Sarkis Mazmanian
Luis & Nelly Soux Professor of Microbiology
California Institute of Technology
Sarkis Mazmanian is the Luis & Nelly Soux Professor of Microbiology at Caltech. He was a Phi Beta Kappa graduate from UCLA, where Dr. Mazmanian also received his PhD training in microbiology and immunology. He was awarded a Helen Hay Whitney Postdoctoral Fellowship at Harvard Medical School, before moving to Caltech. Dr. Mazmanian has won numerous awards including the MacArthur Foundation “Genius” award. His laboratory studies the biology of the human gut microbiome. He is a co-founder of 3 biotech companies, and serves on the Scientific Advisory Board of over a dozen companies, academic centers and foundations.
abstract
Gut Bacteria Molecules Mediate Emotional Behaviors in Mice
The microbiome can influence behavior via gut-brain interactions that remain largely undescribed. We previously identified a microbial metabolite, 4-ethylphenyl sulfate (4EPS), that is elevated in a mouse model of altered neurodevelopment. Here, we engineered gut bacteria to selectively produce 4EPS and uncovered changes in brain activity and functional connectivity in brain regions linked to emotional behavior, as well as gene expression signatures of altered oligodendrocyte function. Indeed, production of 4EPS by the microbiome was associated with increased proportions of immature oligodendrocytes and, accordingly, decreased myelination of neuronal axons in the brain. Furthermore, mice exposed to 4EPS displayed anxiety-like behaviors. Pharmacologic treatment promoted oligodendrocyte differentiation and reversed the behavioral effects of 4EPS. These findings reveal that a gut microbial molecule can impact the function of brain cells and modulate complex behaviors in mice.