Tryptophan-metabolizing gut microbes regulate adult neurogenesis via the aryl hydrocarbon receptor.

While modulatory effects of gut microbes on neurological phenotypes have been reported, the mechanisms remain largely unknown. Here, we demonstrate that indole, a tryptophan metabolite produced by tryptophanase-expressing gut microbes, elicits neurogenic effects in the adult mouse hippocampus. Neurogenesis is reduced in germ-free (GF) mice and in GF mice monocolonized with a single-gene tnaA knockout (KO) mutant Escherichia coli unable to produce indole. External administration of systemic indole increases adult neurogenesis in the dentate gyrus in these mouse models and in specific pathogen-free (SPF) control mice. Indole-treated mice display elevated synaptic markers postsynaptic density protein 95 and synaptophysin, suggesting synaptic maturation effects in vivo. By contrast, neurogenesis is not induced by indole in aryl hydrocarbon receptor KO (AhR-/-) mice or in ex vivo neurospheres derived from them. Neural progenitor cells exposed to indole exit the cell cycle, terminally differentiate, and mature into neurons that display longer and more branched neurites. These effects are not observed with kynurenine, another AhR ligand. The indole-AhR-mediated signaling pathway elevated the expression of ß-catenin, Neurog2, and VEGF-α genes, thus identifying a molecular pathway connecting gut microbiota composition and their metabolic function to neurogenesis in the adult hippocampus. Our data have implications for the understanding of mechanisms of brain aging and for potential next-generation therapeutic opportunities.

Lifestyle factors associated with poor sleep quality among undergraduate dental students at a Malaysian private university.

Objective: The purpose of this study was to look into the associations between lifestyle factors, gender, clinical level, and sleep quality among undergraduate dental students at a private university in Malaysia. Material and Methods: A self-administered Pittsburg sleep quality index (PSQI) scale and the lifestyle and habits questionnaire-brief (LHQ-B) were used in this cross-sectional study. A global PSQI score of greater than 5 indicates poor sleep quality. All university dental students were invited to take part. Descriptive statistics and logistic regression analyses were used to analyze the data. Results: A total of 338 students took part in the study, with a response rate of 90.4%. The proportion of females was higher (68.3 %) and more than half of the respondents (56.7 %) were in their clinical years. The prevalence of poor sleep quality was 36.7%. At multivariable level, poor sleep quality was associated with being male (OR=1.72 [95% confidence interval (1.05, 2.83)] and engaging in an unhealthy lifestyle for psychological health (OR=2.64 [95% confidence interval (1.34, 5.21)] and nutrition (OR=2.48 [95% confidence interval (1.028, 4.82)]. Conclusion: The prevalence of poor sleep quality among undergraduate dental students in our study was comparable to that found in other studies. Male students were more likely to have poor sleep quality than female students. Our findings indicate that poor sleep quality (PSQI score >5) may be linked to unhealthy lifestyle habits related to psychological health and nutrition. Health education that emphasizes these domains is essential for improving their lifestyle habits and sleep quality.