Abstract
The gut microbiome of long-lived people display an increasing abundance of subdominant species, as well as a rearrangement in health-associated bacteria, but less is known about microbiome functions. In order to disentangle the contribution of the gut microbiome to the complex trait of human longevity, we here describe the metagenomic change of the human gut microbiome along with aging in subjects with up to extreme longevity, including centenarians (aged 99 to 104 years) and semisupercentenarians (aged 105 to 109 years), i.e., demographically very uncommon subjects who reach the extreme limit of the human life span. According to our findings, the gut microbiome of centenarians and semisupercentenarians is more suited for xenobiotic degradation and shows a rearrangement in metabolic pathways related to carbohydrate, amino acid, and lipid metabolism. Collectively, our data go beyond the relationship between intestinal bacteria and physiological changes that occur with aging by detailing the shifts in the potential metagenomic functions of the gut microbiome of centenarians and semisupercentenarians as a response to progressive dietary and lifestyle modifications.IMPORTANCE The study of longevity may help us understand how human beings can delay or survive the most frequent age-related diseases and morbidities. In this scenario, the gut microbiome has been proposed as one of the variables to monitor and possibly support healthy aging. Indeed, the disruption of host-gut microbiome homeostasis has been associated with inflammation and intestinal permeability as well as a general decline in bone and cognitive health. Here, we performed a metagenomic assessment of fecal samples from semisupercentenarians, i.e., 105 to 109 years old, in comparison to young adults, the elderly, and centenarians, shedding light on the longest compositional and functional trajectory of the human gut microbiome with aging. In addition to providing a fine taxonomic resolution down to the species level, our study emphasizes the progressive age-related increase in degradation pathways of pervasive xenobiotics in Western societies, possibly as a result of a supportive process within the molecular continuum characterizing aging.
Highlights
IMPORTANCE The study of longevity may help us understand how human beings can delay or survive the most frequent age-related diseases and morbidities
Here we described—as far as we know, for the first time—the metagenomic changes of the human gut microbiota that occur with aging, up to extreme longevity, by characterizing the microbiome of semisupercentenarians, i.e., demographically very uncommon subjects who reach the extreme limit of the human life span (Ͼ105 years of age)
In addition to confirming the known taxonomic features of an aging microbiota, we extended the definition of the human core gut microbiota down to the species level and provided an accurate depiction of the functional changes occurring along with aging
Summary
IMPORTANCE The study of longevity may help us understand how human beings can delay or survive the most frequent age-related diseases and morbidities. Longevity has been described as the result of a complex combination of variables, deriving from genetics, lifestyle, and environment [1, 2] In this context, the intestinal microbiome has been proposed as a possible mediator of healthy aging that preserves host-environment homeostasis by counteracting inflammaging [3, 4], intestinal permeability [5], and deterioration of cognitive and bone health [5, 6]. According to our findings, aging is characterized by an increased number of genes involved in xenobiotic degradation, as well as by rearrangements in metabolic pathways related to carbohydrate, amino acid, and lipid metabolism These microbiome features are boosted even more in semisupercentenarians, probably representing the result of a lifelong remodeling response to progressive changes in diet and lifestyle
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