Table_4_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.

对长寿个体进行了广泛研究，以深入探究影响其整体健康及延缓或避免特定疾病因素的构成。前期研究揭示，肠道微生物群可作为健康老龄化研究的新路径。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，对微生物群落的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高度多样性。此外，其微生物群在个体间变异方面低于老年人群。在分类组成上，长寿者体内含有更多产短链脂肪酸（SCFA）的细菌和减少的某些病原菌。功能分析亦显示，长寿者富含甲醇、三甲胺（TMA）、二氧化碳到甲烷的代谢产物以及赖氨酸生物合成，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减少。进一步研究还发现，富含SCFA和乳酸产生细菌及其相关基因的长寿者，高度集中于产关键乳酸基因（ldhA）及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肠道微生物群的特征，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，中国长寿者富含与丁酸产生相关的细菌和基因，而意大利长寿者富含更多与乙酸相关的基因。这些发现表明，中国长寿者的肠道微生物群包括更多SCFA产生细菌和基因，代谢甲醇、TMA和二氧化碳，且含有较少的病原菌，从而可能有助于人类的健康老龄化。