Diet, gut microbiome and their end-metabolites associate with acute pancreatitis risk

Introduction Diet and decreased gut microbiome diversity has been associated with acute pancreatitis (AP) risk. However, differences in dietary intake, gut microbiome and their impact on microbial end-metabolites have not been studied in AP. We aimed to determine differences in i) dietary intake ii) gut microbiome diversity and sulfidogenic bacterial abundance, and iii) serum short-chain fatty acid (SCFA) and hydrogen sulfide (H₂S) concentrations in AP and control subjects. Methods This case-control study recruited 54 AP and 46 control subjects during hospitalization. Clinical and diet data, stool and blood samples were collected. 16S rDNA sequencing was used to determine gut microbiome alpha diversity and composition. Serum SCFA and H₂S levels were measured. Machine learning (ML) model was used to identify microbial targets associated with AP. Results AP patients had decreased intake of vitamin D3, whole grains, fish, and beneficial eicosapentaenoic, docosapentaenoic, and docosahexaenoic acids. AP patients also had lower gut microbiome diversity (p=0.021) and higher abundance of sulfidogenic bacteria including Veillonella and Haemophilus which were associated with AP risk. Serum acetate and H₂S concentrations were significantly higher in the AP group (p < 0.001 and p=0.043, respectively). ML model had 96% predictive ability to distinguish AP patients from controls. Conclusions AP patients have decreased beneficial nutrient intake and gut microbiome diversity. Increased abundance of H₂S producing genera in the AP, SCFA producing genera in the control group, and predictive ability of ML model to distinguish AP patients indicates that diet, gut microbiota and their end-metabolites play a key role in AP.