Clostridium butyricum Strains Suppress Experimental Acute Pancreatitis by Maintaining Intestinal Homeostasis

Acute pancreatitis (AP) is a common abdominal inflammatory disease. Disturbed gut homeostasis secondary to pancreatic inflammation aggravates the condition retroactively. The current study investigates potential beneficial effects of Clostridium butyricum (C. butyricum) strains on AP and underlying mechanisms.C. butyricum strains MIYAIRI 588 (CBM588) and CGMCC0313.1 (CB0313.1) were supplemented to mice for three weeks before experimental AP or SAP induction. Both CBM588 and CB0313.1 protected against AP, as evidenced by reduced serum amylase and lipase levels, pancreatic edema, and myeloperoxidase activity. Amelioration of both experimental AP and SAP by CB0313.1 indicated a non-model-specific effect. Moreover, C. butyricum inhibited pancreatic neutrophil and dendritic cell infiltration, nucleotide-binding domain leucine-rich repeat-containing family, pyrin domain-containing 3 inflammasome activation, and pro-inflammatory pathways. Additionally in the gut, C. butyricum strains attenuated AP-associated intestinal inflammation and barrier dysfunction, accompanied with reduced pathogenic bacteria Escherichia coli and Enterococcus penetration into pancreas. Gut microbiome analyses further revealed that beneficial effects of C. butyricum on pancreatic-gut homeostasis were correlated with improved dysbiosis. In particular, relative abundance of Desulfovibrionaceae decreased, and Verrucomicrobiaceae Clostridiaceae and Lactobacillaceae increased.For the first time, a protective effect of C. butyricum in AP by modulating intestinal homeostasis is demonstrated.