Correlation Of Intestinal Flora And Group 3 Innate Lymphoid Cell And Wilson Disease

Objective:Wilson Disease(WD)is a copper ion metabolic disorder caused by ATP7 B gene mutation,mainly involving the liver and central nervous system.In recent years,the research of intestinal flora and central nervous system diseases has been continuously in-depth.Studies have found that there is a significant difference in the intestinal flora in WD patients with health groups,but the correlation between intestinal flora and WD clinical manifestations and severity,and the related mechanism of the intestinal flora in the WD is still unclear.The Group 3 Innate Lymphoid Cell(ILC3)are new types of immune cells that are mainly present in the intestinal mucosal tissue and regulated by intestinal flora.Studies have found that ILC3 is related to experimental autoimmune cerebral spinaliitis,multiple hardening,ischemic strokes,etc.The combination of combination,as well as the effects of drugs cause immune dysfunction.At present,the correlation of ILC3 and WD is unclear.To this end,this study plans to study the relevance of intestinal flora,ILC3 and WD symptoms and severity,and initially explore the potential mechanism of intestinal flora in the influence of WD.Methods:1.Collect from December 20020 to WD patients in the neurology hospitalization of the First Affiliated Hospital of Guangdong Pharmaceutical University,the fecal specimen and the peripheral blood specimen of the health group matching the age and gender,respectively Measurement sequencing and flow cell testing.2.Collect WD patients,age,gender,blood routine,serum copper,urine copper,copper blue protein,blood lipid,liver function,hepatic fiber,hepatitis special enzyme,blood ammonia,renal function,coagulation function,liver B-ultrasound and other clinical data.By two high-year-old,the above-mentioned physician assists the assessment scale,collecting the following quantities of WD patients: Unified Wilson’s Disease Rating Scale(UWDRS),Child-Pugh Score,Standard Swallow function evaluation scale(SSA),8 drug treatment compliance,and the like.3.Analysis of the difference in species structure,abundance between the intestinal flora and health control group,analyzed the severity of WD disease and the correlation between the clinical manifestations of intestinal bacteria.4.Analyze the correlation between intestinal bacterial abundance and peripheral blood ILCs and its subsequent blood in patients with WD.5.Analysis of the correlation between peripheral blood ILC3 ratio and WD disease severity and clinical manifestations of WD disease.Result:1.The fecal specimens were included in 92 patients and 53 cases in the control group.Blood label for streaming cells was included in 59 cases and45 cases of control groups in WD groups.There was no significant difference in gender and age in two groups(P > 0.05).2.Analysis of the α diversity and β diversity of the intestinal flora group of the WD group and the health control group,found that the intestinal floraα diversity analysis between WD group and health control group was allocated.There was a significant difference(P <0.05),Principal Component Analysis,PCOA in the β diversity of the WD group and the healthy control group,the results showed significant statistical significance(P <0.05).3.After comparing the intestinal flora in the WD group of the health control group,there was a significant difference in the flora in the WD group and the health control group.The WD group was bifidobacterium,Escherichia-shigella,Streptococcus,Collinsella,Ruminoccus＿gnavus＿group,Megasphaera,Lachnoclostridium was significantly more than the health control group(P <0.05),Bacteroides,Faecalibacterium,Triacolactobacterium,unclassified＿F＿Lachnospiraceae),Fusobacterium,Roseburia,Agathobacter,Norank＿f＿eubacterium＿Coprostanoligenes＿group significantly less than healthy control group(P <0.05).4.The correlation of WD disease severity,clinical manifestations and intestinal flora abundance showed that UWDRS(PART-II)score and Childpugh score were positively correlated with the abundance of Veillonella,Serum type III procollagen amino terminal peptide and UWDRS(PART-II)score were negatively correlated with the abundance of Ruminococcus,Child-pugh score and aspartate aminotransferase(AST)were negatively correlated with the abundance of norank＿f＿Ruminococcaceae,UWDRS(PART-I)score,UWDRS(PART-II)score and serum hyaluronic acid were negatively correlated with the abundance of unclassified＿f＿Lachnospiraceae.5.The correlation analysis of ILCs and the abundance of intestinal bacteria in WD patients showed that the proportion of ILCs in peripheral blood was negatively correlated with the abundance of Veillonella and Lactobacillus,The peripheral blood ILC2 ratio was positively correlated with the abundance of Fusobacterium,The proportion of ILC3 in peripheral blood was positively associated with the abundance of Parabacteroides and Eubacterium＿eligens＿group,The proportion of ILC3 in peripheral blood negatively correlated with the abundance of Escherichia-Shigella,Blautia,Ruminococcus＿gnavus＿group and Fusobacterium.6.The ratio of peripheral blood ILC3 was significantly higher than that of the health control(P <0.05),but ILCs,ILC1,ILC2 was not significantly different from the health control group(P >0.05).7.The ratio of peripheral blood ILC3 was positively correlated with the international normalized ratio(INR),prothrombin time(PT),blood ammonia and UWDRS(Part II)score.The ratio of peripheral blood ILC3 was negatively correlated with red blood cells,platelets,hemoglobin,triglyceride,total cholesterol,uric acid,serum fibronectin protein and thrombin activity(P <0.05).There was no significant correlation between residual laboratory indicators and peripheral blood ILC3 ratio(P >0.05).Conclusion:1.The diversity of intestinal flora in WD was significantly lower than that of the health control group,and the structure of WD patients and health control groups had significant differences,suggesting that WD is in the intestinal flora disorder.2.The abundance of WD patients including intestinal Bacteroides,Veillonella,Ruminococcus＿gnavus＿group,norank＿f＿Ruminococcaceae,unclassified＿f＿Lachnospiraceae and Blautia were negatively correlated with the severity of the disease.3.The proportion of ILC3 in WD patients was significantly increased and correlated with disease severity,among which the proportion of ILC3 was positively correlated with INR,PT,blood ammonia and UWDRS(PART II)score.the proportion of ILC3 negatively correlated with red blood cells,platelets,hemoglobin,triglycerides,total cholesterol,uric acid,serum fibronectin and prothrombin activity.4.The peripheral blood ILC3 ratio was negatively correlated with the abundance of Blautia and Ruminococcus＿gnavus＿group,suggesting that the intestinal flora Ruminococcus＿gnavus＿group and Blautia may have further protective effects against the disease by inhibiting ILC3.