Serum metabolic and microbial profiling yields insights into promoting effect of tryptophan‐related metabolites for health longevity in centenarians

A better understanding of the characteristic serum metabolites and microbiota from the gut and oral cavity in centenarians could contribute to elucidating the mutual connections among them and would help provide information to achieve healthy longevity. Here, we have recruited a total of 425 volunteers, including 145 centenarians in Suixi county - the first certified "International Longevity and Health Care Base" in China. An integrative analysis for the serum metabolites, gut, and oral microbiota of centenarians (aged 100-120) was compared with those of centenarians' lineal relatives (aged 24-86), the elderly (aged 65-88) and young (aged 23-54). Strikingly distinct metabolomic and microbiological profiles were observed within the centenarian signature, longevity family signature, and aging signature, underscoring the metabolic and microbiological diversity among centenarians and their lineal relatives. Within the centenarian between healthy and frail individuals, significant differences in metabolite profiles and microbiota compositions are observed, suggesting that healthy longevity is associated with unique metabolic and microbiota patterns. Through an integrative analysis, the tryptophan pathway has been revealed to be an important potential mechanism for individuals to achieve healthy longevity. Specifically, a key tryptophan metabolite, 5-methoxyindoleacetic acid (5-MIAA), was revealed to be associated with the genus <i>Christensenellaceae</i> R-7 group, and it exhibited effects of delaying cell senescence, promoting lifespan, and alleviating inflammation. Our characterization of the extensive metabolomic and microbiota remodeling in centenarians may offer new scientific insights for achieving healthy longevity.