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Updated: Jun 24, 2025
An In Vitro Batch-culture Model to Estimate the Effects of Interventional Regimens on Human Fecal Microbiota
Published on: July 31, 2019
Exploring causal effects of gut microbiota and metabolites on body fat percentage using two-sample Mendelian
Xiaojun Wang1, Chunrong Lu1, Xiang Li1,2
1AIage Life Science Corporation Ltd., Guangxi Free Trade Zone Aisheng Biotechnology Corporation Ltd., Nanning, China.
Aim:
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.
Materials And Methods:
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.
Results:
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 × 10-3], f_Bifidobacteriaceae (β = -0.05; 95% CI: -0.07 to -0.07; FDR = 2.76 × 10-3), p_Actinobacteria (β = -0.06; 95% CI: -0.09 to -0.03; FDR = 6.36 × 10-3), c_Actinobacteria (β = -0.05; 95% CI: -0.08 to -0.02; FDR = 1.06 × 10-2), g_Bifidobacterium (β = -0.05; 95% CI: -0.07 to -0.02; FDR = 1.85 × 10-2), g_Ruminiclostridium9 (β = -0.03; 95% CI: -0.06 to -0.01; FDR = 4.81 × 10-2) were negatively associated with BFP. G_Olsenella (β = 0.02; 95% CI: 0.01-0.03; FDR = 2.16 × 10-2) 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 × 10-6) was associated with BFP.
Conclusions:
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.
