The protective role of commensal gut microbes and their metabolites against bacterial pathogens.
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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
Gut Microbes 16 (1) 2356275 [2024-05-26; online 2024-05-26]
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.
PubMed 38797999
DOI 10.1080/19490976.2024.2356275
Crossref 10.1080/19490976.2024.2356275