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<p>The gut microbiota may influence the occurrence and development of colorectal neuroendocrine tumors (CR-NETs), with inflammatory mediators potentially playing an important intermediary role. However, the current research evidence is insufficient to support this view. In this study, we extracted SNP data from different Genome-Wide Association Study (GWAS) summary statistics. Using bidirectional two-sample Mendelian randomization (MR), two-step MR, and multivariable Mendelian randomization (MVMR) methods, we explored the causal relationship between gut microbiota, inflammatory proteins, and CR-NETs. Our study found that five types of gut microbiota (<i>family Acidaminococcaceae</i>,<i> family Porphyromonadaceae</i>,<i> genus Oscillospira</i>,<i> genus Paraprevotella</i>,<i> genus Ruminococcaceae NK4A214 group</i>) and five inflammatory mediators (C-C motif chemokine Ligand 4, C-C motif chemokine Ligand 23, TNF-related apoptosis-inducing ligand, C-X-C motif chemokine Ligand 5, Monocyte chemoattractant protein 2) have a causal relationship with CR-NETs. Additionally, C-C motif chemokine Ligand 23 (CCL23) mediated the causal effect of <i>family Porphyromonadaceae</i> on CR-NETs (with a mediation proportion of 6.3%), while C-C motif chemokine Ligand 4 (CCL4) mediated the causal effect of <i>genus Ruminococcaceae NK4A214 group</i> on CR-NETs (with a mediation proportion of 4.7%). There is a causal relationship between gut microbiota and inflammatory proteins in the development of CR-NETs, with CCL23 and CCL4 possibly playing a mediating role.</p>

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Exploring the causal relationship between gut microbiota, circulating inflammatory proteins, and colorectal neuroendocrine tumors: a Mendelian randomization study

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月26日

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  • Jie Cui,
  • Tie-Jun Wang,
  • Yue-Chen Zhao,
  • Xuan-Peng Zhou

摘要

The gut microbiota may influence the occurrence and development of colorectal neuroendocrine tumors (CR-NETs), with inflammatory mediators potentially playing an important intermediary role. However, the current research evidence is insufficient to support this view. In this study, we extracted SNP data from different Genome-Wide Association Study (GWAS) summary statistics. Using bidirectional two-sample Mendelian randomization (MR), two-step MR, and multivariable Mendelian randomization (MVMR) methods, we explored the causal relationship between gut microbiota, inflammatory proteins, and CR-NETs. Our study found that five types of gut microbiota (family Acidaminococcaceae, family Porphyromonadaceae, genus Oscillospira, genus Paraprevotella, genus Ruminococcaceae NK4A214 group) and five inflammatory mediators (C-C motif chemokine Ligand 4, C-C motif chemokine Ligand 23, TNF-related apoptosis-inducing ligand, C-X-C motif chemokine Ligand 5, Monocyte chemoattractant protein 2) have a causal relationship with CR-NETs. Additionally, C-C motif chemokine Ligand 23 (CCL23) mediated the causal effect of family Porphyromonadaceae on CR-NETs (with a mediation proportion of 6.3%), while C-C motif chemokine Ligand 4 (CCL4) mediated the causal effect of genus Ruminococcaceae NK4A214 group on CR-NETs (with a mediation proportion of 4.7%). There is a causal relationship between gut microbiota and inflammatory proteins in the development of CR-NETs, with CCL23 and CCL4 possibly playing a mediating role.