Abstract

Indole and phenol metabolites- small molecules that come from the breakdown of tryptophan, phenylalanine, and tyrosine- have significant physiological effects. Understanding the sources of these metabolites is crucial for designing effective therapeutic strategies to control their concentrations. Using stable isotope tracing together with gnotobiotic and antibiotic-treated mouse models, we re-examine the prevailing assumption that indole and phenol metabolites originate exclusively from gut microbial metabolism. Our results reveal substantial host contributions to the circulating pools of many of these metabolites.

For phenols that do require gut microbial input, we identify distinct upstream protein sources: host-secreted proteins (such as mucins) are the source for inflammatory phenols, while digestion-resistant dietary proteins are the source for phenols linked with healthy outcomes. We further demonstrate that targeted dietary interventions can selectively alter the circulating concentrations of these phenol classes by reshaping microbial access to their preferred protein substrates. Collectively, these studies highlight the importance of understanding the relative contributions of host and microbial metabolism to physiologically active metabolites.

Speaker Bio

Jenna AbuSalim is an MD/PhD trainee at Rutgers Robert Wood Johnson Medical School Princeton University, where she completed her PhD in Molecular Biology in the lab of Joshua D. Rabinowitz, MD, PhD. Her research in this lab focused on the biochemical interplay between diet, the gut microbiome, and host metabolism. Prior to her doctoral training, she conducted cancer metabolism research as a post-baccalaureate researcher at the National Cancer Institute and Emory University in the lab of Aparna Kesarwala, MD, PhD. She earned her undergraduate degree from Indiana University, completing a Bachelor of Science in Music with an outside field in Chemistry.