The Variation Of Gut Microbiota In Chronic Pancreatitis Mice

Objective: Chronic pancreatitis(CP)is a refractory multifactorial disease.The changes of intestinal microbiome are associated with inflammatory,metabolic,and malignant disorders.The variations of gut microbiota is still not clear in CP.Therefore,our study was to explore changes in intestinal microflora composition in mice with CP,and to further identify potential specific bacterial microflora.Methods: 18 male C57BL/6 mice were randomly selected,and divided into two groups,further,treated intraperitoneally with saline(CT group)or ethanol + cerulein(CP group)for six weeks(n = 9 mice per group).Body weight was measured in entire processes.Histopathological assays for chronic pancreatitis index along with HE and Masson staining were conducted to verify the CP induction.The composition of the gut microbiota was assessed by analyzing DNA pyrosequencing of the V4 hypervariable region of 16 S ribosomal RNA(r RNA)genes via Illumina Hi Seq sequencing.Results: The weight of mice in the experimental groups was significantly lower than control groups(P < 0.001).The analysis of the pancreatic tissue showed HE staining of the pancreas tissues revealed profound acinar loss,infiltration of inflammatory cells,enlarged interstitial spaces,glandular atrophy,degeneration and parenchyma fibrosis in the CP group.Masson staining showed extensive trichrome-positive staining in the CP group.Our results showed that intestinal microbiome disorders of CP were distinguished with reduced diversity and structural and functional variations.We observed that the gut microbial community of CP mice was characterized by a decrease in phylum Firmicutes,and an increase in phylum Bacteroidetes.Especially,microbial diversity and the ratio of Firmicutes/Bacteroidetes were significantly decreased.At the genus levels,a reduced the relative abundance of Lachnospiraceae_NK4A136,Ruminiclostridium,Roseburia,and Blautia,and increased the relative abundances of Bacteroides,Alloprevotella and Muribaculum genera.At the microbial community level,we observed that a significantly lower representation of Gram positive and containing mobile elements in the CP group.Additionally,an increased proportion of Gram negative and potentially pathogenic phenotypes in the CP mice,thereby contributing to an upregulation of lipopolysaccharide(LPS)biosynthesis.Conclusion: Intraperitoneal(IP)injections of ethanol and cerulein could successfully induce CP in mice.Chronic pancreatitis mice reduced the diversity of gut microbiota and altered its composition and functions,which suggests gut microbiota might be a novel therapeutic target for CP patients.