A Cross-sectional study of diverse bacterial and fungal communities in different body habitats in Sardinian centenarians

Microbes in the human body co-evolved with the host during the aging process, adapting to the aging-related niche alternation, however, the full view of the human microbiota variation related to aging is still unknown. Besides, the gut microbiota has been proposed as a promising determinant for human health. Using centenarians as a model for extreme aging may help to understand the correlation of gut microbiota with healthy-aging and longevity. By recruiting the young, elderly and centenarians in Sardinia, Italy, we obtained an integrated view of the spatial distribution of microbiota in the human body across a wide age range and determined the compositional and functional differences in gut microbiota associated with populations of different age in Sardinia. We found that the distribution and correlation of bacteria and fungi community in Sardinians were driven by body sites. In each different age groups, both the bacterial and fungal communities in the skin were significantly different in structure, but not in the oral. The gut bacterial communities in the centenarians clustered separately from the young and elderly which had overlapped clustering, while the fungal communities in gut can’t be separated by the age groups. Moreover, our data revealed that gut microbiota of the healthy elderly and young Sardinians also shared similar metabolic functional profiles, while a distinct cluster is found in centenarians. Within the centenarian group, the gut microbiota is correlated with health status of the host. The centenarians have higher diversity of core microbiota species and microbes genes compared with that in young and elderly. The enrichment of Methanobrevibacter and Bifidobacterium were detected in Sardinian centenarians, which were also verified in a bigger centenarian cohort in Bologna, Italy. Moreover, potential metabolic functional analysis revealed that the gut microbiota in the centenarian group had significantly lower capability to digest complex carbohydrates but had enhanced fermentation capability via glycolysis. Gene pathways involved in amino acid biosynthesis are lower abundance, while menaquinol biosynthesis is higher abundance in the centenarians compared with that of the young and elderly. Our study indicates that the critical role aging plays in shaping human microbiota is habitat dependent, further suggesting the diverse degree of niche alternation caused by aging in different body habitats, emphasizing the importance of integrating the potential confounding factors into the microbiota studies. Sardinian centenarians’ specific gut microbiota may hold promising clues for the future research to identify the possible causative relationship between gut microbiota and longevity in human.