Exercise-driven gut microbiota alterations enhance colonization resistance against methicillin-resistant Staphylococcus aureus

Highlights•Moderate exercise enhances gut colonization resistance against MRSA in mice•D. newyorkensis (L8) is the key bacterium mediating increased colonization resistance•Probiotic strain L8 thwarts MRSA colonization by competing for carbon source fucoseSummaryGut microbiota plays a crucial role in resisting the invasion of pathogens, particularly multidrug-resistant (MDR) bacteria, which pose a significant threat to public health. While exercise offers numerous health benefits, its impact on host colonization resistance remains largely unclear. In this study, we demonstrate that moderate exercise significantly reduces gut colonization by methicillin-resistant Staphylococcus aureus (MRSA), a clinically important MDR pathogen. Moreover, we identify an understudied strain of the intestinal probiotic Dubosiella newyorkensis (L8) as a critical factor in mediating exercise-induced colonization resistance against MRSA. Mechanistically, L8 enhances the deprivation of fucose, a crucial carbon source essential for MRSA growth and pathogenicity. This process relies on the high binding affinity of pyruvate to the ILE257 site of the lactate dehydrogenase in L8. Overall, our work highlights the importance of moderate exercise in maintaining host colonization resistance and demonstrates L8 as a probiotic in protecting against MRSA colonization.Graphical abstract