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Biological Aging and the Human Gut Microbiota

机译:生物老化和人体肠道微生物

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摘要

The human gastrointestinal microbiota plays a key homeostatic role in normal functioning of physiologic processes commonly undermined by aging. We used a previously validated 34-item frailty index (FI 34) to identify changes in gut microbiota community structure associated with biological age of community-dwelling adults. Stool 16S rRNA cDNA libraries from 85 subjects ranging in age (43-79) and FI 34 score (0-0.365) were deep sequenced, denoised, and clustered using DADA2. Subject biological age but not chronological age correlated with a decrease in stool microbial diversity. Specific microbial genera were differentially abundant in the lower, middle, and upper 33rd percentiles of biological age. Using Sparse Inverse Covariance Estimation for Ecological Association and Statistical Inference (SPIEC-EASI) and Weighted Gene Co-Expression Network Analysis (WGCNA), we identified modules of coabundant microbial genera that distinguished biological from chronological aging. A biological age-associated module composed of Eggerthella, Ruminococcus, and Coprobacillus genera was robust to correction for subject age, sex, body mass index, antibiotic usage, and other confounders. Subject FI 34 score positively correlated with the abundance of this module, which exhibited a distinct inferred metagenome as predicted by Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt). We conclude that increasing biological age in community-dwelling adults is associated with gastrointestinal dysbiosis.
机译:人体胃肠道微生物群在通常因衰老而受损的生理过程的正常功能中起着关键的稳态作用。我们使用之前验证的34项脆弱指数(FI 34)来确定与社区居住成年人的生物年龄相关的肠道微生物群落结构的变化。使用DADA2对85名年龄(43-79岁)和FI 34评分(0-0.365)的受试者粪便16S rRNA cDNA文库进行深度测序、去噪和聚类。受试者的生物年龄与粪便微生物多样性下降相关,但与时间无关。特定的微生物属在生物年龄的第33百分位下限、中间和上限存在差异。利用稀疏逆协方差估计生态关联和统计推断(SPIEC-EASI)和加权基因共表达网络分析(WGCNA),我们确定了区分生物老化和年代老化的共生微生物属模块。由埃格特氏菌属、瘤胃球菌属和粪杆菌属组成的生物年龄相关模块对受试者年龄、性别、体重指数、抗生素使用和其他混杂因素的校正具有鲁棒性。受试者FI 34得分与该模块的丰度呈正相关,该模块显示出一个独特的推断元基因组,正如通过重建未观察状态(PICRUSt)对群落进行系统发育研究所预测的那样。我们得出结论,居住在社区的成年人生物年龄的增加与胃肠道失调有关。

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