Table_5_Gut Microbiome Signature Are Correlated With Bone Mineral Density Alterations in the Chinese Elders.docx

ObjectiveOsteoporosis (OP), clinically featured with a low bone mineral density (BMD) and high risk of bone fracture, has become a major risk factor of disability and death in the elders, especially in postmenopausal women. The gut microbiome (GM) is thought to be implicated in bone metabolism. Herein, we clarified the composition signature and gene functional profile of GM in older people with normal and low BMD.Design and MethodsA total of 455 participants underwent the BMD measurement and biochemical detection. GM analysis was further performed on 113 cases of postmenopausal women and men aged over 50, including both 16S rRNA and metagenomic sequencing.ResultsGenerally, the BMD value was significantly lower in the older age groups, especially in the postmenopausal women. Consistently, we observed obvious vitamin D deficiency or insufficiency in females (compared to the male, P < 0.0001). The results from 16S rRNA sequencing revealed higher numbers of OTUs and diversity indexes in females than in males. The abundance in composition of Firmicutes and Clostridiales were correlated with the BMD values in females. LEfSe analysis discovered several enriched bacteria taxons in OP and normal control (NC) subgroups. A positive correlation between the number of genes and BMD values was observed in females based on metagenomic sequencing analysis. Furthermore, we identified the connecting modules among the GM composition – gene functional signature – BMD value/T score in both females and males.ConclusionsThis study provides evidences upon which to understand the mechanisms of the effects of GM on bone health, consequently revealing the physiology status and potential diagnostic/therapeutic targets based on GM for OP and postmenopausal osteoporosis (PMOP). Besides, the status of vitamin D deficiency or insufficiency need to be concerned and improved in the Chinese people.

骨质疏松症（OP），临床表现为低骨矿物质密度（BMD）和高骨骨折风险，已成为老年人致残和死亡的主要风险因素，尤其是在绝经后妇女中。据认为，肠道微生物组（GM）与骨代谢有关。本研究旨在阐明老年人正常和低BMD状态下GM的组成特征和基因功能图谱。研究设计与方法：共有455名参与者接受了BMD测量和生化检测。对113例绝经后妇女和50岁以上男性的GM进行了进一步分析，包括16S rRNA和宏基因组测序。结果：总体而言，随着年龄的增长，BMD值显著降低，特别是在绝经后妇女中。一致地，我们观察到女性（与男性相比，P < 0.0001）存在明显的维生素D缺乏或不足。16S rRNA测序结果显示，女性中的操作分类单元（OTUs）和多样性指数高于男性。厚壁菌门和拟杆菌门在女性中的组成丰度与BMD值相关。LEfSe分析在OP和正常对照组（NC）亚组中发现了几个富集的细菌分类群。基于宏基因组测序分析，观察到女性基因数量与BMD值之间存在正相关。此外，我们在男性和女性中识别了GM组成、基因功能特征与BMD值/T评分之间的连接模块。结论：本研究为理解GM对骨健康影响的机制提供了证据，从而揭示了基于GM的骨质疏松症（OP）和绝经后骨质疏松症（PMOP）的生理状态和潜在的诊断/治疗靶点。此外，需要关注并改善中国人群维生素D缺乏或不足的状态。