Updated on February 2, 2023
- Growing awareness of the reciprocal relationship between the brain and the gut is spurring researchers to investigate potential new therapies for autism spectrum disorder that focus on manipulating the gut microbiome.
- Evidence suggests that a number of nutritional supplements can address both gastrointestinal and behavioral symptoms of autism by acting on the gut-brain axis.
- Butyric acid supplements might be particularly promising for those seeking to explore this new paradigm of autism therapy.
In recent years, a growing body of evidence suggests a close relationship between the gut-brain axis and behavior. In a 2017 review on the subject, experts in the field highlighted studies that implicate 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 stress. Although researchers are still working to provide strong clinical evidence that connects the composition of the gut microbiome to the structure and function of the brain, there has been ongoing progress in vivo and in studies with animal models, which are motivating scientists to conduct clinical trials.
One of the landmark papers keeping 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 utilizing 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, such as butyric acid, could offer effective therapeutic options for patients with ASD or other conditions 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 preceding the study, there was growing evidence that many autism patients 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 not identified a single characteristic microbiome “signature” that is common among all autism patients, there appears to be a clear connection between the gut microbiome and the GI symptoms of autism. The researchers who conducted this study took it a step further by determining whether the behavioral symptoms of autism might also be directly related to the gut microbiome.
They set up an experiment in which they created mouse models of autism and treated these symptoms with Bacterioides fragilis, a bacterial species found in the colon noted for its antibacterial properties and potential contributions to the body’s natural inflammatory response. The first part of the research involved the development of mouse models that display autism-like behaviors—including communicative abnormalities, anxiety-like behaviors, and sensorimotor problems—and they showed that these models also display 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 a B. fragilis probiotic supplement on the mouse models of autism. First, they showed that therapy with the supplement could restore increases in inflammation-associated proteins in the colon, thus mediating inflammatory bowel symptoms of autism. From there, they established there is a clear, measurable change in the microbiota of the mouse models after therapy with the probiotic supplement. And finally, they set out to test whether these physiological changes are 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 positive outcomes on the following tests:
- An open field exploration test that maps a mouse’s movement by assessing its locomotor abilities and anxiety levels
- A marble-burying test 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 demonstrated that their mouse models showed the behavioral features of autism—and that oral supplementation with a probiotic B. fragilis supplement could diminish or even reverse these behaviors.
The Results of the Study in the Real-World Context
Certainly, a study in mouse models cannot be a true substitute for rigorous clinical research, although this paper does provide strong support for the conclusion that the microbiome does modulate both gut physiology and the behavioral symptoms of autism. The evidence also indicates that probiotic supplements, especially those containing B. fragilis, might be able to ameliorate the behavioral symptoms of autism in addition to the gastrointestinal problems.
When these findings are considered in the broader context of the research literature, they might 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, particularly butyric acid, with both the behavioral and gastrointestinal symptoms of autism, short-chain fatty acids are increasingly being viewed as important regulators of the integrated gastrointestinal and neurological processes that comprise the gut-brain axis. Based on these findings, it is reasonable to conclude that higher levels of short-chain fatty acids—whether provided through a gut-modulating probiotic supplement or directly introduced with a short-chain fatty acid 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
Although it’s been five years since the Cell paper was published, research on the gut-brain axis and behavior is ongoing. Therapies ranging from elimination diets to fecal microbial transfer have been proposed, and rigorous clinical trials are still needed to compare the effectiveness of the options and to determine how they might affect individual patients with diverse symptoms. As future clinical trials get underway, patients and practitioners might want to consider some of the possibilities that can provide results now, including specialized dietary supplements, that can potentially address behavioral health outcomes for individuals with ASD.
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Works Cited
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