AIage Life Science Corporation Ltd., Guangxi Free Trade Zone Aisheng Biotechnology Corporation Ltd., Nanning, China.
Medical College, Guangxi University, Nanning, China.
Diabetes Obes Metab. 2024 Sep;26(9):3541-3551. doi: 10.1111/dom.15692. Epub 2024 Jun 3.
The relationship between the gut microbiota, metabolites and body fat percentage (BFP) remains unexplored. We systematically assessed the causal relationships between gut microbiota, metabolites and BFP using Mendelian randomization analysis.
Single nucleotide polymorphisms associated with gut microbiota, blood metabolites and BFP were screened via a genome-wide association study enrolling individuals of European descent. Summary data from genome-wide association studies were extracted from the MiBioGen consortium and the UK Biobank. The inverse variance-weighted model was the primary method used to estimate these causal relationships. Sensitivity analyses were performed using pleiotropy, Mendelian randomization-Egger regression, heterogeneity tests and leave-one-out tests.
In the aspect of phyla, classes, orders, families and genera, we observed that o_Bifidobacteriales [β = -0.05; 95% confidence interval (CI): -0.07 to -0.03; false discovery rate (FDR) = 2.76 × 10], f_Bifidobacteriaceae (β = -0.05; 95% CI: -0.07 to -0.07; FDR = 2.76 × 10), p_Actinobacteria (β = -0.06; 95% CI: -0.09 to -0.03; FDR = 6.36 × 10), c_Actinobacteria (β = -0.05; 95% CI: -0.08 to -0.02; FDR = 1.06 × 10), g_Bifidobacterium (β = -0.05; 95% CI: -0.07 to -0.02; FDR = 1.85 × 10), g_Ruminiclostridium9 (β = -0.03; 95% CI: -0.06 to -0.01; FDR = 4.81 × 10) were negatively associated with BFP. G_Olsenella (β = 0.02; 95% CI: 0.01-0.03; FDR = 2.16 × 10) was positively associated with BFP. Among the gut microbiotas, f_Bifidobacteriales, o_Bifidobacteriales, c_Actinobacteria and p_Actinobacteria were shown to be significantly associated with BFP in the validated dataset. In the aspect of metabolites, we only observed that valine (β = 0.77; 95% CI: 0.5-1.04; FDR = 8.65 × 10) was associated with BFP.
Multiple gut microbiota and metabolites were strongly associated with an increased BFP. Further studies are required to elucidate the mechanisms underlying this putative causality. In addition, BFP, a key indicator of obesity, suggests that obesity-related interventions can be developed from gut microbiota and metabolite perspectives.
肠道微生物群、代谢物与体脂肪百分比（BFP）之间的关系尚未得到探索。我们通过孟德尔随机化分析系统地评估了肠道微生物群、代谢物与 BFP 之间的因果关系。
通过全基因组关联研究筛选与肠道微生物群、血液代谢物和 BFP 相关的单核苷酸多态性，该研究纳入了欧洲血统的个体。来自 MiBioGen 联盟和英国生物库的全基因组关联研究的汇总数据被提取出来。逆方差加权模型是用于估计这些因果关系的主要方法。使用多效性、孟德尔随机化-Egger 回归、异质性检验和单倍型缺失检验进行了敏感性分析。
在门、纲、目、科和属水平上，我们观察到 o_Bifidobacteriales（β=-0.05；95%置信区间（CI）：-0.07 至 -0.03；假发现率（FDR）=2.76×10）、f_Bifidobacteriaceae（β=-0.05；95%CI：-0.07 至 -0.07；FDR=2.76×10）、p_Actinobacteria（β=-0.06；95%CI：-0.09 至 -0.03；FDR=6.36×10）、c_Actinobacteria（β=-0.05；95%CI：-0.08 至 -0.02；FDR=1.06×10）、g_Bifidobacterium（β=-0.05；95%CI：-0.07 至 -0.02；FDR=1.85×10）、g_Ruminiclostridium9（β=-0.03；95%CI：-0.06 至 -0.01；FDR=4.81×10）与 BFP 呈负相关。G_Olsenella（β=0.02；95%CI：0.01-0.03；FDR=2.16×10）与 BFP 呈正相关。在肠道微生物群中，f_Bifidobacteriales、o_Bifidobacteriales、c_Actinobacteria 和 p_Actinobacteria 在验证数据集中与 BFP 显著相关。在代谢物方面，我们只观察到缬氨酸（β=0.77；95%CI：0.5-1.04；FDR=8.65×10）与 BFP 相关。
多种肠道微生物群和代谢物与 BFP 的增加密切相关。需要进一步的研究来阐明这种潜在因果关系的机制。此外，BFP 作为肥胖的关键指标表明，肥胖相关的干预措施可以从肠道微生物群和代谢物的角度来开发。
