The Role And Mechanism Of Gut Microbiota In The Onset And Development Of Acute Pancreatitis With Obesity

Background The incidence of acute pancreatitis is rising with the years,but its pathogenesis is not fully understood.The treatment still tends to be symptomatic and supportive.And obesity patients can significantly aggravate the severity of pancreatitis and increase the rate of re-admission.Therefore,it is of vital importance to explore the mechanism of how obesity accelerates pancreatitis.The current research on the relationship between gut microbiota and obesity has gradually become clear.There is an interaction between the gut microbiota and obesity,and the disturbance of gut microbiota can directly cause obesity.So,will the disturbance of gut microbiota affect the development of pancreatitis with obesity? This study tends to explore the role and possible pathogenesis of the gut microbiota in the progression of pancreatitis with obesity through a series of experiments so as to provide new ideas for the prevention and treatment of pancreatitis.Objectives To explore the role and possible mechanisms of gut microbiota in the progression of pancreatitis with obesity.Methods 1.Obese mice models tried to stimulate people’s obesity status by studying obese mice with high-fat diet.And then intermittent intraperitoneal injection of cerulein was applied to obese mice models so as to evaluate the severity of pancreatitis in obese mice.2.The combination of four antibiotics(ampicillin,neomycin,metronidazole,and vancomycin)was used to intervene the gut microbiota which could dramatically decrease its diversity in mice,and the combination’s effect on the severity of pancreatitis was also studied.3.Vancomycin was used to intervene the gut microbiota in mice,and then we observed its effect on the severity of pancreatitis.4.PICRUST was used to predict the functions of differential bacteria in pancreatitis in obese mice and normal weight mice respectively.Results 1.Serum amylase,serum lipase,pancreatic tissue water content and MPO activity significantly elevated in obese mice with pancreatitis,and HE staining of pancreatic tissue showed increased infiltration of inflammatory cells and increased marginal necrosis.2.After the administration of the combination of four antibiotics,gut microbiota in mice decreased significantly in each group,especially in those obese mice.We then used cerulein to induce pancreatitis and found that the combination of four antibiotics can relieve serum amylase,serum lipase,pancreatic edema,and inflammatory cell infiltration in obese mice.3.Vancomycin could reduce the diversity of fecal microorganism,which mainly showed gram-positive bacteria(mainly Firmicutes bacteria).However,there was an increase of Firmicutes but a decline in Bacteroidetes in obese mice.Oral vancomycin in obese mice partially reversed the disturbance of gut microbiota,which effectively relieve the severity of pancreatitis.4.By comparing the differential gut microbiota between obese pancreatitis and normal pancreatitis in mice,we used PICRUST to predict and found that some lipid metabolism,energy metabolism,adipokine synthesis,and cell death may be closely involved.However,those above-mentioned pathways were partially reversed after the intervention of antibiotics(especially vancomycin).Conclusion 1.Obesity can aggravate the severity of pancreatitis in the mouse model.2.Oral administration of four antibiotics declines the severity of pancreatitis in obese mice.3.Oral vancomycin can significantly decline the severity of pancreatitis in obese mice.4.The disturbance of gut microbiota in obese mice may cause abnormalities in lipid metabolism,energy metabolism,adiponectin synthesis,and cell death,resulting in the activation of inflammatory pathways and secretion of large amounts of pro-inflammatory cytokines into the blood circulation,which will aggravate the severity of pancreatitis.