%0 Journal Article
%T The protective role of commensal gut microbes and their metabolites against bacterial pathogens.
%A Cheng L
%A Correia MSP
%A Higdon SM
%A Romero Garcia F
%A Tsiara I
%A Joffré E
%A Sjöling Å
%A Boulund F
%A Norin EL
%A Engstrand L
%A Globisch D
%A Du J
%J Gut Microbes
%V 16
%N 1
%D 2024 Jan-Dec
%M 38797999
%F 9.434
%R 10.1080/19490976.2024.2356275
%X Multidrug-resistant microorganisms have become a major public health concern around the world. The gut microbiome is a gold mine for bioactive compounds that protect the human body from pathogens. We used a multi-omics approach that integrated whole-genome sequencing (WGS) of 74 commensal gut microbiome isolates with metabolome analysis to discover their metabolic interaction with Salmonella and other antibiotic-resistant pathogens. We evaluated differences in the functional potential of these selected isolates based on WGS annotation profiles. Furthermore, the top altered metabolites in co-culture supernatants of selected commensal gut microbiome isolates were identified including a series of dipeptides and examined for their ability to prevent the growth of various antibiotic-resistant bacteria. Our results provide compelling evidence that the gut microbiome produces metabolites, including the compound class of dipeptides that can potentially be applied for anti-infection medication, especially against antibiotic-resistant pathogens. Our established pipeline for the discovery and validation of bioactive metabolites from the gut microbiome as novel candidates for multidrug-resistant infections represents a new avenue for the discovery of antimicrobial lead structures.