Copyright ©The Author(s) 2023.
World J Gastroenterol. Jan 7, 2023; 29(1): 144-156
Published online Jan 7, 2023. doi: 10.3748/wjg.v29.i1.144
Table 1 Clinical studies of gut microbiota dysbiosis in cirrhotic patients with minimal hepatic encephalopathy
Number of patients
Etiology of cirrhosis
MHE diagnosis
Microbiota alteration
Zhang et al[8]China51AIH, HBV, PBC, alcoholNCT-A DSTStool16S rRNA pyrosequencingEnriched Streptococcus salivarius
Wang et al[14]China98HBV, HCV, othersNCT-A DSTStool16S rRNA sequencingEnriched Proteobacteria, especially Pasteurellaceae Haemophilus and Alcaligenaceae Parasutterella
Luo et al[29]China143HBVPHESStool16S rRNA sequencingEnriched Streptococcus salivarius and Veillonella
Liu et al[76]China55HBV, HCV, alcohol, othersNCT-A BAEPStoolStool bacterial cultureOvergrowth of E. coli and Staphylococcus spp.
Bajaj et al[27]United States97HCV, alcohol, NASH, othersICT PHESStoolShotgun metagenomic sequencingAlistipes ihumii, Prevotella copri, and Eubacterium spp. were higher, while Enterococcus spp. were uniquely lower in MHE diagnosed by ICT
Bajaj et al[28]United States247HCV, alcohol, NASH, othersPHES ICT StroopStoolMulti-tagged sequencingEnriched Lactobacillaceae
Table 2 Clinical Studies of gut microbiota modulation in cirrhotic patients with minimal hepatic encephalopathy
Microbiota alteration
Therapeutic effect
Wang et al[14]Multi-centre, open-label, randomized controlled triallactulose (n = 67), control (n = 31)60 dStool16S rRNA sequencingHigher abundances of Bacteroidetes, Firmicutes, Actinobacteria, and Proteobacteria were in non-responders for lactuloseSignificantly ameliorated MHE
Bajaj et al[56]Controlled clinical trialMHE patients before/after rifaximin (n = 20)8 wkStoolMulti-tagged pyrosequencing, GC/LC-MSModest decrease in Veillonellaceae and increase in Eubacteriaceae, with significant changes in metabolite correlationsSignificant improvement in endotoxemia and cognition
Lactobacillus GG
Bajaj et al[74]Randomized phase I, placebo-controlled trialProbiotic (n = 14), placebo (n = 16)8 wkStoolMulti-tagged pyrosequencing, GC/LC-MSDecreased Enterobacteriaceae and increased Lachnospiraceae and Clostridiales Incertae Sedis XIV, with significant alterations in metabolite correlations with amino acid and secondary bile acid metabolismAttenuated endotoxemia and decreased TNF-α without change in cognition
Clostridium butyricum combined with Bifidobacterium infantis
Xia et al[73]Randomized controlled trialProbiotic (n = 30), placebo (n = 37)3 moStool16S rRNA sequencingIncreased Clostridium cluster I and Bifidobacterium, decreased Enterobacteriaceae and EnterococcusReduced ammonia and improved cognition
Escherichia coli Nissle 1917 strain
Manzhalii et al[75]Single-centre, open-label, randomized trialProbiotic (n = 15), lactulose (n = 15), rifaximin (n = 15)1 moStool16S rRNA sequencingNormalized Bifidobacterium and Lactobacilli abundanceReduced ammonia and pro-inflammatory cytokines and improved cognition
Rifaximin plus probiotic
Zuo et al[84]Controlled clinical trialRifaximin (n = 7), rifaximin plus probiotic (n = 7)4 wkStool16S rRNA sequencingBoth treatments alone reduced the overall microbiome diversity, with decreased Streptococcus and Faecalibacterium, Clostridium and increased LactobacillusRifaximin plus probiotics showed a more apparent effect
Rifaximin plus lactulose
Schulz et al[72]Randomized controlled trialRifaximin (n = 1), rifaximin plus lactulose (n = 4)3 moStool16S rRNA sequencingRifaximin with or without lactulose did not affect microbiota compositionMHE improvement with rifaximin lasted after the end of treatment
Probiotics plus fermentable fiber
Liu et al[76]Controlled clinical trialSynbiotic (n = 20), fermentable fiber (n = 20), placebo (n = 15)30 dStoolStool quantitative bacteriological cultureSignificant increase in non-urease-producing Lactobacillus speciesReduced ammonia and endotoxemia levels, reversal in 50% of MHE patients