Studies On Improvement Of Intestinal Flora, Intestinal Barrier And Liver Functions In Cirrhosis Patients With Probiotics

BackgroundLiver cirrhosis is a late-stage condition for a variety of chronic liver diseases. The main clinical performance of cirrhosis decreases liver function and portal hypertension and often appears lots of complications.Cirrhosis has become a serious disease that affects people’s health and economy. The fundamental treatment of cirrhosis is against the cause、liver protection and complications.Since the establishment of the bowel-liver axis theory in recent years, probiotics,as an microecologics,get more and more attention by domestic and overseas.There were lots of clinical studies about the use of probiotics for cirrhotic patients which were mainly applied in hepatic encephalopathy,these studies more emphasized on the improvement by probiotics in intestinal barrier function、inflammatory factors and liver function, but there were less clinical application of probiotics in the mechanism about intestinal flora、intestinal barrier function and inflammatory factors.On one hand evaluating the effect of probiotics in patients with liver cirrhosis for the relative researches in home and abroad by meta-analysis, on the other hand, my studies focus on the effect of the probiotics on intestinal flora, intestinal barrier and inflammatory factors for cirrhotic patients with HBV by detecting five intestinal flora and four inflammatory factors.Objectives1. To observe the effect of the probiotics on intestinal flora, intestinal barrier and inflammatory factors for cirrhotic patients with HBV.2. To evaluate the effect of probiotics in patients with liver cirrhosis by meta analysis.MethodsPart I A total of 40 patients with hepatitis B cirrhosis were enrolled in this study.Patients were randomly assigned into probiotics group (20 cases) and control group (20 cases).All patients were given conventional treatment,probiotics group received Bacillus licheniformis(0.5g tid) for 28 days in addition to conventional treatment. To observe the change of the factors of two groups before and 7 days、28 days after the therapies.By SYBY Green of real time quantitative PCR technology to detect the relative content of Bifidobacterium、Lactobacillus、Enterobacterium、 Enterococcus、Candida albicans in intestinal flora and by using enzyme-linked innunosorbent (EL1SA) to detect the content of ET、DAO、TNF-α and IL-6 in two groups.To analysize those data by SPSS 16.0 software,count data use repeated measurements analysis of variance.Part Ⅱ MEDLINE、EMBASE. The Cochrane Cental Register of Controlled Trials were searched to retrieve randomized controlled trials about the effect of probiotics in the treatment of liver cirrhosis.Statistical analysis was performed by using Review Manager 5.2software.ResultsPart Ⅰ There were no significant difference of five intestinal flora between two groups before treatment (p>0.05).Bifidobacterium of the probiotic group were significantly increased while the monilia albican were significantly decreased when compared between before and 28 days treatment compared with the control group (p <0.05).The concentration of ET in the probiotic group were significantly decreased than the concentration in the control group when compared after 28 days treatment (p <0.05). The concentration of DAO in the probiotic group were significantly decreased than the controls when compared after 28 days treatment (p<0.05).The concentration of TNF-α in the probiotic group were significantly decreased than the controls when compared after 28 days treatment (p<0.05).The concentration of IL-6 in the probiotic group were significantly decreased than the controls when compared after 28 days treatment (p<0.05)Part Ⅱ Fifty RCTs were included in all. Probiotics significantly decreased serum ALT (WMD=9.83, P=0.0005),AST (WMD=7.43, P=0.0001),ammonia (SMD=0.89, P<0.00001),endotoxin(ET) (SMD=0.81, P<0.00001),urine lactulose/mannitol ratios (WMD=0.02, P<0.002)、diamine oxidase(DAO) (SMD=0.59, P,0.0008)、TNF-α(SMD=3.28, P<0.0001) and shortened the time of completing NCT-A (WMD=9.60, P<0.00001) in patients with cirrhosis.There were significant difference for the reduce of the morbidities of small intestinal bacterial overgrowth(SIBO) (RR=0.49, P<0.0001),hepatic encephalopathy(HE) (RR=0.52, P<0.00001) and spontaneous bacterial peritonitis(SBP)(RR=0.49, P<0.0001) compared to control group in cirrhosis patients.Conclusions1. Bacillus licheniformis can significantly increase the concentration of bifidobacterium while decrease monilia albican on cirrhotic patients with HBV. Bacillus licheniformis can significantly improve the concentration of ET and DAO representing intestinal barrier and the concentration of TNF-α and IL-6 representing inflammatory factors for cirrhotic patients with HBV. It shows that probiotics can be used for the prevention and treatment of HE and SBP for cirrhotic patients with HBV.2. Meta analysis shows that probiotics can significantly decrease the levels of DAO、urine lactulose/mannitol ratios and ET to improve the intestinal barrier function and endotoxemia and decrease the levels of TNF-α to improve those biochemical indexes of ALT、AST and decrease the risk of SIBO、HE and SBP by regulating the intestinal flora.