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

Abstract

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. IMPORTANCE 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.

Age-Related Variation of Bacterial and Fungal Communities in Different Body Habitats across the Young, Elderly, and Centenarians in Sardinia

“…We observed that the young and elderly had similar bacterial gut community compositions, consistent with previous studies (21,27), but different from the bacterial gut community composition of most of the centenarians. Similar results were also obtained by our previous metagenomics sequencing (28), as well as the results from an Emilia-Romagna (Italy) cohort and a Japanese cohort (24,26). The separated clustering of the gut bacterial communities in the centenarians across populations suggested that age shaped the gut bacterial community following the same trajectory with the aging process.…”

“…Aging-related alterations in the gut bacterial community in different cohorts have been demonstrated in previous studies (20)(21)(22)(23)(24)(25)(26)(27)(28). The variation may be caused by diverse genetic, dietary, and environmental factors (29)(30)(31)(32).…”

Multi-omic analysis reveals the anti-aging impact of sulforaphane on the microbiome and metabolome

“…Interestingly, L-lysine is an essential ketogenic amino acid and critical building block for proteins. An increase in L-lysine in the human gut was also observed in young compared to centenarian and elderly groups [49]. Our metabolic pathway analysis was done with inferred functional profiles.…”

“…Noticeably, the TCA cycle, one of the essential functions of mitochondria [48] and a central hub for energy metabolism and macromolecule synthesis, and pyruvate fermentation to propanoate I were significantly enriched in the old control group. A comparison study of the human gut microbiota between centenarian, elderly and young individuals, based on the premise that centenarians are a model of healthy aging, identified these two metabolic pathways enriched in the centenarian group compared to the young and elderly groups [49]. Since pyruvate is the major precursor for the synthesis of three major SCFAs, acetate, propionate, and butyrate that are related to a strong gut epithelium, this study interpreted the enrichment of the TCA cycle and pyruvate fermentation to propanoate I as a signature of longevity and healthy microbiome.…”

Metagenomic analysis of gut microbiota in Parkinson's disease patients from Central China

“…Raw data was rst evaluated by FastQC (version 0.11.8) and mapped against the human genome (hg38) from University of California Santa Cruz (UCSC) with Bowtie2 (version 2.3.5.1), reads aligned to the human genome were removed, and ltered clean reads were used for further analysis. Subsequent analysis was performed as previous study described [44]. Gut microbiotal composition were predicted using MetaPhlan2.0 [45] (version 2.7.7), GraPhlAn (version 0.97) was used to construct the Phylogenetic tree.…”