Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, China.
Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, Hangzhou, China.
BMC Med. 2022 May 19;20(1):171. doi: 10.1186/s12916-022-02376-3.
The temporal relationship between adiposity and gut microbiota was unexplored. Whether some gut microbes lie in the pathways from adiposity to insulin resistance is less clear. Our study aims to reveal the temporal relationship between adiposity and gut microbiota and investigate whether gut microbiota may mediate the association of adiposity with insulin resistance in a longitudinal human cohort study.
We obtained repeated-measured gut shotgun metagenomic and anthropometric data from 426 Chinese participants over ~3 years of follow-up. Cross-lagged path analysis was used to examine the temporal relationship between BMI and gut microbial features. The associations between the gut microbes and insulin resistance-related phenotypes were examined using a linear mixed-effect model. We examined the mediation effect of gut microbes on the association between adiposity and insulin resistance-related phenotypes. Replication was performed in the HMP cohort.
Baseline BMI was prospectively associated with levels of ten gut microbial species. Among them, results of four species (Adlercreutzia equolifaciens, Parabacteroides unclassified, Lachnospiraceae bacterium 3 1 57FAA CT1, Lachnospiraceae bacterium 7 1 58FAA) were replicated in the independent HMP cohort. Lachnospiraceae bacterium 3 1 57FAA CT1 was inversely associated with HOMA-IR and fasting insulin. Lachnospiraceae bacterium 3 1 57FAA CT1 mediated the association of overweight/obesity with HOMA-IR (FDR<0.05). Furthermore, Lachnospiraceae bacterium 3 1 57FAA CT1 was positively associated with the butyrate-producing pathway PWY-5022 (p < 0.001).
Our study identified one potentially beneficial microbe Lachnospiraceae bacterium 3 1 57FAA CT1, which might mediate the effect of adiposity on insulin resistance. The identified microbes are helpful for the discovery of novel therapeutic targets, as to mitigate the impact of adiposity on insulin resistance.
肥胖与肠道微生物群之间的时间关系尚未得到探索。一些肠道微生物是否存在于肥胖导致胰岛素抵抗的途径中尚不清楚。我们的研究旨在揭示肥胖与肠道微生物群之间的时间关系，并在一项纵向人类队列研究中调查肠道微生物群是否可能介导肥胖与胰岛素抵抗之间的关联。
我们从 426 名中国参与者中获得了为期约 3 年的重复测量肠道 shotgun 宏基因组和人体测量数据。交叉滞后路径分析用于检查 BMI 与肠道微生物特征之间的时间关系。使用线性混合效应模型检查肠道微生物与胰岛素抵抗相关表型之间的关联。我们检查了肠道微生物对肥胖与胰岛素抵抗相关表型之间关联的中介效应。在 HMP 队列中进行了复制。
基线 BMI 与十种肠道微生物物种的水平呈前瞻性相关。其中，四种物种（产琥珀酸阿克曼氏菌、拟杆菌属未分类、Lachnospiraceae 细菌 3 1 57FAA CT1、Lachnospiraceae 细菌 7 1 58FAA）的结果在独立的 HMP 队列中得到了复制。Lachnospiraceae 细菌 3 1 57FAA CT1 与 HOMA-IR 和空腹胰岛素呈负相关。Lachnospiraceae 细菌 3 1 57FAA CT1 介导超重/肥胖与 HOMA-IR 的关联（FDR<0.05）。此外，Lachnospiraceae 细菌 3 1 57FAA CT1 与丁酸产生途径 PWY-5022 呈正相关（p<0.001）。
我们的研究确定了一种潜在有益的微生物 Lachnospiraceae 细菌 3 1 57FAA CT1，它可能介导肥胖对胰岛素抵抗的影响。所鉴定的微生物有助于发现新的治疗靶点，以减轻肥胖对胰岛素抵抗的影响。
