Genus_Ruminococcus and order_Burkholderiales affect osteoporosis by regulating the microbiota-gut-bone axis

Ning Li, Haiyang Wang, Huan Pei, Yueying Wu, Lei Li, Yu Ren, Si Wang, Yuan Ma, Miao Luo, Jiali Yuan, Lvyu Li, Dongdong Qin
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Abstract

This study aimed to clarify the relationship between the gut microbiota and osteoporosis combining Mendelian randomization (MR) analysis with animal experiments.We conducted an analysis on the relationship between differential bacteria and osteoporosis using open-access genome-wide association study (GWAS) data on gut microbe and osteoporosis obtained from public databases. The analysis was performed using two-sample MR analysis, and the causal relationship was examined through inverse variance weighting (IVW), MR Egger, weighted median, and weighted mode methods. Bilateral oophorectomy was employed to replicate the mouse osteoporosis model, which was assessed by micro computed tomography (CT), pathological tests, and bone transformation indexes. Additionally, 16S rDNA sequencing was conducted on fecal samples, while SIgA and indexes of IL-6, IL-1β, and TNF-α inflammatory factors were examined in colon samples. Through immunofluorescence and histopathology, expression levels of tight junction proteins, such as claudin-1, ZO-1, and occludin, were assessed, and conduct correlation analysis on differential bacteria and related environmental factors were performed.A positive correlation was observed between g_Ruminococcus1 and the risk of osteoporosis, while O_Burkholderiales showed a negative correlation with the risk of osteoporosis. Furthermore, there was no evidence of heterogeneity or pleiotropy. The successful replication of the mouse osteoporosis model was assessed, and it was found that the abundance of the O_Burkholderiales was significantly reduced, while the abundance of g_Ruminococcus was significantly increased in the ovariectomized (OVX)-mice. The intestinal SIgA level of OVX mice decreased, the expression level of inflammatory factors increased, barrier damage occurred, and the content of LPS in the colon and serum significantly increased. The abundance level of O_Burkholderiales is strongly positively correlated with bone formation factors, gut barrier indicators, bone density, bone volume fraction, and trabecular bone quantity, whereas it was strongly negatively correlated with bone resorption factors and intestinal inflammatory factors, The abundance level of g_Ruminococcus shows a strong negative correlation with bone formation factors, gut barrier indicators, and bone volume fraction, and a strong positive correlation with bone resorption factors and intestinal inflammatory factors.O_Burkholderiales and g_Ruminococcus may regulate the development of osteoporosis through the microbiota-gut-bone axis.
反刍球菌属和糠虾纲通过调节微生物群-肠-骨轴来影响骨质疏松症
本研究旨在结合孟德尔随机分析法(MR)和动物实验,阐明肠道微生物群与骨质疏松症之间的关系。我们利用从公共数据库中获取的肠道微生物与骨质疏松症的全基因组关联研究(GWAS)数据,对不同细菌与骨质疏松症之间的关系进行了分析。分析采用双样本 MR 分析法,并通过反方差加权法(IVW)、MR Egger 法、加权中位数法和加权模式法对因果关系进行了检验。采用双侧输卵管切除术复制小鼠骨质疏松症模型,并通过显微计算机断层扫描(CT)、病理测试和骨转换指数进行评估。此外,还对粪便样本进行了 16S rDNA 测序,并检测了结肠样本中的 SIgA 以及 IL-6、IL-1β 和 TNF-α 炎症因子的指数。通过免疫荧光和组织病理学,评估了紧密连接蛋白(如 claudin-1、ZO-1 和 occludin)的表达水平,并对不同细菌和相关环境因素进行了相关性分析。此外,没有证据表明存在异质性或多义性。对小鼠骨质疏松症模型的成功复制进行了评估,发现在卵巢切除(OVX)小鼠中,O_伯克霍尔德氏菌的丰度显著降低,而g_反刍球菌的丰度显著增加。卵巢切除小鼠肠道 SIgA 水平下降,炎症因子表达水平升高,屏障受损,结肠和血清中 LPS 含量明显升高。O_Burkholderiales 的丰度水平与骨形成因子、肠道屏障指标、骨密度、骨体积分数和骨小梁数量呈强正相关,而与骨吸收因子和肠道炎症因子呈强负相关;g_Ruminococcus 的丰度水平与骨形成因子、肠道屏障指标和骨体积分数呈强负相关,而与骨吸收因子和肠道炎症因子呈强正相关。O_Burkholderiales 和 g_Ruminococcus 可能通过微生物群-肠-骨轴来调节骨质疏松症的发展。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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