Gut microbiota as an antioxidant system in centenarians associated with high antioxidant activities of gut-resident Lactobacillus

The gut microbiota plays an important role in human health and longevity, and the gut microbiota of centenarians shows unique characteristics. Nowadays, most microbial research on longevity is usually limited to the bioinformatics level, lacking validating information on culturing functional microorganisms. Here, we combined metagenomic sequencing and large-scale in vitro culture to reveal the unique gut microbial structure of the world’s longevity town—Jiaoling, China, centenarians and people of different ages. Functional strains were isolated and screened in vitro, and the possible relationship between gut microbes and longevity was explored and validated in vivo. 247 healthy Cantonese natives of different ages participated in the study, including 18 centenarians. Compared with young adults, the gut microbiota of centenarians exhibits higher microbial diversity, xenobiotics biodegradation and metabolism, oxidoreductases, and multiple species (the potential probiotics Lactobacillus, Akkermansia, the methanogenic Methanobrevibacter, gut butyrate-producing members Roseburia, and SCFA-producing species uncl Clostridiales, uncl Ruminococcaceae) known to be beneficial to host metabolism. These species are constantly changing with age. We also isolated 2055 strains from these samples by large-scale in vitro culture, most of which were detected by metagenomics, with clear complementarity between the two approaches. We also screened an age-related gut-resident Lactobacillus with independent intellectual property rights, and its metabolite (L-ascorbic acid) and itself have good antioxidant effects. Our findings underscore the existence of age-related trajectories in the human gut microbiota, and that distinct gut microbiota and gut-resident as antioxidant systems may contribute to health and longevity.