Identification of unique bile acid metabolizing bacteria from the microbiome of centenarians

Centenarians, who are living more than a century, represent the ultimate model of successful longevity associated with less susceptibility to aging-associated illness and chronic inflammation. The gut microbiota has been considered as a criticial determinant for human health and longevity. Here we show that centenarians (average 107 yo) have distinct gut microbiome enriched in microbes capable of generating unique secondary bile acids, include iso-,3-oxo, and iso-allo-lithocolic acid (LCA), as compared to elderly (85-89 yo) and young (21-55 yo) controls. In particular, iso-allo-LCA biosysnthesis pathway had not been defined. By screening of 68 bacterial isolates from a centenarian's faecal microbiota, we identified Paraceteroides merdae and Odoribacteraceae stains as effective producers of iso-all-LCA. Furthermore, we revealed that 5'-reductase (5AR) and 3'-hydroxysteroid dehydrogenase (3'HSDH) were responsible for the iso-allo-LCA generation by generating and testing mutant P. merdae strains. Iso-allo-LCA exerted the most potent antimicrobial effects among the test bile acid compounds, against gram-positive (but not gram-negative) multidrug-resistant pathogens, such as Clostridium difficile and vancomycin-resitant Enterococcus faecium. These findings suggest that specific bile acid metabolism may be involved in reducing the risk of acquiring pathobionts and their related diseases, thereby potentially contributing to longevity.