Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, Jiangsu, PR China; Center for Genetic Epidemiology and Genomics, School of Public Health, Medical College of Soochow University, Jiangsu, PR China.
Department of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, Jiangsu, PR China; Laboratory of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, Jiangsu, PR China.
Bone. 2021 Feb;143:115652. doi: 10.1016/j.bone.2020.115652. Epub 2020 Sep 21.
Recent studies have demonstrated the important role played by gut microbiota in regulating bone development, but the evidence of such causal relationship is still sparse in human population. The aim of this study is to assess the causal relationship from gut microbiota to bone development and to identify specific causal bacteria taxa via a Mendelian randomization (MR) approach. A genome-wide association study (GWAS) summary statistic based two-sample MR analysis was performed. Summary statistics of microbiome GWAS (MGWAS) in 1126 twin pairs of the TwinsUK study was used as discovery sample, and the MGWAS in 984 Dutch participants from the LifeLines-DEEP cohort was used as replication sample. Estimated heel bone mineral density (eBMD) GWAS in 426,824 participants from the UK biobank (UKB) cohort was used as outcome. Bacteria were grouped into taxa features at both order and family levels. In the discovery sample, a total of 25 bacteria features including 9 orders and 16 families were analyzed. Fourteen features (5 orders + 9 families) were nominally significant, including 5 orders (Bacteroidales, Clostridiales, Lactobacillales, Pasteurellales and Verrucomicrobiales) and 9 families (Bacteroidaceae, Clostridiaceae, Lachnospiraceae, Mogibacteriaceae, Pasteurellaceae, Porphyromonadaceae, Streptococcaceae, Verrucomicrobiaceae and Veillonellaceae). One order Clostridiales and its child taxon, family Lachnospiraceae, were successfully replicated in the replication sample (Clostridiales P = 3.32 × 10P = 7.29 × 10; Lachnospiraceae P = 0.03 P = 7.29 × 10). Our findings provided evidence of causal relationship from microbiota to bone development, as well as identified specific bacteria taxa that regulated bone mass variation, thus providing new insights into the microbiota mediated bone development mechanism.
最近的研究表明，肠道微生物群在调节骨骼发育中起着重要作用，但在人类群体中，这种因果关系的证据仍然很少。本研究旨在通过孟德尔随机化（MR）方法评估肠道微生物群对骨骼发育的因果关系，并确定特定的因果细菌分类群。进行了基于全基因组关联研究（GWAS）汇总统计的两样本 MR 分析。使用 TwinsUK 研究中 1126 对双胞胎的微生物组 GWAS（MGWAS）汇总统计作为发现样本，使用来自 LifeLines-DEEP 队列的 984 名荷兰参与者的 MGWAS 作为复制样本。使用来自 UK Biobank（UKB）队列的 426824 名参与者的估计脚跟骨骨密度（eBMD）GWAS 作为结果。细菌被分为分类群特征，包括在订单和家庭水平。在发现样本中，总共分析了 25 个细菌特征，包括 9 个订单和 16 个科。14 个特征（5 个订单+9 个科）具有名义显著性，包括 5 个订单（拟杆菌目、梭菌目、乳杆菌目、巴氏杆菌目和疣微菌目）和 9 个科（拟杆菌科、梭菌科、lachnospiraceae、莫吉比科、巴氏杆菌科、卟啉单胞菌科、链球菌科、疣微菌科和韦荣球菌科）。一个订单梭菌目及其子分类群lachnospiraceae，在复制样本中成功复制（梭菌目 P=3.32×10 P=7.29×10；lachnospiraceae P=0.03 P=7.29×10）。我们的研究结果提供了肠道微生物群与骨骼发育之间因果关系的证据，并确定了调节骨量变化的特定细菌分类群，从而为微生物群介导的骨骼发育机制提供了新的见解。
