Background: Age-related physiological changes in the gastrointestinal tract, as well as modifications in lifestyle, nutritional behaviour, and functionality of the host immune system, inevitably affect the gut microbiota, resulting in a greater susceptibility to infections.

Methodology/principal findings: By using the Human Intestinal Tract Chip (HITChip) and quantitative PCR of 16S rRNA genes of Bacteria and Archaea, we explored the age-related differences in the gut microbiota composition among young adults, elderly, and centenarians, i.e subjects who reached the extreme limits of the human lifespan, living for over 100 years. We observed that the microbial composition and diversity of the gut ecosystem of young adults and seventy-years old people is highly similar but differs significantly from that of the centenarians. After 100 years of symbiotic association with the human host, the microbiota is characterized by a rearrangement in the Firmicutes population and an enrichment in facultative anaerobes, notably pathobionts. The presence of such a compromised microbiota in the centenarians is associated with an increased inflammatory status, also known as inflammageing, as determined by a range of peripheral blood inflammatory markers. This may be explained by a remodelling of the centenarians' microbiota, with a marked decrease in Faecalibacterium prauznitzii and relatives, symbiotic species with reported anti-inflammatory properties. As signature bacteria of the long life we identified specifically Eubacterium limosum and relatives that were more than ten-fold increased in the centenarians.

Conclusions/significance: We provide evidence for the fact that the ageing process deeply affects the structure of the human gut microbiota, as well as its homeostasis with the host's immune system. Because of its crucial role in the host physiology and health status, age-related differences in the gut microbiota composition may be related to the progression of diseases and frailty in the elderly population.