Inferring molecular mechanisms of host-microbe-drug interactions in the human gastrointestinal tract

Abstract

This study aimed to elucidate the metabolic interplay between food-borne bacteria, gut methanogens, and probiotic bacteria using the host-microbe-drug interactome. This study also aimed to identify suitable drug combinations that could effectively combat food-borne infections without adversely affecting the normal gut microbes. In this study, the system medicine framework comprised 2654 edges and 1609 nodes, with 1370 interacting human genes. Through network modeling analysis, we identified interactions among 39 human target genes for food-borne bacteria, 11 targets for gut methanogens, and nine targets for probiotic bacteria. Gut methanogens target common human genes for their pathophysiological functions. Linoleic acid has emerged as a crosstalk metabolite that determines the abundance of foodborne bacteria. Gut microbes commonly share butyric acid, CO₃, and formaldehyde as metabolic precursors. Most antibiotics interact with human genes that target the gut methanogens and probiotic bacteria. Our study identified fusidic acid, nabiximol, oxacillin, ampicillin, phenoxymethylpenicillin, and cefdinir as repurposable antibiotics against foodborne bacterial infections. Chloroquine, an antimalarial drug, has been suggested as a potential repurposable drug for foodborne infections, owing to its indirect association with many foodborne bacteria via host-mediated interactions. Thus, our system medicine framework could potentially aid in suggesting repurposable antibiotics against food-borne bacterial infections, without affecting beneficial microbes in the human gastrointestinal tract.