Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, Finland.
NPJ Biofilms Microbiomes. 2024 Aug 14;10(1):69. doi: 10.1038/s41522-024-00530-8.
The gut microbiota (GM) can regulate bone mass, but its association with incident fractures is unknown. We used Cox regression models to determine whether the GM composition is associated with incident fractures in the large FINRISK 2002 cohort (n = 7043, 1092 incident fracture cases, median follow-up time 18 years) with information on GM composition and functionality from shotgun metagenome sequencing. Higher alpha diversity was associated with decreased fracture risk (hazard ratio [HR] 0.92 per standard deviation increase in Shannon index, 95% confidence interval 0.87-0.96). For beta diversity, the first principal component was associated with fracture risk (Aitchison distance, HR 0.90, 0.85-0.96). In predefined phyla analyses, we observed that the relative abundance of Proteobacteria was associated with increased fracture risk (HR 1.14, 1.07-1.20), while the relative abundance of Tenericutes was associated with decreased fracture risk (HR 0.90, 0.85-0.96). Explorative sub-analyses within the Proteobacteria phylum showed that higher relative abundance of Gammaproteobacteria was associated with increased fracture risk. Functionality analyses showed that pathways related to amino acid metabolism and lipopolysaccharide biosynthesis associated with fracture risk. The relative abundance of Proteobacteria correlated with pathways for amino acid metabolism, while the relative abundance of Tenericutes correlated with pathways for butyrate synthesis. In conclusion, the overall GM composition was associated with incident fractures. The relative abundance of Proteobacteria, especially Gammaproteobacteria, was associated with increased fracture risk, while the relative abundance of Tenericutes was associated with decreased fracture risk. Functionality analyses demonstrated that pathways known to regulate bone health may underlie these associations.
肠道微生物群(GM)可以调节骨量,但它与骨折事件的关系尚不清楚。我们使用 Cox 回归模型来确定 GM 组成是否与大型 FINRISK 2002 队列中的骨折事件有关(n=7043,1092 例骨折事件,中位随访时间 18 年),该队列提供了 GM 组成和功能的信息,来自 shotgun 宏基因组测序。较高的 alpha 多样性与较低的骨折风险相关(风险比 [HR] 每标准差增加 0.92,95%置信区间为 0.87-0.96)。对于 beta 多样性,第一主成分与骨折风险相关(Aitchison 距离,HR 0.90,0.85-0.96)。在预先定义的门分析中,我们观察到变形菌门的相对丰度与骨折风险增加相关(HR 1.14,1.07-1.20),而厚壁菌门的相对丰度与骨折风险降低相关(HR 0.90,0.85-0.96)。变形菌门内的探索性亚分析表明,γ变形菌纲的相对丰度与骨折风险增加相关。功能分析表明,与氨基酸代谢和脂多糖生物合成相关的途径与骨折风险相关。变形菌门的相对丰度与氨基酸代谢途径相关,而厚壁菌门的相对丰度与丁酸盐合成途径相关。总之,整体 GM 组成与骨折事件相关。变形菌门的相对丰度,特别是γ变形菌纲,与骨折风险增加相关,而厚壁菌门的相对丰度与骨折风险降低相关。功能分析表明,已知调节骨骼健康的途径可能是这些关联的基础。