Alterations in the intestinal microbiome and metabolic profile of patients with cirrhosis supplemented with lactulose, Clostridium butyricum, and Bifidobacterium longum infantis: a randomized placebo-controlled trial

Abstract

BackgroundLiver cirrhosis is commonly accompanied by intestinal dysbiosis and metabolic defects. Many clinical trials have shown microbiota-targeting strategies represent promising interventions for managing cirrhosis and its complications. However, the influences of the intestinal metagenomes and metabolic profiles of patients have not been fully elucidated.MethodsWe administered lactulose, Clostridium butyricum, and Bifidobacterium longum infantis as a synbiotic and used shotgun metagenomics and non-targeted metabolomics to characterize the results.ResultsPatients treated with the synbiotic for 12 weeks had lower dysbiosis index (DI) scores than placebo-treated patients and patients at baseline (NIP group). We identified 48 bacterial taxa enriched in the various groups, 66 differentially expressed genes, 18 differentially expressed virulence factor genes, 10 differentially expressed carbohydrate-active enzyme genes, and 173 metabolites present at differing concentrations in the Synbiotic versus Placebo group, and the Synbiotic versus NIP group. And Bifidobacteria species, especially B. longum, showed positive associations with many differentially expressed genes in synbiotic-treated patients. Metabolites pathway enrichment analysis showed that synbiotic significantly affected purine metabolism and aminoacyl-tRNA biosynthesis. And the purine metabolism and aminoacyl-tRNA biosynthesis were no longer significant differences in the Synbiotic group versus the healthy controls group. In conclusion, although littles influence on clinical parameters in the early intervention, the synbiotic showed a potential benefit to patients by ameliorating intestinal dysbiosis and metabolic defects; and the DI of intestinal microbiota is useful for the evaluation of the effect of clinical microbiota-targeting strategies on cirrhotic patients.Clinical Trial Registrationhttps://www.clinicaltrials.gov, identifiers NCT05687409.

The Impact of Probiotic Bifidobacterium on Liver Diseases and the Microbiota

“…They observed an elevation in B. breve and C. butyricum levels and a reduction in K. pneumoniae. Consequently, there was an enhancement in lipopolysaccharide (LPS) degradation metabolism, an upsurge in butyric acid levels in peripheral blood, and an ultimate improvement in the inflammatory profile [23]. Parallel findings were reported in an animal model by Gómez-Hurtado.…”

“…Collectively, the articles reviewed in this study all aligned in the same direction: Bifidobacterium acts beneficially as a probiotic in NAFLD, ALD, and Cirrhosis. It does so by restoring the intestinal microbiota balance, reducing inflammation and oxidative [23,[28][29][30], whereas (B) represents the same for animal studies [19][20][21][22][24][25][26][27]. The letter "D" denotes the domains present in the checklists.…”

“…SILVA, Greengenes, and Ribosomal Data Project (RDP) were the databases most frequently utilized in the research. Additionally, four studies did not report the database used [19,[23][24][25]. The lack of information in the methodology about the database used and the use of obsolete databases, such as Greengenes, is quite concerning.…”

“…However, none of the studies included in this review used ANCOM/ANCOM-BC. Only six studies used LEfSe to compare taxonomic abundance between groups [21,[23][24][25]27,29]. Four studies have relied on simpler statistical methods, such as Kruskal-Wallis and Mann-Whitney [20,22,28,30].…”

Gut microbes combined with metabolomics reveal the protective effects of Qijia Rougan decoction against CCl4-induced hepatic fibrosis

“…Numerous studies have demonstrated that botanical drugs and their extracts are capable of suppressing HF by restoring enteric barriers and modulating intestinal dysbacteriosis and metabolites ( Zhao J. et al, 2021 ; Hu et al, 2021 ; Fu et al, 2022 ; Liu et al, 2022 ; Yue et al, 2022 ; Zheng et al, 2022 ; Chang et al, 2023 ; Guo et al, 2023 ; Hu et al, 2023 ). Studies have suggested that probiotics such as Lactobacillus GG ( Bajaj et al, 2014 ), Bacteroides dorei ( Park et al, 2023 ), Clostridium butyricum and Bifidobacterium longum infantis ( Lu et al, 2023 ), as well as gut microbial metabolites such as indole-3-propionic acid ( Sehgal et al, 2021 ; Yuan et al, 2023 ) and Trimethylamine N-oxide ( Zhou D. et al, 2022 ; Nian et al, 2023 ), are beneficial in HF.…”