Biology subjects

Chankhamjon, P.

Publications and source records attributed to Chankhamjon, P..

2 recordsLinked to original sources

bioRxiv2024

A meta-analysis of the gut microbiome in inflammatory bowel disease patients identifies disease-associated small molecules

Changes in the gut microbiome have been associated with several human diseases, but the molecular and functional details underlying these associations remain largely unknown. Here, we performed a multi-cohort analysis of small molecule biosynthetic gene clusters (BGCs) in 5,306 metagenomic samples of the gut microbiome from 2,033 Inflammatory Bowel Disease (IBD) patients and 833 matched healthy subjects and identified a group of Clostridia-derived BGCs that are significantly associated with IBD. Using synthetic biology, we discovered and solved the structures of six fatty acid amides as the products of the IBD-enriched BGCs. Using two mouse models of colitis, we show that the discovered small molecules disrupt gut permeability and exacerbate inflammation in chemically and genetically susceptible mice. These findings suggest that microbiome-derived small molecules may play a role in the etiology of IBD and represent a generalizable approach for discovering molecular mediators of microbiome-host interactions in the context of microbiome-associated diseases.

microbiology↗

bioRxiv2019

Systematic mapping of drug metabolism by the human gut microbiome

The human gut microbiome harbors hundreds of bacterial species with diverse biochemical capabilities, making it one of natures highest density, highest diversity bioreactors. Several drugs have been previously shown to be directly metabolized by the gut microbiome, but the extent of this phenomenon has not been systematically explored. Here, we develop a systematic screen for mapping the ability of the complex human gut microbiome to biochemically transform small molecules (MDM-Screen), and apply it to a library of 575 clinically used oral drugs. We show that 13% of the analyzed drugs, spanning 28 pharmacological classes, are metabolized by a single microbiome sample. In a proof-of-principle example, we show that microbiome-derived metabolism occurs in vivo, identify the genes responsible for it, and provide a possible link between its consequences and clinically observed features of drug bioavailability and toxicity. Our findings reveal a previously underappreciated role for the gut microbiome in drug metabolism, and provide a comprehensive framework for characterizing this important class of drug-microbiome interactions.

microbiology↗