Correlation between gut microbiota and pancreatitis: a bidirectional Mendelian randomization.

Objective: The causative role of gut microbiota in pancreatitis remains unknown. This study aimed to investigate potential causal associations between gut microbiota and pancreatitis, using bidirectional Mendelian randomization (MR) analysis.

Methods: We analyzed genome-wide association study (GWAS) summary statistics for gut microbiota (211 taxa from gut microbiota, n = 18 340) and two types of pancreatitis, namely acute pancreatitis (AP, 5509 cases and 301 383 controls) and chronic pancreatitis (CP, 3002 cases and 301 383 controls). A reverse MR analysis was also performed to assess the possibility of reverse causation.

Results: Nine features (one family + eight genera) showed a causal association with AP. According to inverse-variance weighted (IVW) estimates, phylum Firmicutes (P = 4.10 × 10-2), genus Erysipelatoclostridium (P = 4.80 × 10-2), genus Flavonifractor (P = 4.10 × 10-2), genus Methanobrevibacter (P = 3.40 × 10-2), and genus Prevotella9 (P = 4.60 × 10-2) were found to have a protective effect on AP. Additionally, genus Eubacteriumeligensgroup (P = 4.10 × 10-2), genus Eubacteriumfissicatenagroup (P = 4.00 × 10-3), genus Coprococcus3 (P = 4.10 × 10-2), and genus Haemophilus (P = 4.60 × 10-2) exhibited a positive correlation with AP. Four features (two families + two genera) were causally associated with CP. IVW results also confirmed that family Clostridiaceae1 (P = 3.30 × 10-2), genus LachnospiraceaeFCS020group (P = 4.60 × 10-2), and genus Prevotella9 (P = 1.90 × 10-2) were protective factors for CP, whereas the presence of family Victivallaceae (P = 2.60 × 10-2) correlated with CP risk. No causal effects of pancreatitis (AP or CP) on these gut microbiota taxa were found in the reverse MR analysis.

Conclusion: This study confirms a potential causal relationship between gut microbiota and pancreatitis, highlighting the gut microbiota-pancreas axis in the pathogenesis of pancreatitis.