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| 肠道菌群与PTH存在因果关联：来自孟德尔随机化研究的证据 |
| Causal Association Between Gut Microbiota and PTH: Evidence from Mendelian Randomization Studies |
| 投稿时间：2025-08-19 修订日期：2025-09-10 |
| DOI： |
| 中文关键词: 骨质疏松症 肠道菌群 PTH 骨代谢 肠骨轴 孟德尔随机化 因果关系 |
| 英文关键词:Osteoporosis Gut microbiota Parathyroid hormone (PTH) Bone metabolism Gut-bone axis Mendelian randomization Causal relationship |
| 基金项目:国家自然科学基金(81860855)贵州省科技计划:贵州省苗医药全省重点实验室 黔科合平台[2025]018；贵州省中医药、民族医药科学技术研究专项(QZYY-2025-023)。贵州省卫健委科学技术基金课题,项目编号:(gzwkj2025-364)。北京积水潭医院贵州医院院内课题JGYYK[2025]16号 |
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| 中文摘要: |
| 目的:基于双向孟德尔随机化(MR)方法探讨肠道菌群与甲状旁腺激素(PTH)水平之间的潜在因果关系。方法:获取肠道菌群与甲状旁腺激素(PTH)的SNP为工具变量。利用逆方差加权法(IVW)、MR Egger及加权中位数法等进行双向MR分析并评估敏感性。结果:采用逆方差加权法评估工具变量因果效应,发现以下肠道菌群分类单元与血清甲状旁腺激素(PTH)水平呈显著正向关联(P < 0.05): 巴斯德菌科(GCST90016944)及巴斯德菌目(GCST90017105):OR= 1.69(95%CI:1.13–2.53,P = 0.010) Hungatella属(GCST90017017)及Family XIII AD3011组(GCST90017008):OR = 1.57(95% CI 1.09–2.25,P = 0.015) 毛螺菌科NK4A136组(GCST90017024):OR = 1.57(95% CI 1.09–2.25,P = 0.015) 上述结果提示,相关菌群丰度增加与PTH水平升高存在统计学显著的因果效应。反向MR分析提示, PTH水平升高与毛螺菌科NK4A136组(OR=1.052,95%CI:1.001-1.106,P=0.047 )、Anaerotrunccus属(OR=1.049,95%CI:1.020-1.080,P=0.001 )、卟啉单胞菌科(OR=1.037,95%CI:1.009-1.066,P=0.009 )、FamilyXII UCG001属(OR=1.034,95%CI:1.001-1.068,P=0.043 )、Marvinbryantia属(OR=1.035,95%CI:1.001-1.071,P=0.042 )和Ruminococcus torques组(OR=1.028,95%CI:1.000-1.057,P=0.048 )呈正向因果关联；与梭菌科1(OR=0.965,95%CI:0.935-0.995,P=0.023 )和严谨梭菌属1(OR=0.963,95%CI:0.934-0.994,P=0.020 )呈负向因果关联。这些结果表明,PTH水平变化可能通过调节特定肠道菌群丰度来影响宿主健康。结论:本MR分析明确了肠道菌群与PTH的因果关联,为进一步探索肠道菌群对PTH和骨代谢的影响提供了新的视角,并为针对肠道菌群调节PTH提供了新的策略。 |
| 英文摘要: |
| Objective: To investigate bidirectional causal relationships between gut microbiota composition and serum parathyroid hormone (PTH) levels using Mendelian randomization (MR) analysis.Methods: Genome-wide association study (GWAS)-derived single nucleotide polymorphisms (SNPs) served as instrumental variables. Bidirectional MR analyses were performed using inverse variance weighted (IVW), MR-Egger, and weighted median methods, complemented by sensitivity assessments.Results: Forward MR analysis using IVW demonstrated significant positive associations (P < 0.05) between PTH levels and five gut microbiota taxa:Pasteurellaceae(GCST90016944) andPasteurellales(GCST90017105): Odds Ratio (OR) = 1.69 (95% Confidence Interval [CI]: 1.13–2.53, P = 0.010)；Hungatellagenus (GCST90017017) and Family XIII AD3011 group (GCST90017008): OR = 1.57 (95% CI: 1.09–2.25, P = 0.015)；LachnospiraceaeNK4A136 group (GCST90017024): OR = 1.57 (95% CI: 1.09–2.25, P = 0.015。These findings indicate statistically significant causal effects of increased microbial abundance on elevated PTH levels. Conversely, reverse MR analysis revealed that elevated PTH levels were positively associated with:LachnospiraceaeNK4A136 group (OR = 1.052, 95% CI: 1.001–1.106, P = 0.047)；Anaerotruncusgenus (OR = 1.049, 95% CI: 1.020–1.080, P = 0.001)；Porphyromonadaceae(OR = 1.037, 95% CI: 1.009–1.066, P = 0.009)；Family XII UCG001 genus (OR = 1.034, 95% CI: 1.001–1.068, P = 0.043)；Marvinbryantiagenus (OR = 1.035, 95% CI: 1.001–1.071, P = 0.042)；Ruminococcus torquesgroup (OR = 1.028, 95% CI: 1.000–1.057, P = 0.048。Negative associations were observed with:Clostridiaceae1 (OR = 0.965, 95% CI: 0.935–0.995, P = 0.023)；Clostridiumsensu stricto 1 (OR = 0.963, 95% CI: 0.934–0.994, P = 0.020).Conclusion: This MR study establishes bidirectional causal links between gut microbiota and PTH levels, providing genetic evidence for microbiota-mediated regulation of PTH metabolism. These results offer novel insights into gut-bone axis interactions and suggest potential microbiota-targeted strategies for modulating PTH and bone health. |
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