The Gut Microbiota Dysbiosis And Its Relationship With Organ Injury In A Rat Model Of Intra-abdominal Hypertension

Part 1: The Investigation of Gut Microbiota in a Rat Model of Intra-abdominal Hypertension Background: Intra-abdominal hypertension（IAH）and abdominal compartment syndrome（ACS）are common in critically ill patients,which have severe effects on multiple organs and cause high mortality.IAH/ACS are generally neglected by clinicians,which lead to delayed diagnosis and treatment,resulting in multiple organ injuries and eventually multiple organ dysfunction syndromes（MODS）.The intestinal tract is thought to be the initiating organ of IAH/ACS-induced MODS.The impact of IAH/ACS on the gut is a complex multiple cascade reaction involving increased permeability of bowel wall,induced intestinal barrier dysfunction,heightened bacterial translocation.The homeostasis of gut microbiota is vital to maintaining body health,while the ectopic gut microbiota has been confirmed to be associated with various organ injuries.In the first part of this study,rats were used as models to study the changes of gut microbiota after IAH intervention,laying a foundation for the subsequent study on the relationship between gut microbiota and IAH/ACS induced organ injury.Methods: The IAH model was constructed after the N2 intraperitoneal of rats,and the intra-abdominal pressure（IAP）was maintained above 20 mm Hg for 4h.The cecal feces of rats were collected for 16 S rRNA sequencing analysis,and the effects of IAH on the intestinal flora of rats were analyzed.Results: The alpha diversity of microbiota presented in this study were significantly lower in the IAH 4h group than that in the control group（P<0.05）,and the beta diversity of microbiota in the IAH 4h group was different from the control group.At the phylum level,IAH increased the relative abundance of Firmicutes and Proteobacteria species and decreased the relative abundance of Bacteroidota species.The relative abundance of Clostridia,Lachnospiraceae,Gammaproteobacteria,Proteobacteria,Escherichia_Shigella,Enterobacteriaceae,Micrococcaceae,Rothia,Oscillospiraceae,Family_XIII_UCG₀01.Conclusions: The gut microbiota dysbiosis of rats was induced by the IAH intervention.Part 2: The Relationship Between Hepatic and Intestinal Injury with the Gut Microbiota Dysbiosis in the Process of Intra-abdominal Hypertension Background: The hepatic vascular was compressed and the blood supply was reduced during the process of IAH/ACS,which attributed to liver ischemia and reperfusion injury.IAH/ACS can lead to the ectopic gut microbiota and disruption of the intestinal mucosal barrier,which interacts with the liver through the portal vein system,and the relationship between the ectopic gut microbiota with a variety of liver injuries has been confirmed.Therefore,it is speculated that gut microbiota disorder caused by IAH/ACS may result in liver injury.The relationship between gut microbiota and IAH/ACS-related liver injury was investigated in this study.Methods: Rats were intragastric with a mixture of antibiotics to eliminate gut microbiota.Fecal microbiota transplantation（FMT）was used to alter the composition of gut microbiota in rats.In addition,automatic biochemical analysis of ALT and AST,immunohistochemistry,HE staining,liver injury scoring,and Western Blot methods were used in this study.Results: The IAH 4h group rats exhibited significant intestinal mucosal barrier damage and liver function impairment.The IAH induced liver damage was alleviated by the elimination of gut microbiota and was aggravated by the FMT of the IAH 4H group rats.The JNK/ P38 signaling pathway was activated in this process.Conclusion: In addition to hepatic vascular compression,the gut microbiota also was one of the most important factors contributing to the IAH-related liver injury,and the JNK/p38 signaling pathway was activated in this process.