Shotgun Metagenomics of Gut Microbiota in Humans with up to Extreme Longevity and the Increasing Role of Xenobiotic Degradation

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.

Inflammaging in Endemic Areas for Infectious Diseases

“…Moreover, the gut microbiota of people characterized by extreme longevity, i.e. semi-supercentenarians (people who reached 105 years of age), show an increased capacity of xenobiotic degradation that likely contributes to their exceptional healthy aging ( 101 ). It is becoming clear that maintaining a health-associated microbiome is crucial to successful aging.…”

Association between alcohol consumption and oesophageal microbiota in oesophageal squamous cell carcinoma

“…Another recent study [ 23 ] revealed that some beneficial gut bacteria might be lost with age. Furthermore, Rampelli’s findings [ 24 ] demonstrated that the gut microbiome of the elderly population showed a rearrangement in metabolic pathways related to carbohydrate, amino acid, and lipid metabolism. Oakley and his colleagues [ 25 ] suggested that caecal microbial communities were greatly influenced by season of outgrowth.…”

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“…The presence of ARGs in these isolated villagers implies that ARGs are inherent features of the human microbiome. Although ARGs have been implicated as the inherent features of the human microbiome, albeit excessive antibiotic administration upsurges the acquisition, transmission, and dissemination of ARGs in the gut resistomes of different hosts [ 36 ]. Moreover, the antibiotic treatment causes the modification of gut resistome thereby leading to the predominance of resistant strains and their associated ARGs [ 37 , 38 ].…”