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The metabolites of gut microbiota show favorable therapeutic effects on nonalcoholic fatty liver disease (NAFLD), but the active metabolites and mechanisms against NAFLD have not been documented. The aim of the study was to investigate the active metabolites and mechanisms of gut microbiota against NAFLD by network pharmacology. We obtained a total of 208 metabolites from the gutMgene database and retrieved 1256 targets from similarity ensemble approach (SEA) and 947 targets from the SwissTargetPrediction (STP) database. In the SEA and STP databases, we identified 668 overlapping targets and obtained 237 targets for NAFLD. Thirty-eight targets were identified out of those 237 and 223 targets retrieved from the gutMgene database, and were considered the final NAFLD targets of metabolites from the microbiome. The results of molecular docking tests suggest that, of the 38 targets, mitogen-activated protein kinase 8-compound K and glycogen synthase kinase-3 beta-myricetin complexes might inhibit the Wnt signaling pathway. The microbiota-signaling pathways-targets-metabolites network analysis reveals that Firmicutes, Fusobacteria, the Toll-like receptor signaling pathway, mitogen-activated protein kinase 1, and phenylacetylglutamine are notable components of NAFLD and therefore to understanding its processes and possible therapeutic approaches. The key components and potential mechanisms of metabolites from gut microbiota against NAFLD were explored utilizing network pharmacology analyses. This study provides scientific evidence to support the therapeutic efficacy of metabolites for NAFLD and suggests holistic insights on which to base further research.

We intended to identify favourable metabolite(s) and pharmacological mechanism(s) of gut microbiota (GM) for liver regeneration (LR) through network pharmacology. We utilized the gutMGene database to obtain metabolites of GM, and targets associated with metabolites as well as LR-related targets were identified using public databases. Furthermore, we performed a molecular docking assay on the active metabolite(s) and target(s) to verify the network pharmacological concept. We mined a total of 208 metabolites in the gutMGene database and selected 668 targets from the SEA (1,256 targets) and STP (947 targets) databases. Finally, 13 targets were identified between 61 targets and the gutMGene database (243 targets). Protein-protein interaction network analysis showed that AKT1 is a hub target correlated with 12 additional targets. In this study, we describe the potential microbe from the microbiota (

Non-alcoholic fatty liver disease (NAFLD) is an initial etiology to be developed steatosis, liver fibrosis, cirrhosis, and even hepatocellular carcinoma. However, the noticeable therapeutics were not elucidated completely to dampen the progressive rate involved in NAFLD. In the incomplete project, we combined secondary metabolites (SMs) from gut microbiota (GM) and Hordeum vulgare (HV) as a representative grain with potent NAFLD to exert combinatorial effects via network pharmacology. Hence, we retrieved the SMs of HV from NPASS (Natural product Activity & Species Source Database) and SMs of GM from gutMGene database. Then, targets associated with SMs were identified from both SEA (Similarity Ensemble Approach) and STP (SwissTargetPrediction). The crucial overlapping targets were identified on NAFLD-related targets through Ven diagram plotter. We constructed the protein-protein interaction (PPI) network from the crucial targets and built a bubble plot to identify a key mechanism on NAFLD. Also, we analyzed microbiota or barley – signaling pathways – targets – metabolites (MBSTM) in aspects of combinatorial approach (HV, and GM). To be confirmed a significant SM against NAFLD, we performed Molecular Docking (MD) with Autodock 1.5.6 to verify the affinity between SMs and targets. Finally, drug-likeness and toxicity properties of key SMs were validated via SwissADME and ADMETlab platform. The number of 31 core targets was analyzed by PPI network, the result of which represented JUN as a key target on NAFLD. The key SM bound stably to JUN were Tryptanthrin from HV. On a bubble plot, we identified that Apelin signaling pathway might be an inhibitive mechanism to relieve NAFLD in the combinatorial approach. On the holistic viewpoints, we analyzed MBSTM to obtain components associated with Apelin signaling pathway. As a result, we found the primary GM to fight NAFLD: Microbiota (Eubacterium limosum; Eggerthella sp. SDG-2; Alistipes indistinctus YIT 12060; Odoribacter laneus YIT 12061; Paraprevotella clara YIT 11840; Paraprevotella xylaniphila YIT 11841). The MD provided what the key SM (Dihydroglycitein, 1,3-Diphenylpropan-2-ol, and Acetic) is on each target (HDAC5, NOS1, and NOS2) related directly to Apelin signaling pathway. Overall, these results suggest that combinatorial application could be an effective tactic for ameliorating NAFLD.

Background Nonalcoholic fatty liver disease (NAFLD) has been issued in a wide range of complicated progressive interruption such as steatosis, fibrosis, cirrhosis, and even hepatocellular carcinoma. However, a key therapy to unravel the progressive diseases associated with NAFLD has not been established completely among taking many of the potential compounds. In the context of the unfinished project, we comprised metabolites of gut microbiota (endogenous species) and dietary plant-derived natural flavonoids (exogenous species) known as potent antioxidant, antiinflammation, and anticancer, in search for combinatorial effects via network pharmacology analysis. Results We identified the 668 overlapping targets related to metabolites from gut microbiota between SEA and STP; and we selected 14 out of 16 flavonoids because the 2 flavonoids were violated by Lipinski’s rule. The flavonoids’ targets were 112, compared with the 668 overlapping targets to identify the significant targets. Then, we identified the final 47 intersecting targets against NAFLD. On PPI networks, both VEGFA and AKT1 had the highest degree value, which were considered as hub targets against NAFLD. In bubble chart, cAMP signaling pathway was a key mode to be functioned as inhibitive mechanism. On the networks of microbiota (or natural products)-metabolites-targets-key signaling pathway, Enterococcus sp. 45, Escherichia sp.12, Escherichia sp.33, and Bacterium MRG-PMF-1 as key microbiota; flavonoid-rich products as key natural resources; luteolin, and myricetin as key metabolites (or dietary flavonoids); CFTR, PIK3R1, and AKT1 as key targets are potential key components to treat NAFLD, by suppressing cAMP signaling pathway. Conclusion In this study, we suggested that four components (microbiota, metabolites, targets, and a key signaling pathway) and dietary plant-derived natural flavonoids can be exerted combinatorial pharmacological effects against NAFLD.

Background: The metabolites of gut microbiota show favorable therapeutic effects on nonalcoholic fatty liver disease (NAFLD), but the active metabolites and mechanisms against NAFLD have not been documented. The aim of the study was to investigate the active metabolites and mechanisms of gut microbiota against NAFLD by network pharmacology. Results: We obtained a total of 208 metabolites from the gutMgene database and retrieved 1,256 targets from similarity ensemble approach (SEA) and 947 targets from the SwissTargetPrediction (STP) database. In the SEA and STP databases, we identified 668 overlapping targets and obtained 237 targets for NAFLD. Thirty-eight targets were identified out of those 237 and 223 targets retrieved from the gutMgene database, and were considered the final NAFLD targets of metabolites from the microbiome. The results of molecular docking tests suggest that, of the 38 targets, mitogen-activated protein kinase 8-compound K and glycogen synthase kinase-3 beta-myricetin complexes might inhibit the Wnt signaling pathway. The microbiota-signaling pathways-targets-metabolites network analysis reveals that Firmicutes, Fusobacteria, the Toll-like receptor signaling pathway, mitogen-activated protein kinase 1, and phenylacetylglutamine are notable components of NAFLD.Conclusion: The key components and potential mechanisms of metabolites from gut microbiota against NAFLD were explored utilizing network pharmacology analyses. This study provides scientific evidence to support the therapeutic efficacy of metabolites for NAFLD and suggests holistic insights for further research.

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.

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

A novel high refractive index hybrid film was produced by hybridization of carbazole phenoxy based copolymers and titania. The random copolymer was prepared first by copolymerization of carbazole p...

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.

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.