Mechanistic study of gut microbial biotransformation reactions and their physiological role.

The human gut microbiota, the trillions of microbes inhabiting our gastrointestinal tract, encodes an enormous number of metabolic enzymes, responsible for diverse biochemical reactions that determine metabolic microbiota-host interactions.

Bacterial biotransformation reactions, the chemical modification of compounds by bacteria, seem to play a central role in such metabolic interplay between the gut microbiota and its human host.

A number of gut microbial biotransformations such as reductive and hydrolytic reactions, as well as their metabolic enzymes, have been recently described.

The natural roles of these biotransformation pathways in bacterial metabolism and their influence on host physiology have been associated with gut bacterial fitness, nutrition uptake, immune signaling, as well as personal drug response and toxicity.

Despite these important functions, our mechanistic and physiological understanding remains still limited for many gut microbial biotransformation reactions, such as chemical conjugation.

To fill this knowledge gap, I present a multidisciplinary plan to systematically investigate conjugative biotransformation reactions of gut bacteria.

I will develop mass spectrometry-based methods to identify gut bacterial species and strains that perform conjugative biotransformations, employ high-throughput gut bacterial genetics to identify the responsible genes, determine their role in bacterial metabolism, and eventually assess selected examples for their impact on microbiota-host interactions in gnotobiotic mouse models.

If successful, this project will provide novel insights into gut microbial metabolism, and pave new ways to develop strategies for the rational manipulation of gut microbial community functions for better health outcomes.

Furthermore, this project will expand my professional network, transferrable skills, and scientific competencies, thus providing me the greatest opportunity to mature towards an independent scientist and investigator.