treatment with the probiotic supplement. And finally, they set out to test whether these physiological changes were associated with autism-related behavioral changes in the mouse models. Indeed, in the mouse models that took the probiotic B. fragilis supplement, the scientists observed improvements on the following tests:
- An open field exploration test that maps a mouse’s movement to assess its locomotor abilities and anxiety levels
- A marble-burying test that is used to determine a mouse’s anxiety levels in a natural situation
- An ultrasonic vocalization test that examines a mouse’s communication in social situations
Based on these findings, the authors were able to demonstrate that their mouse models demonstrated behavioral features of autism—and that oral supplementation with a probiotic B. fragilis supplement could reduce or even reverse these behaviors.
The Results of the Study in the Real-World Context
There’s no denying that a study in mouse models can never be a true substitute for rigorous clinical research, but this paper still provides strong support for a clear conclusion: that the microbiome modulates both gut physiology and the behavioral symptoms of autism. The evidence also indicates that probiotic supplements, especially those containing B. fragilis, may be able to ameliorate the behavioral symptoms of autism alongside the gastrointestinal problems.
When the findings are considered in the broader context of the research literature, they may also support the proposal that supplementation with short chain fatty acids can help address the behavioral symptoms of autism. Short chain fatty acids are multifunctional compounds that are produced when certain types of bacteria in the gut—including B. fragilis—ferment fiber that humans cannot digest. As more studies have connected short chain fatty acids with both the behavioral and gastrointestinal symptoms of autism, they are increasingly viewed as important regulators of the integrated gastrointestinal and neurological processes that comprise the gut-brain axis. Based on the findings of this study, higher levels of short chain fatty acids—whether provided through a gut-modulating probiotic supplement or directly introduced with an SFCA supplement—could potentially make a significant difference for practitioners and patients looking to address the behavioral symptoms of autism.
Next Steps for Research on the Gut-Brain Axis and Behavior
It’s been five years since the Cell paper was published, but the research on the gut-brain axis and behavior is still ongoing. Treatments ranging from elimination diets to fecal microbial transfer have been proposed, but rigorous clinical trials are still needed to compare the effectiveness of the options and consider how they might affect individual patients with diverse symptoms. As clinical trials get underway in the future, patients and practitioners may want to consider some of the possibilities that can provide results now, including specialized dietary supplements that can potentially address behavioral health outcomes for people living with ASD.
Den Besten G, van Eunen K, Groen AK, Vanema K, Reijngoud DJ, Bakker BM. 2013. The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism. Journal of Lipid Research. 54(9):2325-2340. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3735932/
Finegold SM, Molitoris D, Song Y, Liu C, Vaisanen ML et al. 2002. Gastrointestinal microflora studies in late-onset autism. Clinical Infectious Diseases. 35(Suppl 1): S6-S16. https://www.ncbi.nlm.nih.gov/pubmed/12173102
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. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3897394/
MacFabe DF. Short-chain fatty acid fermentation products of the gut microbiome: Implications in autism spectrum disorders. Microbial Ecology in health and Disease. 23. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3747729/
Macy JM, Ljungdahl LG, Gottschalk G. 1978. Path of succinate and propionate formation in Bacterioides fragilis. Journal of Bacteriology. 134(1):84-91. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC222221/
Martin CR, Mayer EA. 2017. Gut-brain axis and behavior. Nestle Nutrition Institute Workshop Series. 88:45-53. https://www.ncbi.nlm.nih.gov/pubmed/28346923
Vindigni SM, Zisman TL, Suskind DL, Damman CJ. 2016. The intestinal microbiome, barrier function, and immune system in inflammatory bowel disease: A tripartite pathophysiological circuit with implications for new therapeutic directions. Therapeutic Advances in Gastroenterology. 9(4):606-25. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4913337/
Wexler HM. 2007. Bacteroides: the good, the bad, and the nitty-gritty. Clinical Microbiology Reviews. 20(4):593-621. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2176045/