Shotgun Metagenomics of Human Gut Microbiota Up to Extreme Longevity and the Increasing Role of Xenobiotics Degradation

Longevity has been described as the result of a complex combination of variables, hailing from genetics, lifestyle and environment. In this context, the intestinal microbiome has been proposed as a possible mediator of healthy aging that preserves host-environment homeostasis by counteracting inflammaging, intestinal permeability, and deterioration of cognitive and bone health. Correlations have been previously found between age-related gut microbiota dysbioses and levels of pro-inflammatory cytokines, hospitalization, poor diet and frailty in the elderly. More recently, the longest human gut microbiota trajectory along aging has been built, by comparing the fecal bacterial taxa from healthy adults and older individuals, also including semi-supercentenarians, i.e. people aged 105 or older. However, the functional changes that occur in the gut microbiome along with age are still largely unexplored. In an attempt to provide some glimpses in this direction and advance our knowledge on whether and how the gut microbiome may support the maintenance of health in extreme aging, here we characterized the fecal microbiome of 62 individuals, with age ranging from 22 to 105 years, by shotgun metagenomics. According to our findings, aging is characterized by an increased number of genes involved in xenobiotics degradation, as well as by rearrangements in metabolic pathways related to carbohydrate, amino acid and lipid metabolism. These microbiome features are even more boosted in semi-supercentenarians, probably representing the result of a life-long adaptive response to progressive changes in diet and lifestyle.