Consistent signatures in the human gut microbiome of longevous populations.

Gut microbiota of centenarians has garnered significant attention in recent years, with most studies concentrating on the analysis of microbial composition. However, there is still limited knowledge regarding the consistent signatures of specific species and their biological functions, as well as the potential causal relationship between gut microbiota and longevity. To address this, we performed the fecal metagenomic analysis of eight longevous populations at the species and functional level, and employed the Mendelian randomization (MR) analysis to infer the causal associations between microbial taxa and longevity-related traits. We observed that several species including , , , and were consistently enriched in the gut microbiota of long-lived individuals compared to younger elderly and young adults across multiple cohorts. Analysis of microbial pathways and enzymes indicated that plays a role in the protein -glycosylation, while is involved in the 3-dehydroquinate and chorismate biosynthesis. Furthermore, makes a distinct contribution to the purine nucleobase degradation I pathway, potentially assisting the elderly in maintaining purine homeostasis. contributes to the menaquinone (vitamin K2) biosynthesis, which may help prevent age-related diseases such as osteoporosis-induced fractures. According to MR results, was significantly positively correlated with parental longevity, and also exhibited positive associations with lifespan and multiple traits related to parental longevity. Additionally, and were consistently enriched in the gut microbiota of the three largest cohorts of long-lived individuals, and MR analysis also suggests their potential causal relationships with longevity. Our findings reveal longevity-associated gut microbial signatures, which are informative for understanding the role of microbiota in regulating longevity and aging.