MIAMI BEACH – The rich microbial diversity we all carry within our guts “talks” to our brains, and our brains talk back. The state of the very new field of “psychobiotics” was reviewed in a panel session at a meeting of the American Society of Clinical Psychopharmacology, formerly known as the New Clinical Drug Evaluation Unit meeting.
The National Institutes of Health’s National Center for Complementary and Integrative Health, formerly known as the National Center for Complementary and Alternative Medicine, or NCCAM, convened the workshop to bring together panelists from the bench to the bedside to discuss the state of research on the brain-gut-microbiome axis.
Daniel McDonald of the University of Colorado Boulder spoke about the American Gut Project. This crowd-funded project aggregates a very large number of gut microbiota samples and, using a standardized biosequencing protocol, compiles deidentified data for analysis. Using an ordination technique called principal coordinates analysis, researchers are able to use data processing and visualization techniques that show clustering of microbiota types and can show effect sizes for participant characteristics and lifestyles, such as alcohol use, basic diet type, age, and geographic location.
To date, 4,200 participants have had their gut microbiota sequenced. Several sub-projects focus on analysis with broad implications for neurologic and psychological research; these include a project focusing on the microbiomes of intensive care unit patients, a longitudinal study of the infant fecal microbiome, and a large autism spectrum project that is collecting microbiome samples from individuals with autism spectrum disorder and as many of their family members as possible. Though some associations with gut microbiota profiles are emerging, “We are still very young in understanding these communities,” said Mr. McDonald, a PhD candidate at the university.
Future goals include setting up the participant portal to enable better outreach to other countries. Currently, Mr. McDonald said, “a huge amount of diversity is being missed” by the project’s focus on samples from North America.”
Melanie Gareau, Ph.D., a physiologist with the College of Biological Sciences at the University of California, Davis, discussed her use of a mouse model to investigate the microbiota-gut-brain axis. The brain-gut relationship is bidirectional, but,Dr. Gareau said, microbiota clearly have an influence. Some gut variables, she said, include permeability, diet, and bacterial-host interactions. Variables within the brain and nervous system include the influence of such mediators as serotonin and other signaling molecules, such as brain-derived neurotrophic factor and the proto-oncogene c-Fos.
A central concept of gut physiology, said Dr. Gareau, is that the gut is bounded by a semipermeable membrane containing hundreds of millions of microbes. In humans, Dr. Gareau said, “Intestinal dysbiosis is increasingly recognized as a risk factor for disease development.” Emphasizing the bidirectional nature of the relationship, however, Dr. Gareau noted that stress is an external force that affects homeostasis; just as the hypothalamic-pituitary-adrenal axis can be regulated by the balance of microbiota, chronic stress can lead to changes in gut microbiota.
Dr. Gareau uses specialized breeds of mice, and also mice that have been bred and raised to be germ free, to observe the effect of manipulation of the gut microbiome on behavior. Mice that are infected with a murine-specific pathogen, she said, show impaired recognition and memory. When infected mice are exposed to stress, the negative impact on memory is intensified, and the effect persists after the infection has cleared. Related work shows that probiotic administration can improve behavior in wild-type mice.
Dr. Kirsten Tillisch, a gastroenterologist who is chief of integrative medicine at the University of California, Los Angeles, reminded attendees: “I am made up of more bug genes than I am human genes.” Further, she said, “Our microbiota signatures are very different between individuals. So it’s hard for us to get at ‘normal’ when studying humans.”
She noted that the interactions between the brain and the gut – and its resident microbiota – are made more complex in humans by our more advanced brains. Although animal models are incredibly useful because of the relative ease with which variables can be manipulated, she said, human research is still essential.
Calling for higher-quality research implementation and design in the field, Dr. Tillisch said neuroimaging shows potential to demonstrate anatomic and physiologic characteristics associated with particular gut microbial signatures; these can then be correlated with behavior and mood assessments.
In sum, “We carry around several pounds of organisms, Dr. Tillisch said. “It’s important not to neglect them and to treat them well.”
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