Speaker: Dr. Alban Gaultier, Ph.D. from University of Virginia
Title: “Effect of gut microbes on mood and anxiety”
Dr. Alban Gaultier is an Assistant Professor at the University of Virginia. To study the effect of the microbiome on depression and anxiety, Dr. Gaultier’s lab used the unpredictable chronic mild stress (UCMS) protocol to induce a depressive phenotype in mice. In work published in Scientific Reports this year, they showed the UCMS protocol does not change the total amount of microbiota present in the gut. Rather, it drives dysbiosis, reducing the population of Lactobacillus species in the gut across multiple strains of mice. Further, they found that replacing the lost species with Lactobacillus reuteri improved the depressive phenotype. They then delved into the pathogenesis of these findings.
Using metabolomics, they found an increase in products of the tryptophan kynurenine pathway in depressed mice. They reasoned that Lactobacillus generate reactive oxygen species, and these reactive species inhibit the enzyme IDO1, responsible for converting tryptophan to kynurenine. They hypothesized that reduced Lactobacillus species can cause increased levels of kynurenine, which is able to cross the blood brain barrier and contribute to depressive symptoms. To confirm this hypothesis, they found that augmenting kynurenine levels abolished the beneficial effect of Lactobacillus supplementation. Since the publication of their paper this year, Dr. Gaultier’s lab has been asking the question: how does the UCMS protocol change the microbiome?
Their first hypothesis was that the adaptive immune system could be contributing to this change, but they observed the same decrease in Lactobacillus in mice without an adaptive immune system. Further investigation showed that stressed mice have increased colonic motility; and because Lactobacillus are scavengers, they hypothesized that the reduced transit time in the colon caused the Lactobacillus to be outcompeted. Their data show that not only does administering a laxative reduce Lactobacillus species, but also it drives depressive behavior in mice.
Finally, they have been investigating the effect of the kynurenine pathway on oligodendrocytes, the glial cells of the CNS, as a reduction of glial cells can be found in the brains of depressed patients. Preliminary data shows that increased levels of kynurenine reduces the survival of oligodendrocyte progenitor cells and inhibits their differentiation. In summary, Dr. Gaultier and his lab has revealed a mechanism by which the microbiome, specifically Lactobacillus species, can contribute to anxiety and depression.