Exploring causal effects of gut microbiota and metabolites on body fat percentage using two-sample Mendelian randomization.
Diabetes Obes Metab
; 26(9): 3541-3551, 2024 Sep.
Article
em En
| MEDLINE
| ID: mdl-38828839
ABSTRACT
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 ANDMETHODS:
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 [ß = -0.05; 95% confidence interval (CI) -0.07 to -0.03; false discovery rate (FDR) = 2.76 × 10-3], f_Bifidobacteriaceae (ß = -0.05; 95% CI -0.07 to -0.07; FDR = 2.76 × 10-3), p_Actinobacteria (ß = -0.06; 95% CI -0.09 to -0.03; FDR = 6.36 × 10-3), c_Actinobacteria (ß = -0.05; 95% CI -0.08 to -0.02; FDR = 1.06 × 10-2), g_Bifidobacterium (ß = -0.05; 95% CI -0.07 to -0.02; FDR = 1.85 × 10-2), g_Ruminiclostridium9 (ß = -0.03; 95% CI -0.06 to -0.01; FDR = 4.81 × 10-2) were negatively associated with BFP. G_Olsenella (ß = 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 (ß = 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.Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Polimorfismo de Nucleotídeo Único
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Estudo de Associação Genômica Ampla
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Análise da Randomização Mendeliana
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Microbioma Gastrointestinal
Limite:
Female
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Humans
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Male
Idioma:
En
Revista:
Diabetes Obes Metab
Assunto da revista:
ENDOCRINOLOGIA
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METABOLISMO
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China