Isolated human gut anaerobes produce metabolites antagonistic to MDR pathogens. Commensal gut microbes and their metabolites inhibit bacterial pathogen growth

Multidrug resistant microorganisms have become a major public health concern around the world. The gut microbiome is a goldmine of bioactive compounds that protect the human body from pathogens. In this study, we used a multi-omics approach that integrated whole genome sequencing (WGS) of 74 commensal gut microbiome isolates with matched, cutting-edge metabolome analysis for each isolate to discover their metabolic interaction with Salmonella and other antibiotic-resistant pathogens. We identified the top altered metabolites in co-culture supernatants of chosen commensal gut microbiome isolates in comparison to the supernatant of Salmonella growth cultures. The verified metabolites were then examined for their ability to prevent the growth of various antibiotic-resistant bacteria (Salmonella Enteritidis, Salmonella Typhimurium, Staphylococcus aureus, Escherichia coli, and Klebsiella pneumoniae). Furthermore, we evaluated differences in the functional potential among the selected isolates based on WGS annotation profiles. Our findings provide compelling evidence that the gut microbiome produces metabolites that could potentially be applied for anti-infection medicines, especially against antibiotic-resistant pathogens. We also established a pipeline for the discovery and validation of the metabolites from the gut microbiome as novel candidates for multidrug resistant infections.