Centenarians are an excellent model to study the relationship between the gut microbiome and longevity. To characterize the gut microbiome signatures of aging, we conducted a cross-sectional investigation of 1,575 individuals (20-117 years) from Guangxi province of China, including 297 centenarians (n = 45 with longitudinal sampling). Compared to their old adult counterparts, centenarians displayed youth-associated features in the gut microbiome characterized by an over-representation of a Bacteroides-dominated enterotype, increase in species evenness, enrichment of potentially beneficial Bacteroidetes and depletion of potential pathobionts. Health status stratification in older individuals did not alter the directional trends for these signature comparisons but revealed more apparent associations in less healthy individuals. Importantly, longitudinal analysis of centenarians across a 1.5-year period indicated that the youth-associated gut microbial signatures were enhanced with regard to increased evenness, reduction in interindividual variation and stability of Bacteroides, and that centenarians with low microbial evenness were prone to large microbiome instability during aging. These results together highlight a youth-related aging pattern of the gut microbiome for long-lived individuals. 

Longevity of centenarians is reflected by the gut microbiome with youth-associated signatures

Gut OncoMicrobiome Signatures (GOMS) as next-generation biomarkers for cancer immunotherapy.

The gut microbiota plays an important role in human health and longevity, and the gut microbiota of centenarians shows unique characteristics. Nowadays, most microbial research on longevity is usually limited to the bioinformatics level, lacking validating information on culturing functional microorganisms. Here, we combined metagenomic sequencing and large-scale in vitro culture to reveal the unique gut microbial structure of the world's longevity town-Jiaoling, China, centenarians and people of different ages. Functional strains were isolated and screened in vitro, and the possible relationship between gut microbes and longevity was explored and validated in vivo. 247 healthy Cantonese natives of different ages participated in the study, including 18 centenarians. Compared with young adults, the gut microbiota of centenarians exhibits higher microbial diversity, xenobiotics biodegradation and metabolism, oxidoreductases, and multiple species (the potential probiotics Lactobacillus, Akkermansia, the methanogenic Methanobrevibacter, gut butyrate-producing members Roseburia, and SCFA-producing species uncl Clostridiales, uncl Ruminococcaceae) known to be beneficial to host metabolism. These species are constantly changing with age. We also isolated 2055 strains from these samples by large-scale in vitro culture, most of which were detected by metagenomics, with clear complementarity between the two approaches. We also screened an age-related gut-resident Lactobacillus with independent intellectual property rights, and its metabolite (L-ascorbic acid) and itself have good antioxidant effects. Our findings underscore the existence of age-related trajectories in the human gut microbiota, and that distinct gut microbiota and gut-resident as antioxidant systems may contribute to health and longevity. 

/pdf/gut-microbiota-as-an-antioxidant-system-in-centenarians-24qxdamv.pdf

Gut microbiota as an antioxidant system in centenarians associated with high antioxidant activities of gut-resident Lactobacillus

The intestinal microbiome modulates the risk of several age-related chronic diseases and syndromes, including frailty and neurodegenerative diseases. Herein we provided an update on the influence of gut microbiota on physical and cognitive performance in older age and suggest microbiota-targeted interventions for healthy ageing.Low uniqueness index of the gut microbiome and high representation of Bacteroides are independently associated with mortality in older individuals, while the centenarian microbiome is characterized by high abundance of Lactobacilli and Bifidobacteria . Frailty syndrome, sarcopenia and cognitive decline are associated with reduced faecal microbiota biodiversity, reduced abundance of bacteria able to synthetize short-chain fatty acids (SCFA), including Faecalibacterium prausnitzii , and reduced faecal butyrate levels. Dietary intervention, especially involving Mediterranean diet, and exercise training seem to be associated with improved biodiversity of the microbiota, increased capacity of SCFA synthesis and, probably, protection against the onset of frailty and cognitive decline.The gut microbiota biodiversity and composition may reflect the different ageing trajectory, but further research is needed to understand potential independent and combined effects of environmental and lifestyle factors in older adults, especially from a clinical point of view. 

Intestinal microbiome in normal ageing, frailty and cognition decline

Purpose of review The intestinal microbiome modulates the risk of several age-related chronic diseases and syndromes, including frailty and neurodegenerative diseases. Herein we provided an update on the influence of gut microbiota on physical and cognitive performance in older age and suggest microbiota-targeted interventions for healthy ageing. Recent findings Low uniqueness index of the gut microbiome and high representation of Bacteroides are independently associated with mortality in older individuals, while the centenarian microbiome is characterized by high abundance of Lactobacilli and Bifidobacteria. Frailty syndrome, sarcopenia and cognitive decline are associated with reduced faecal microbiota biodiversity, reduced abundance of bacteria able to synthetize short-chain fatty acids (SCFA), including Faecalibacterium prausnitzii, and reduced faecal butyrate levels. Dietary intervention, especially involving Mediterranean diet, and exercise training seem to be associated with improved biodiversity of the microbiota, increased capacity of SCFA synthesis and, probably, protection against the onset of frailty and cognitive decline. Summary The gut microbiota biodiversity and composition may reflect the different ageing trajectory, but further research is needed to understand potential independent and combined effects of environmental and lifestyle factors in older adults, especially from a clinical point of view.

Abstract The gut microbes play important roles in human longevity and the gut microbiota profile of centenarians shows some unique features from young adults. Nowadays, most microbial studies on longevity are commonly based on metagenomic sequencing which may lose information about the functional microbes with extremely low abundance. Here, we combined in-depth metagenomic sequencing and large-scale culturomics to reveal the unique gut microbial structure of a Chinese longevity population, and to explore the possible relationship between intestinal microbes and longevity. Twenty-five healthy Hainan natives were enrolled in the study, including 12 centenarians and 13 senior neighbors. An average of 51.1 Gb raw sequencing data were obtained from individual fecal sample. We assembled 1778 non-redundant metagenomic assembled genomes (MAGs), 33.46% of which cannot be classified into known species. Comparison with the ordinary people in Hainan province, the longevous cohort displayed significantly decreased abundance of butyrate-producing bacteria and largely increased proportion of Escherichia coli , Desulfovibrio piger and Methanobrevibacter smithii . These species showed a constant change with aging. We also isolated 8,030 strains from these samples by large-scale culturomics, most of which belonged to 203 known species as identified by MALDI-TOF. Surprisingly, only 42.17% of the isolated species were also detected by metagenomics, indicating obvious complementarity between these two approaches. Combination of two complement methods, in-depth metagenomic sequencing and culturomics, provides deeper insights into the longevity-related gut microbiota. The uniquely enriched gut microbes in Hainan extreme decades population may help to promote health and longevity. 

/pdf/deep-insights-into-the-gut-microbial-community-of-extreme-3aejdznr.pdf

Deep insights into the gut microbial community of extreme longevity in south Chinese centenarians by ultra-deep metagenomics and large-scale culturomics

We previously confirmed that a strain of Lactobacillus oris isolated from the fecal samples of healthy Hainan centenarian having potent lipid-lowering ability in HepG2 cells; and this study was to investigate the effect of the stain on non-alcoholic fatty liver in mice in vivio. The Lactobacillus oris strain isolated from Hainan centenarian fecal samples were frozen stored in our laboratory. Thirty ob/ob mice (10 in each group) were orally gavaged with Lactobacillus oris (Lactobacillus, 5 × 109 cfu), mixed probiotics (Mixed, 5 × 109 cfu, a mixture with known lipid-lowering ability), or culture medium (Control) respectively. Lactobacillus oris isolated from fecal samples of Hainan centenarians showed significantly in vivo lipid lowering ability compared with the controls, and the ability was comparable with mixed probiotics strains in mice The possible mechanisms of lipid-lowering of probiotics and Lactobacillus oris may be associated with HMGR inhibition to suppress the synthesis of endogenous cholesterol; bile acids reabsorption, and intestinal FXR-FGF15 signaling pathways promoting the cholesterol conversion into bile acids secretion. 

Lactobacillus oris improves non-alcoholic fatty liver in mice and inhibits endogenous cholesterol biosynthesis

Author Correction: Deep insights into the gut microbial community of extreme longevity in south Chinese centenarians by ultra-deep metagenomics and large-scale culturomics

/pdf/deep-insights-into-the-gut-microbial-community-of-extreme-35aoqajh.pdf

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Deep insights into the gut microbial community of extreme longevity in south Chinese centenarians by ultra-deep metagenomics and large-scale culturomics

Lactobacillus oris improves non-alcoholic fatty liver in mice and inhibits endogenous cholesterol biosynthesis

Author Correction: Deep insights into the gut microbial community of extreme longevity in south Chinese centenarians by ultra-deep metagenomics and large-scale culturomics

Deep insights into the gut microbial community of extreme longevity in south Chinese centenarians by ultra-deep metagenomics and large-scale culturomics