Exploring causal effects of gut microbiota and metabolites on body fat percentage using two-sample Mendelian randomization.

Autor: Wang X; AIage Life Science Corporation Ltd., Guangxi Free Trade Zone Aisheng Biotechnology Corporation Ltd., Nanning, China., Lu C; AIage Life Science Corporation Ltd., Guangxi Free Trade Zone Aisheng Biotechnology Corporation Ltd., Nanning, China., Li X; AIage Life Science Corporation Ltd., Guangxi Free Trade Zone Aisheng Biotechnology Corporation Ltd., Nanning, China.; Medical College, Guangxi University, Nanning, China., Ye P; AIage Life Science Corporation Ltd., Guangxi Free Trade Zone Aisheng Biotechnology Corporation Ltd., Nanning, China., Ma J; AIage Life Science Corporation Ltd., Guangxi Free Trade Zone Aisheng Biotechnology Corporation Ltd., Nanning, China., Chen X; AIage Life Science Corporation Ltd., Guangxi Free Trade Zone Aisheng Biotechnology Corporation Ltd., Nanning, China.
Jazyk: angličtina
Zdroj: Diabetes, obesity & metabolism [Diabetes Obes Metab] 2024 Sep; Vol. 26 (9), pp. 3541-3551. Date of Electronic Publication: 2024 Jun 03.
DOI: 10.1111/dom.15692
Abstrakt: 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.
(© 2024 John Wiley & Sons Ltd.)
Databáze: MEDLINE
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