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              Advocacy & Research for Unlimited Lifespans


A Cross-Sectional Study of Compositional and Functional Profiles of Gut Microbiota in Sardinian Centenarians

centenarian gut microbiota longevity metagenomic sequencing

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#1 Engadin

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Posted 28 August 2019 - 11:38 PM




S O U R C E :   American Journal for Microbiology







Sardinia, Italy, has a high prevalence of residents who live more than 100 years. The reasons for longevity in this isolated region are currently unknown. Gut microbiota may hold a clue. To explore the role gut microbiota may play in healthy aging and longevity, we used metagenomic sequencing to determine the compositional and functional differences in gut microbiota associated with populations of different ages in Sardinia. Our data revealed that the gut microbiota of both young and elderly Sardinians shared similar taxonomic and functional profiles. A different pattern was found in centenarians. Within the centenarian group, the gut microbiota was correlated with the functional independence measurement of the host. Centenarians had a higher diversity of core microbiota species and microbial genes than those in the young and elderly. We found that the gut microbiota in Sardinian centenarians displayed a rearranged taxonomic pattern compared with those of the young and elderly, featured by depletion of Faecalibacterium prausnitzii and Eubacterium rectale and enriched for Methanobrevibacter smithii and Bifidobacterium adolescentis. Moreover, functional analysis revealed that the microbiota in centenarians had high capacity for central metabolism, especially glycolysis and fermentation to short-chain fatty acids (SCFAs), although the gut microbiota in centenarians was low in genes encoding enzymes involved in degradation of carbohydrates, including fibers and galactose.





The gut microbiota has been proposed as a promising determinant for human health. Centenarians as a model for extreme aging may help us understand the correlation of gut microbiota with healthy aging and longevity. Here we confirmed that centenarians had microbiota elements usually associated with benefits to health. Our finding of a high capacity of glycolysis and related SCFA production represented a healthy microbiome and environment that is regarded as beneficial for host gut epithelium. The low abundance of genes encoding components of pathways involved in carbohydrate degradation was also found in the gut microbiota of Sardinian centenarians and is often associated with poor gut health. Overall, our study here represents an expansion of previous research investigating the age-related changes in gut microbiota. Furthermore, our study provides a new prospective for potential targets for gut microbiota intervention directed at limiting gut inflammation and pathology and enhancing a healthy gut barrier.





Longevity is a complex biological phenotype determined by genetic, epigenetic, and environmental factors such as diet, lifestyle, and even geographic location (14). These factors have also been shown to affect the gut microbiota in humans (58). It has been demonstrated that gut microbiota is tightly linked to human health and disease (9). There is evidence showing that the gut microbiome contributes to the regulation of host life span in animal models, such as Caenorhabditis elegansNothobranchius furzeri (turquoise killifish), Heterocephalus glaber (naked mole-rat) and Drosophila (1013). Moreover, a longitudinal study has also found association between the distinct metabolomic signatures and longevity of humans (14). Thus, gut microbiota may also modulate human longevity by affecting the host metabolism. Manipulating the gut microbiota with diet intervention and calorie restriction (CR) has potential therapeutic applications for pro-healthy aging intervention (415).


Several groups have used centenarians as a model to study aging and gut microbiota (1622), with most studies focusing on the compositional features of gut microbiota. Even though a few studies have examined the metabolic function of gut microbiota in centenarians (182223), metagenomic analysis of metabolic functions has yet to be fully explored in diverse populations from various geographic regions. The Mediterranean island of Sardinia is well-known for the unique isolated genomic background and the high prevalence of centenarians (22425). The high prevalence of centenarians, consistent lifestyle, and low immigration rates make Sardinia an ideal geographic area for the study of longevity. However, little is known about how the Sardinian environment and genetic factors influence the gut microbiota in Sardinian centenarians (2629). Surveying the gut microbiota in Sardinian centenarians may also expand our understanding of longevity across global populations.


Here we performed a cross-sectional survey of the gut microbiota in the longevity-prone population in Sardinia by metagenomic sequencing. In our study, we recruited 65 subjects, divided into three age groups: the young, elderly, and centenarians. We obtained the taxonomic composition and functional annotation of the gut microbiota in the different age groups. We also correlated health status with gut microbiota in centenarians.





Characterization of gut microbiota compositional profiles in the three age groups.To obtain the taxonomic compositional and functional profiles of gut microbiota in the Sardinian population, we recruited a cohort of three age groups: healthy young (n = 19), healthy elderly (n = 25), and centenarians (n = 21). The clinical characteristics are shown in Table 1 and Table S1 in the supplemental material. A total of 59 qualified stool samples were used to extract microbial DNA for DNA library construction and shotgun metagenomic sequencing. On average, 5.8 Gb data (approximately 41.3 million high-quality clean reads) were generated per sample. Human contamination was removed (on average, up to 14% of the total reads) before further processing. The taxonomic compositional profile was generated using MetaPhlAn2 (30). We verified our results using the IGC database (31). The workflow is shown in Fig. S1 in the supplemental material.







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Also tagged with one or more of these keywords: centenarian, gut microbiota, longevity, metagenomic, sequencing

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