{Reference Type}: Journal Article
{Title}: The protective role of commensal gut microbes and their metabolites against bacterial pathogens.
{Author}: Cheng L;Correia MSP;Higdon SM;Romero Garcia F;Tsiara I;Joffré E;Sjöling Å;Boulund F;Norin EL;Engstrand L;Globisch D;Du J;
{Journal}: Gut Microbes
{Volume}: 16
{Issue}: 1
{Year}: 2024 Jan-Dec
{Factor}: 9.434
{DOI}: 10.1080/19490976.2024.2356275
{Abstract}: 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.