Gut Microbiota Modulation of Host Physiology and Drug Therapy
Intestines harbor trillions of microbes that have evolved through interactions among microbes as well as between host and microbes. The gut microbiome carries an enormous capacity to catalyze chemical reactions, but the identities and functions of their products remain unknown. Our current research focuses on how the small molecule metabolites produced by the gut microbiota modulate the host physiology by investigating the molecular mechanisms of action of these metabolites.
1. Phenylpropionic acid as a beneficial gut bacterial metabolite
We have found that a gut bacterial metabolite, phenylpropionic acid (PPA), confers protection against acetaminophen-induced liver injury and intestinal toxicity in mice. Acetaminophen overdose causes acute liver failure and intestinal toxicity due to the production of toxic metabolite by the hepatic drug-metabolizing enzyme CYP2E1. PPA supplementation decreased hepatic CYP2E1 protein levels. We are investigating the underlying molecular mechanisms and studying the potential benefits of PPA in improving gut health and preventing liver diseases.
2. Gut microbial metabolites as tumor progression agents
Fusobacterium nucleatum (Fn) is an opportunistic gut bacterium and has been known to be enriched in colorectal cancer (CRC) tissues, promoting CRC progression. However, mechanisms for Fn-promoted CRC progression remain fragmentary. In our unpublished study, we have found that Fn produces previously unknown metabolites that are essential for Fn-mediated promotion of CRC progression. Interestingly, the metabolites activate host (ligand-activated) transcription factors implicated in the promotion of cancer progression. We are investigating the roles of the Fn metabolites in promoting CRC progression.
3. Gut microbiota as a drug-metabolizing organ
The gut microbiota carries enzymes capable of drug biotransformation. However, the extent of impacts it has on drug therapy as well as the repertoire of bacterial genes and enzymes involved in the process remain incompletely understood. We investigate the bacterial factors responsible for the metabolism of anticancer drugs and immunosuppressants and the impacts of bacterial drug metabolism on drug therapy.