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Potential causal association between gut microbiota, inflammatory cytokines, and acute pancreatitis: A Mendelian

Xiaofeng Wang1,2, Yiwen Qiu3, Ying Di4

  • 1Department of Critical Care Medicine, Tangdu Hospital, Air Force Medical University, Xi'an, Shaanxi, China.

Journal of Intensive Medicine
|April 17, 2025
PubMed
Abstract

Insights

This study found specific gut bacteria linked to acute pancreatitis (AP) risk. While some bacteria increase AP risk, others decrease it, but inflammatory cytokines don't mediate this connection.

Area of Science:

  • Gastroenterology
  • Genetics
  • Microbiome Research

Background:

  • Acute pancreatitis (AP) is a common gastrointestinal emergency.
  • Emerging evidence highlights the interplay between gut microbiota (GM), inflammatory cytokines, and AP development.

Purpose of the Study:

  • To investigate the potential causal relationships between gut microbiota, inflammatory cytokines, and acute pancreatitis using Mendelian randomization.
  • To explore the mediating role of inflammatory cytokines in the gut microbiota-AP axis.

Main Methods:

  • A two-sample Mendelian randomization (MR) study utilized summary statistics for GM (n=18,340), cytokines (n=8293), and AP (3022 cases, 195,144 controls).
  • Inverse variance weighted (IVW) method was primary, with MR-Egger and weighted median as sensitivity analyses.
  • Sensitivity analyses included Cochran's Q-test, MR-Egger intercept, leave-one-out, and MR-PRESSO to assess pleiotropy and heterogeneity.

Main Results:

  • Several GM taxa showed significant associations with AP risk: Bacteroidales, Eubacterium fissicatena group, and Coprococcus3 were positively associated, while Prevotella9, RuminococcaceaeUCG004, and Ruminiclostridium6 were negatively associated.
  • Macrophage colony-stimulating factor (M-CSF) was the only cytokine negatively associated with AP.
  • Mediation analysis indicated M-CSF did not mediate the relationship between GM and AP.

Conclusions:

  • Specific gut microbiota compositions are causally associated with acute pancreatitis risk.
  • While M-CSF shows an inverse association with AP, it does not mediate the effects of gut microbiota on AP development.
Keywords:
Acute pancreatitisGut microbiotaInflammatory cytokinesMediation analysisMendelian randomization

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