Meta-analysis Of The Effects Of Probiotics On Liver Injury And Glycolipid Metabolism In Adult Patients With Nonalcoholic Fatty Liver Disease

Background:In recent years,the incidence of Non-alcoholic fatty liver disease(NAFLD)is increasing worldwide.However,the treatment strategy for NAFLD is still unclear.Objective:This study aims to analyze and study the effects of probiotics on serum biochemical indexes and inflammatory factors in adult patients with non-alcoholic fatty liver disease.Methord:We searched in Pubmed,Embase,Web of science and FMRS databases,screened literatures and extracted relevant data according to the established standards.It included literature year,author information,number of patients in the treatment group and control group,age of patients in the treatment group,intervention measures in the control group,probiotic species,and treatment period,and serum liver enzyme markers(ALT、AST、γ-GT、ALP),lipid markers(TC、TG、HDL、LDL),blood glucose markers(GLU、Hb A1c、Insulin、HOMA-IR)and serum inflammatory factor markers(TNF-α、IL-β、IL-8、IL-6);The risk of literature bias was evaluated according to the Cochrane risk assessment tool,and the meta-analysis of each indicator was performed by the Review Manager v.5.4 software and the results were obtained.Results:A total of 14 randomized clinical trials involving 365 adults with NAFLD were included in this study.1.In the primary outcomes,we’ve got:ALT:MD=-6.36(95%CI:-11.00—-1.71,P=0.007);AST:MD=-5.36(95%CI:-10.56—-0.17,P=0.04);γ-GT:MD=-5.94(95%CI:-7.11—-4.77,P<0.00001);ALP:MD=-33.17(95%CI:-42.72—-23.61,P<0.00001);HDL:MD=-0.07(95%CI:-0.13—-0.01,P=0.03).It was concluded that probiotics could significantly reduce serum ALT,AST,ALP and HDL in patients with NAFLD,but had no significant effect on reducing serum γ-GT,TG,TC and LDL.2.In the secondary outcomes,we’ve got:GLU:MD=0.66(95%CI:0.03—1.30,P=0.04);Hb A1c:MD=-0.12(95%CI:-0.19—-0.05,P=0.0004);HOMA-IR:MD=-1.24(95%CI:-1.53—-0.95,P<0.00001),However,there was no significant improvement on serum Insulin,TNF-α,IL-6,IL-1β and IL-8,so the study showed that probiotics treatment can effectively reduce blood glucose,glycosylated hemoglobin and insulin resistance in NAFLD patients.3.In addition,through subgroup analysis,we found that:A 12-week course of probiotic therapy significantly reduced serum markers’ level in NAFLD patients:ALT(MD=-10.74,95%CI:-12.35—-9.13,I~2=4%,P<0.00001)、AST(MD=-6.25,95%CI:-9.41—-3.09,I~2=20%,P=0.0001)、和 TC(MD=-10.05,95%CI:-15.81—-4.28,I~2=0%,P=0.0006).Meanwhile,TG(MD=0.40,95%CI:0.07—0.72,I~2=0%,P=0.02)and TC(MD=0.26,95%CI:0.05—0.46,I~2=0%,P=0.01)showed the same significant results after 8 weeks of treatment.Using probiotics as subgroup for analysis,we concluded that the serum ALT and AST of NAFLD patients treated with VSL#3(?) and Lactobacillus and Bifidobacterium were significantly improved,and the combined treatment with the two probiotics was also effective in reducing serum ALT and AST.Conclusion:1.This study found that probiotics could effectively improve serum liver enzymes(ALT,AST,ALP),blood lipid(HDL)and glucose metabolism(GLU,Hb A1 c,HOMA-IR)in adult patients with NAFLD;2.Subgroup analysis showed that:(1)12 weeks of probiotics could effectively reduce serum ALT,AST,and TC in NAFLD patients,and 8 weeks of probiotics could also effectively reduce serum TC and TG in NAFLD patients.(2)The use of VSL#3(?) and Lactobacillus and Bifidobacterium in the treatment of adult NAFLD patients can effectively reduce the serum ALT and AST,and the combined use of the two probiotics also has a significant effect;3.This study has certain limitations.Due to the small number of literatures included,the small clinical sample size to support the results obtained by our analysis,and the heterogeneity among various studies,we still need to conduct more clinical trials to obtain data to repeatedly verify these results and analyze the relationship between them;4.In the subgroup analysis,we found that 12 weeks of probiotic treatment cycle has significant effects on reducing serum liver enzymes and blood lipids,and VSL#3(?) and Lactobacillus and Bifidobacterium also have significant effects on improving serum ALT and AST in adult patients with NAFLD.These may be good research directions,which can provide new ideas for first-line clinical treatment.