Alteration Of Intestinal Microbiota In Patients With Chronic Pancreatitis

Background and aim Chronic pancreatitis(CP)is a complex disease which has highly variable clinical symptomatology and disease course.This illness is characterized by repeated mild acute episodes of inflammation in the pancreas,leading to the infiltration of inflammatory cells and fibrosis,and could affect the exocrinal and endocrinal functions of pancreas.The risk of pancreatic cancer is markedly increased in patients with CP.However,the pathogenesis of CP remains poorly understood.The emergence of 16 S ribosomal RNA(r RNA)microbial profiling helps in the understanding of the human gut microbiota composition and its physiopathological role in many diseases.Several studies have characterized the intestinal microbiota in patients with CP with small sample size.At the same time,pancreatic exocrine function is an important independent factor affecting intestinal microecology,and there is no study on the correlation between pancreatic exocrine insufficiency and intestinal microecology changes in CP patients.We designed this cross-sectional study to elucidate the characteristics of the gut microbiome in patients with CP and its correlation with serum inflammatory cytokines and pancreatic exocrine function.Methods We recruited 71 patients with CP who were inpatient in the department of gastroenterology of Changhai Hospital from September 2017 to June 2018.Healthy family members who lived together with the patients were enrolled as health controls(HC,n=69).The microbiomes of fecal samples were analysed by 16 S r RNA gene profiling,using next-generation sequencing,while serum inflammatory cytokines were analysed by inflammation array.Data analysing include microbiota diversity and richness,significantly different species,metabolic pathways and correlation between microbiome and inflammatory cytokines.We also performed the detection of fecal elastase,and subgroup analysis was performed on patients with pancreatic exocrine insufficient.Results The gut microbiome of patients with CP had reduced species diversity and richness compared with that of HC.Several significantly different species were found.At the phylum level,the abundance of p?Firmicutes and p?Actinobacteria was significantly lower in CP group,while the abundance of p?Proteobacteria was significantly higher in CP group.At the genus level,the abundance of g?Escherichia-Shigella and g?Parabacteroides was significantly higher in CP group,while g?Faecalibacterium,g?Subdoligranulum,g?Dorea and g?Megamonas,et al was significantly lower in CP group.The predicted KEGG level 3 pathway lipopolysaccharide biosynthesis and bacterial invasion of epithelial cells enriched in CP group were correlated highly with g?Escherichia-Shigella(r=0.454?0.694,P<0.001).Four inflammatory cytokines were significantly different between the two groups,including IL-6?IL-8?MCP-1 and TNF-?.The spearman correlation test showed that g?Faecalibacterium was negatively correlated with serum cytokines IL-8,while g?Escherichia-Shigella was positively correlated with IL-6?IL-8?MCP-1 and TNF-?.Through the detection of fecal elastase1 in patients with CP,42 CP patients showed pancreatic exocrine dysfunction,while 28 patients showed normal pancreatic exocrine function.Further subgroup analysis of the intestinal flora of these patients showed that the diversity and composition of gut microbiota between the two groups had no significant difference,however,the abundance of g?Bifidobacterium and g?Lachnoclostridium showed significant positive correlation with the level of elsatase1.Conclusion This study contributes novel insights into the role of microbiota in the development of CP and suggests the potential relationship of gut microbiota dysbiosis with low grade inflammation in CP.It reveals the possibility that intestinal microorganisms can be used as biomarkers for the diagnosis of CP,and the supplement of beneficial bacteria or their metabolites may be a new strategy for the treatment of CP.