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Background <p>Gut microbiota (GM) plays a critical role in maintaining human health and modulating the pathogenesis of various diseases. This study aimed to investigate the causal relationship between gut microbiota and childhood obesity using Mendelian randomization.</p> Methods <p>In accordance with preset thresholds, independent genetic loci significantly related to the relative abundance of GM were extracted as instrumental variables using GM genome-wide association study (GWAS) data from the MiBioGen database and childhood obesity GWAS data from the IEU Open GWAS database. Inverse variance weighting was used to examine the causal relationship between GM and childhood obesity.</p> Results <p>An increase in <i>Akkermansia</i> and <i>Butyricimonas</i> abundance can reduce the risk of obesity in children <i>(</i>OR = 0.476, 95% CI: 0.311–0.726, <i>P</i> = 0.001; OR = 0.682, 95% CI: 0.471–0.990, <i>P</i> = 0.044). <i>Ruminiclostridium9</i> abundance increased the risk of childhood obesity (OR = 2.051, 95% CI: 1.069–3.932, <i>P</i> = 0.031).</p> Conclusion <p>Beneficial GM members <i>Akkermansia</i> and <i>Butyricimonas</i> were positively associated with reduced obesity risk in children. <i>Ruminiclostridium 9</i> was identified as a potential risk factor for childhood obesity. This study provides genetic evidence supporting a potential causal relationship between GM composition and childhood obesity, offering valuable insights for future research and preventive intervention strategies.</p> Impact <p>Gut microbiota (GM) plays a critical role in maintaining human health and modulating the pathogenesis of various diseases. GM-based interventions have emerged as promising therapeutic approaches for childhood obesity. This study aimed to investigate the causal relationship between gut microbiota and childhood obesity using Mendelian randomization methods, thereby providing genetic evidence to support the potential of GM-targeted strategies in the prevention and management of this condition. The findings reinforce prior observational evidence by demonstrating a causal association between specific gut microbial taxa and childhood obesity. These results provide valuable insights that may guide future research and the development of novel therapeutic interventions.</p>

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Genetically mediated causal relationship between gut microbiota composition and childhood obesity

  • 期刊论文

  • 发表日期：

    2026年3月25日

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  • Lei Wang,
  • Ya-hui Xiao,
  • Zhen-jiang Hu,
  • Ping-ping Yin,
  • Ai-lian Chen,
  • Jin-lin Peng

摘要

Background

Gut microbiota (GM) plays a critical role in maintaining human health and modulating the pathogenesis of various diseases. This study aimed to investigate the causal relationship between gut microbiota and childhood obesity using Mendelian randomization.

Methods

In accordance with preset thresholds, independent genetic loci significantly related to the relative abundance of GM were extracted as instrumental variables using GM genome-wide association study (GWAS) data from the MiBioGen database and childhood obesity GWAS data from the IEU Open GWAS database. Inverse variance weighting was used to examine the causal relationship between GM and childhood obesity.

Results

An increase in Akkermansia and Butyricimonas abundance can reduce the risk of obesity in children (OR = 0.476, 95% CI: 0.311–0.726, P = 0.001; OR = 0.682, 95% CI: 0.471–0.990, P = 0.044). Ruminiclostridium9 abundance increased the risk of childhood obesity (OR = 2.051, 95% CI: 1.069–3.932, P = 0.031).

Conclusion

Beneficial GM members Akkermansia and Butyricimonas were positively associated with reduced obesity risk in children. Ruminiclostridium 9 was identified as a potential risk factor for childhood obesity. This study provides genetic evidence supporting a potential causal relationship between GM composition and childhood obesity, offering valuable insights for future research and preventive intervention strategies.

Impact

Gut microbiota (GM) plays a critical role in maintaining human health and modulating the pathogenesis of various diseases. GM-based interventions have emerged as promising therapeutic approaches for childhood obesity. This study aimed to investigate the causal relationship between gut microbiota and childhood obesity using Mendelian randomization methods, thereby providing genetic evidence to support the potential of GM-targeted strategies in the prevention and management of this condition. The findings reinforce prior observational evidence by demonstrating a causal association between specific gut microbial taxa and childhood obesity. These results provide valuable insights that may guide future research and the development of novel therapeutic interventions.