Background Although microbioa‐based therapies have shown putative effects on the treatment of non‐alcoholic fatty liver disease (NAFLD), it is not clear how microbiota‐derived metabolites contribute to the prevention of NAFLD. We explored the metabolomic signature of Lactobacillus lactis and Pediococcus pentosaceus in NAFLD mice and its association in NAFLD patients. Methods We used Western diet‐induced NAFLD mice, and L. lactis and P. pentosaceus were administered to animals in the drinking water at a concentration of 10 9 CFU/g for 8 weeks. NAFLD severity was determined based on liver/body weight, pathology and biochemistry markers. Caecal samples were collected for the metagenomics by 16S rRNA sequencing. Metabolite profiles were obtained from caecum, liver and serum. Human stool samples (healthy control [ n = 22] and NAFLD patients [ n = 23]) were collected to investigate clinical reproducibility for microbiota‐derived metabolites signature and metabolomics biomarker. Results L. lactis and P. pentosaceus supplementation effectively normalized weight ratio, NAFLD activity score, biochemical markers, cytokines and gut‐tight junction. While faecal microbiota varied according to the different treatments, key metabolic features including short chain fatty acids (SCFAs), bile acids (BAs) and tryptophan metabolites were analogously restored by both probiotic supplementations. The protective effects of indole compounds were validated with in vitro and in vivo models, including anti‐inflammatory effects. The metabolomic signatures were replicated in NAFLD patients, accompanied by the comparable levels of Firmicutes / Bacteroidetes ratio, which was significantly higher (4.3) compared with control (0.6). Besides, the consequent biomarker panel with six stool metabolites (indole, BAs, and SCFAs) showed 0.922 (area under the curve) in the diagnosis of NAFLD. Conclusions NAFLD progression was robustly associated with metabolic dys‐regulations in the SCFAs, bile acid and indole compounds, and NAFLD can be accurately diagnosed using the metabolites. L. lactis and P. pentosaceus ameliorate NAFLD progression by modulating gut metagenomic and metabolic environment, particularly tryptophan pathway, of the gut‐liver axis.

Over the past decade, scientific evidence for the properties, functions, and beneficial effects of probiotics for humans has continued to accumulate. Interest in the use of probiotics for humans has increased tremendously. Among various microorganisms, probiotics using bacteria have been widely studied and commercialized, and, among them, Lactobacillus is representative. This genus contains about 300 species of bacteria (recently differentiated into 23 genera) and countless strains have been reported. They improved a wide range of diseases including liver disease, gastrointestinal diseases, respiratory diseases, and autoimmune diseases. Here, we intend to discuss in depth the genus Lactobacillus as a representative probiotic for chronic liver diseases.

Hepatic encephalopathy (HE) is a serious complication of cirrhosis that causes neuropsychiatric problems, such as cognitive dysfunction and movement disorders. The link between the microbiota and the host plays a key role in the pathogenesis of HE. The link between the gut microbiome and disease can be positively utilized not only in the diagnosis area of HE but also in the treatment area. Probiotics and prebiotics aim to resolve gut dysbiosis and increase beneficial microbial taxa, while fecal microbiota transplantation aims to address gut dysbiosis through transplantation (FMT) of the gut microbiome from healthy donors. Antibiotics, such as rifaximin, aim to improve cognitive function and hyperammonemia by targeting harmful taxa. Current treatment regimens for HE have achieved some success in treatment by targeting the gut microbiota, however, are still accompanied by limitations and problems. A focused approach should be placed on the establishment of personalized trial designs and therapies for the improvement of future care. This narrative review identifies factors negatively influencing the gut–hepatic–brain axis leading to HE in cirrhosis and explores their relationship with the gut microbiome. We also focused on the evaluation of reported clinical studies on the management and improvement of HE patients with a particular focus on microbiome-targeted therapy.

Emerging evidences about gut-microbial modulation have been accumulated in the treatment of nonalcoholic fatty liver disease (NAFLD). We evaluated the effect of Bifidobacterium breve and Bifidobacterium longum on the NAFLD pathology and explore the molecular mechanisms based on multi-omics approaches. Human stool analysis [healthy subjects (n = 25) and NAFLD patients (n = 32)] was performed to select NAFLD-associated microbiota. Six-week-old male C57BL/6 J mice were fed a normal chow diet (NC), Western diet (WD), and WD with B. breve (BB) or B. longum (BL; 109 CFU/g) for 8 weeks. Liver/body weight ratio, histopathology, serum/tool analysis, 16S rRNA-sequencing, and metabolites were examined and compared. The BB and BL groups showed improved liver histology and function based on liver/body ratios (WD 7.07 ± 0.75, BB 5.27 ± 0.47, and BL 4.86 ± 0.57) and NAFLD activity scores (WD 5.00 ± 0.10, BB 1.89 ± 1.45, and BL 1.90 ± 0.99; p < 0.05). Strain treatment showed ameliorative effects on gut barrier function. Metagenomic analysis showed treatment-specific changes in taxonomic composition. The community was mainly characterized by the significantly higher composition of the Bacteroidetes phylum among the NC and probiotic-feeding groups. Similarly, the gut metabolome was modulated by probiotics treatment. In particular, short-chain fatty acids and tryptophan metabolites were reverted to normal levels by probiotics, whereas bile acids were partially normalized to those of the NC group. The analysis of gene expression related to lipid and glucose metabolism as well as the immune response indicated the coordinative regulation of β-oxidation, lipogenesis, and systemic inflammation by probiotic treatment. BB and BL attenuate NAFLD by improving microbiome-associated factors of the gut-liver axis.

The gut microbiota has been known to modulate the immune responses in chronic liver diseases. Recent evidence suggests that effects of dietary foods on health care and human diseases are related to both the immune reaction and the microbiome. The gut-microbiome and intestinal immune system play a central role in the control of bacterial translocation-induced liver disease. Dysbiosis, small intestinal bacterial overgrowth, translocation, endotoxemia, and the direct effects of metabolites are the main events in the gut-liver axis, and immune responses act on every pathways of chronic liver disease. Microbiome-derived metabolites or bacteria themselves regulate immune cell functions such as recognition or activation of receptors, the control of gene expression by epigenetic change, activation of immune cells, and the integration of cellular metabolism. Here, we reviewed recent reports about the immunologic role of gut microbiotas in liver disease, highlighting the role of diet in chronic liver disease.