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Gut Microbes and the Brain: What is the Effect on Human Behavior?

By Teresa L. Johnson, MSPH, RD

W. Allan Walker, MD, and Emeran Mayer, MD chaired a symposium during ASN’s Scientific Sessions and Annual Meeting on March 30 that considered the role the gut microbiome plays in human behavior.

Mark Lyte, PhD, MS, a professor at Texas Tech University, provided insights into aspects of gut-brain communication pathways. He introduced the idea that gut bacteria, as neuroendocrine organisms, are more interactive with their human hosts than previously believed. Lyte then pointed out that the gut is highly innervated, and information flows in a bi-directional but asymmetrical fashion between the gut and the brain, with as much as 90 percent of the information flowing from the gut. He suggested that neuroendocrine chemicals naturally present in foods might influence gut bacteria responses, and mechanisms that were previously considered immunological might be neuroendocrinal instead. The take-home message, Lyte said, was that these food-derived neurochemicals, when absorbed in gut, likely interact with the microbiota. In response, the microbiota produce neurochemicals that affect behavior and cognition in a sort of feedback loop. He cautioned that much of the data are correlational, and causation cannot be assigned.

Sarkis Mazmanian, PhD, California Institute of Technology, focused his remarks on specific molecular communications between the gut and brain. He explained that our bodies are in contact with trillions of microbes. “This microbial fingerprint has effects on many aspects of our biology,” said Mazmanian. He noted that in recent decades, the prevalence of autism spectrum disorder (ASD) has increased dramatically, and he presented data demonstrating that in rodents, maternal immune activation during pregnancy yields offspring with ASD and dysbiosis, suggesting a possible gut-microbiome-brain connection in ASD.

Premysl Bercik, MD, a gastroenterologist and associate professor at McMaster University, noted that while individuals with inflammatory bowel disorders commonly have abnormal gut function and low-grade inflammation, they also experience psychiatric comorbidities such as depression, stress, and anxiety. The trigger for this chain of events has not been identified, Bercik said, but some have hypothesized that infections or abnormal gut flora might be responsible. He then presented data from animal models that demonstrate the bi-directional communication between the gut and brain, and described recent research indicating that both microbial and host factors influence behavior.

Mayer, a professor at the David Geffen School of Medicine at UCLA, began his presentation with a historical perspective on the perceived gut-brain connection, which dates back several millennia. He then described notable limitations to using rodent models to study the gut-brain connection due to structural differences between rodent and human brains, and added that the germ-free mouse, a common model for understanding gut microbiome function, introduces many confounders into the research due to its altered metabolism. Mayer presented data that indicate that pre- and post-natal stress alters the gut microbiome in animals, as evidenced by both behavioral and biological changes, and he raised the idea that the gut microbial organization might influence brain structure. Attempts to modulate behavior with probiotics are promising, Mayer said, because intake blunts the reactivity of several internal organs, including those in the gut. Mayer concluded his presentation by cautioning that although enthusiasm to extrapolate findings from rodent models to human conditions including obesity, autism, and others is high, many questions remain about the role the gut microbiome plays in human health.