McGill University
Ph.D. candidate
Supervisor: Corinne Maurice
Start: 2017-09-01
End: 2021-04-30

Project

Gut bacterial physiology and activity along the progression to dysbiosis
During homeostasis, the gut microbiota provides many critical functions to the human host. Conversely, when the gut microbiota is in dysbiosis, it is correlated to a wide range of diseases. Dysbiosis is currently defined as a disease-specific shift in bacterial community diversity. A specific, functional-based description of dysbiosis is lacking, as well as the understanding of how the gut microbiota reaches this dysbiotic state. We hypothesize that there is a bacterial succession to dysbiosis where changes in bacterial physiology and activity occur before the onset of dysbiosis, specifically in the active bacterial population. These changes in bacterial physiology and activity are what lead to the change in community composition that is currently the endpoint of dysbiosis characterization. Using single-cell techniques such as fluorescently activated cell sorting and 16S sequencing (FACS-Seq), and bioorthogonal non-canonical amino acid tagging (BONCAT), we follow the dynamics of bacterial physiology and activity during the progression to dysbiosis. Specifically, we look at relative nucleic acid content, membrane damage, and translation. Our preliminary data show that upon dextran sodium sulphate (DSS) induced colitis in mice, changes in bacterial physiology occur on the same day as the onset of symptoms, which both precede the onset of dysbiosis. The active population of the gut microbiota is specifically enriched for Akkermansia muciniphila, highlighting the importance of low-abundant bacteria in promoting the disease state. Characterizing changes in bacterial physiology and activity during the progression of intestinal dysbiosis will allow for the identification of windows for successful therapeutic intervention.

Keywords

Human Gut Microbiota, bacterial physiology, flow cytometry, microbial ecology

Publications

1- The complex interplay of diet, xenobiotics, and microbial metabolism in the gut: Implications for clinical outcomes
Taguer, M, CF Maurice
2016 Clinical Pharmacology & Therapeutics