Abstract
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.