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Brain Structure and Response to Emotional Stimuli as Related to Gut Microbial Profiles in Healthy Women

Tillisch, Kirsten MD; Mayer, Emeran A. MD, PhD; Gupta, Arpana PhD; Gill, Zafar BSc; Brazeilles, Rémi MSc; Le Nevé, Boris PhD; van Hylckama Vlieg, Johan E.T. PhD; Guyonnet, Denis PhD; Derrien, Muriel PhD; Labus, Jennifer S. PhD

doi: 10.1097/PSY.0000000000000493

Objective Brain-gut-microbiota interactions may play an important role in human health and behavior. Although rodent models have demonstrated effects of the gut microbiota on emotional, nociceptive, and social behaviors, there is little translational human evidence to date. In this study, we identify brain and behavioral characteristics of healthy women clustered by gut microbiota profiles.

Methods Forty women supplied fecal samples for 16S rRNA profiling. Microbial clusters were identified using Partitioning Around Medoids. Functional magnetic resonance imaging was acquired. Microbiota-based group differences were analyzed in response to affective images. Structural and diffusion tensor imaging provided gray matter metrics (volume, cortical thickness, mean curvature, surface area) as well as fiber density between regions. A sparse Partial Least Square-Discrimination Analysis was applied to discriminate microbiota clusters using white and gray matter metrics.

Results Two bacterial genus-based clusters were identified, one with greater Bacteroides abundance (n = 33) and one with greater Prevotella abundance (n = 7). The Prevotella group showed less hippocampal activity viewing negative valences images. White and gray matter imaging discriminated the two clusters, with accuracy of 66.7% and 87.2%, respectively. The Prevotella cluster was associated with differences in emotional, attentional, and sensory processing regions. For gray matter, the Bacteroides cluster showed greater prominence in the cerebellum, frontal regions, and the hippocampus.

Conclusions These results support the concept of brain-gut-microbiota interactions in healthy humans. Further examination of the interaction between gut microbes, brain, and affect in humans is needed to inform preclinical reports that microbial modulation may affect mood and behavior.

Supplemental digital content is available in the text.

From the Oppenheimer Center for Neurobiology of Stress and Resilience (Tillisch, Mayer, Gupta, Gill, Labus), Departments of Medicine (Tillisch, Mayer, Gupta, Labus), Psychiatry (Mayer, Gupta), Division of Digestive Diseases, David Geffen School of Medicine at UCLA (Tillisch, Mayer, Gupta, Labus), UCLA Microbiome Center, Ahmanson-Lovelace Brain Mapping Center, UCLA (Mayer), Integrative Medicine, GLA VHA (Tillisch), UCLA Brain Research Institute (Labus), Los Angeles, CA; Danone Research (Brazeilles, Le Nevé, Derrien), Palaiseau, France; Microbiome & Human Health Innovation (van Hylckama Vlieg), Hoersholm, Denmark; and Symrise Group (Guyonnet), Clichy-la-Garenne, France.

Supplemental Content

Address correspondence and reprint requests to Kirsten Tillisch, MD, Integrative Medicine, GLA VHA, Oppenheimer Center for Neurobiology of Stress and Resilience, Division of Digestive Diseases, David Geffen School of Medicine at UCLA, Center for Life Sciences, 10833 Le Conte Avenue, Los Angeles, CA 90095. E-mail:

Received for publication April 15, 2016; revision received February 2, 2017.

Copyright © 2017 by American Psychosomatic Society
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