Comparative study of gut microbiota and metabolite variations between severe and mild acute pancreatitis patients at different stages

Abstract

Acute pancreatitis (AP) is influenced by interactions between gut microbiota and metabolic products, though the mechanisms remain unclear. This study investigates variations in gut microbiota and metabolites between severe (SAP) and mild acute pancreatitis (MAP) patients to assess their impact on disease progression. Using a cross-sectional cohort design, gut microbiota and metabolite profiles were compared in SAP and MAP patients over two weeks post-diagnosis. 16S rRNA gene sequencing and metabolomic analyses, including KEGG pathway assessments and Spearman correlation, were employed, along with Mendelian Randomization (MR) to assess the influence of specific microbiota on AP. Results showed that SAP patients had significantly reduced gut microbiota diversity, which further declined in the second week. This was marked by increases in pathogenic bacteria like Stenotrophomonas and Enterobacter and decreases in beneficial bacteria such as Blautia. Key changes included a rise in Proteobacteria and a decline in Ruminococcaceae, Enterococcus, and Faecalicatena. Metabolic shifts included lipid metabolite upregulation and antioxidant downregulation. Correlation analysis linked Stenotrophomonas to short-chain fatty acid and amino acid metabolism, highlighting its role in disease progression. MR analysis confirmed negative causal relationships between Enterococcus B, Faecalicatena torques, and AP, suggesting protective effects. Variations in Blautia species indicated differing influences on AP. This study underscores the critical role of gut microbiota and metabolites in AP progression and suggests the need for further research to confirm these findings and explore targeted therapeutic interventions.