Table_3_Gut Microbiota Composition and Metabolic Potential of Long-Living People in China.pdf

Individuals with naturally long-life spans have been extensively studied to gain a greater understanding of what factors contribute to their overall health and ability to delay or avoid certain diseases. Our previous work showed that gut microbiota can be a new avenue in healthy aging studies. In the present study, a total of 86 Chinese individuals were assigned into three groups: the long-living group (90 + years old; n = 28), the elderly group (65–75 years old; n = 31), and the young group (24–48 years old; n = 27). These groups were used to explore the composition and functional genes in the microbiota community by using the metagenomic sequencing method. We found that long-living individuals maintained high diversity in gene composition and functional profiles. Furthermore, their microbiota displays less inter-individual variation than that of elderly adults. In the taxonomic composition, it was shown that long-living people contained more short-chain fatty acid (SCFA)-producing bacteria and a decrease in certain pathogenic bacteria. Functional analysis also showed that the long-living people were enriched in metabolism metabolites methanol, trimethylamine (TMA), and CO2 to methane, and lysine biosynthesis, but the genes related to riboflavin (vitamin B2) metabolism and tryptophan biosynthesis were significantly reduced in long-living individuals. Further, we found that long-living people with enriched SCFA- and lactic-producing bacteria and related genes, highly centered on producing key lactic acid genes (ldhA) and the genes of lysine that are metabolized to the butyrate pathway. In addition, we compared the gut microbiota signatures of longevity in different regions and found that the composition of the gut microbiota of the long-lived Chinese and Italian people was quite different, but both groups were enriched in genes related to methane production and glucose metabolism. In terms of SCFA metabolism, the Chinese long-living people were enriched with bacteria and genes related to butyric acid production, while the Italian long-living people were enriched with more acetic acid-related genes. These findings suggest that the gut microbiota of Chinese long-living individuals include more SCFA-producing bacteria and genes, metabolizes methanol, TMA, and CO2, and contains fewer pathogenic bacteria, thereby potentially contributing to the healthy aging of humans.

对具有自然长寿的个体进行了广泛的研究，旨在深入理解何种因素有助于其整体健康并延缓或避免某些疾病。本研究的前期工作揭示了肠道微生物群在健康老龄化研究中的新路径。在本研究中，共选取了86名中国个体，将其分为三组：长寿组（90岁以上；n=28）、老年组（65-75岁；n=31）和青年组（24-48岁；n=27）。通过使用宏基因组测序技术，这些组别被用来探究微生物群落的组成和功能基因。研究发现，长寿个体在基因组成和功能特征上保持着较高的多样性。此外，他们的微生物群在个体间的变异性方面相较于老年成人更低。在分类组成方面，长寿人群含有更多产短链脂肪酸（SCFA）的细菌，且某些致病菌含量有所下降。功能分析亦表明，长寿人群在代谢代谢物甲醇、三甲胺（TMA）和二氧化碳至甲烷的代谢，以及赖氨酸生物合成方面富集，而与核黄素（维生素B2）代谢和色氨酸生物合成相关的基因在长寿个体中显著减少。进一步研究发现，长寿个体中富含产SCFA和乳酸的细菌及其相关基因，这些基因高度集中于产生关键乳酸基因（ldhA）和转化为丁酸途径的赖氨酸基因。此外，我们还比较了不同地区长寿个体的肠道微生物群特征，发现长寿的中国人和意大利人的肠道微生物群组成存在显著差异，但两组人群均富集了与甲烷产生和葡萄糖代谢相关的基因。在SCFA代谢方面，中国长寿人群富含与丁酸生产相关的细菌和基因，而意大利长寿人群则富含更多与乙酸相关的基因。这些发现表明，中国长寿个体的肠道微生物群包括更多产SCFA的细菌和基因，能代谢甲醇、TMA和CO2，且含有较少的致病菌，从而可能有助于人类的健康老龄化。