Table_1_Gut Microbiota Composition and Metabolic Potential of Long-Living People in China.xlsx

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.

对长寿个体进行了广泛的研究，以深入探究影响其整体健康及延缓或避免特定疾病发生的因素。既往研究揭示了肠道菌群在健康老龄化研究中的新途径。在本研究中，共纳入86名中国个体，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）。通过宏基因组测序方法，对这三组人群的肠道菌群组成和功能基因进行分析。研究发现，长寿个体在基因组成和功能特征上保持了较高的多样性。此外，与老年成人相比，长寿个体的肠道菌群个体间差异较小。在分类组成方面，长寿人群含有更多短链脂肪酸（SCFA）产生菌，且某些致病菌数量减少。功能分析亦表明，长寿人群在甲醇、三甲胺（TMA）和二氧化碳转化为甲烷的代谢产物中富集，并在赖氨酸生物合成方面有所增强，但与核黄素（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降低。进一步研究还发现，富含SCFA和乳酸产生菌及其相关基因的长寿个体，高度集中于产生关键乳酸酸基因（ldhA）和赖氨酸代谢为丁酸途径的基因。此外，我们比较了不同地区长寿人群的肠道菌群特征，发现长寿的中国人和意大利人的肠道菌群组成存在显著差异，但两组人群均富含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产生相关的细菌和基因，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菌群包含更多SCFA产生菌和基因，能够代谢甲醇、TMA和二氧化碳，并含有较少的致病菌，从而可能对人类的健康老龄化产生积极作用。