The Potential Benefits of Akkermansia muciniphila as a Next-Generation Probiotic in the Maintenance of Overall Liver Health.

When specific gut microbes reveal a possible link between hepatic steatosis and adipose tissue

The role of the gut microbiome in chronic liver disease: the clinical evidence revised.

Silencing a Killer Among Us: Ethanol Impairs Immune Surveillance of Activated Stellate Cells by Natural Killer Cells

The Gut Microbiome in Health and Disease

Gut microbiota lends a helping hand to nurse liver regeneration

Human Immunodeficiency Virus-Related Microbial Translocation and Progression of Hepatitis C

Targeting the Gut Microbiota in Coronavirus Disease 2019: Hype or Hope?

Simple SummaryThe gut microbiome plays a crucial role in regulating metabolism, inflammation, and immunological pathways. Increasing evidence shows that the microbial ecosystem can also influence many hepatological conditions through the gut–liver axis, shaping disease development, progression, and response to treatment. Akkermansia muciniphila is one of the rising stars of this ecosystem, playing a key role in maintaining intestinal integrity and promoting immune activation. Its presence may also improve the efficacy of antitumoral systemic therapy, including immunotherapy for hepatocellular carcinoma. Although current data come from preclinical and small clinical studies, these insights highlight a promising frontier where microbiome modulation could complement oncological treatments and improve outcomes for patients with liver cancer. In this review, we discuss the biological pathways regulated by the gut microbiome, particularly those involving Akkermansia muciniphila, their relevance in the development of liver cancer, and how they could be linked to the modulation of immunotherapy response.Immune checkpoint inhibitors (ICIs) have radically changed the landscape of systemic treatment for hepatocellular carcinoma (HCC). Recently, there has been increasing interest regarding the relationship between the gut microbiome and the response to immunotherapy in oncological treatments. Among the gut commensals, Akkermansia (A.) muciniphila has gained increasing attention in the literature. A. muciniphila may affect the tumor microenvironment and enhance the efficacy of systemic therapies, including ICIs and targeted agents, by shaping host immune responses and metabolic pathways. This narrative review summarizes the current knowledge on A. muciniphila and its potential interaction with systemic therapies for HCC, focusing on its immunostimulatory properties, including enhancement of cytotoxic CD8+ T-cell activity and reversal of immunosuppressive tumor microenvironments. The therapeutic role of A. muciniphila might represent a novel and promising weapon in the HCC field, although the road is still long and the scientific evidence still remains in an exploratory stage. Its integration into clinical practice, however, requires robust clinical trials and a deeper understanding of its interactions within the gut–liver axis and tumor ecosystem.

Recent research has highlighted the complex relationship between gut microbiota, metabolic pathways, and nonalcoholic fatty liver disease (NAFLD) progression. Gut dysbiosis, commonly observed in NAFLD patients, impairs intestinal permeability, leading to the translocation of bacterial products like lipopolysaccharides, short-chain fatty acids, and ethanol to the liver. These microbiome-associated mechanisms contribute to intestinal and hepatic inflammation, potentially advancing NAFLD to NASH. Dietary habits, particularly those rich in saturated fats and fructose, can modify the microbiome composition, leading to dysbiosis and fatty liver development. Metabolomic approaches have identified unique profiles in NASH patients, with specific metabolites like ethanol linked to disease progression. While bariatric surgery has shown promise in preventing NAFLD progression, the role of gut microbiome and metabolites in this improvement remains to be proven. Understanding these microbiome-related pathways may provide new diagnostic and therapeutic targets for NAFLD and NASH. A comprehensive review of current literature was conducted using multiple medical research databases, including PubMed, Scopus, Web of Science, Embase, Cochrane Library, ClinicalTrials.gov, ScienceDirect, Medline, ProQuest, and Google Scholar. The review focused on studies that examine the relationship between gut microbiota composition, metabolic pathways, and NAFLD progression. Key areas of interest included microbial dysbiosis, endotoxin production, and the influence of diet on gut microbiota. The analysis revealed that gut dysbiosis contributes to NAFLD through several mechanisms, diet significantly influences gut microbiota composition, which in turn affects liver function through the gut-liver axis. High-fat diets can lead to dysbiosis, altering microbial metabolic activities and promoting liver inflammation. Specifically, gut microbiota-mediated generation of saturated fatty acids, such as palmitic acid, can activate liver macrophages and increase TNF-α expression, contributing to NASH development. Different dietary components, including cholesterol, fiber, fat, and carbohydrates, can modulate the gut microbiome and influence NAFLD progression. This gut-liver axis plays a crucial role in maintaining immune homeostasis, with the liver responding to gut-derived bacteria by activating innate and adaptive immune responses. Microbial metabolites, such as bile acids, tryptophan catabolites, and branched-chain amino acids, regulate adipose tissue and intestinal homeostasis, contributing to NASH pathogenesis. Additionally, the microbiome of NASH patients shows an elevated capacity for alcohol production, suggesting similarities between alcoholic steatohepatitis and NASH. These findings indicate that targeting the gut microbiota may be a promising approach for NASH treatment and prevention. Recent research highlights the potential of targeting gut microbiota for managing nonalcoholic fatty liver disease (NAFLD). The gut-liver axis plays a crucial role in NAFLD pathophysiology, with dysbiosis contributing to disease progression. Various therapeutic approaches aimed at modulating gut microbiota have shown promise, including probiotics, prebiotics, synbiotics, fecal microbiota transplantation, and dietary interventions. Probiotics have demonstrated efficacy in human randomized controlled trials, while other interventions require further investigation in clinical settings. These microbiota-targeted therapies may improve NAFLD outcomes through multiple mechanisms, such as reducing inflammation and enhancing metabolic function. Although lifestyle modifications remain the primary recommendation for NAFLD management, microbiota-focused interventions offer a promising alternative for patients struggling to achieve weight loss targets.

Gut microbial dysbiosis associates hepatocellular carcinoma via the gut-liver axis

Gut microbiota constitute a complicated but manifold ecosystem, in which specific symbiotic relationships are formed among various bacteria. To maintain a steady state, the gastrointestinal tract and the liver form a close anatomical and functional two-way, interconnected network through the portal circulation. "Gut-liver axis" plays a key role in the pathogenesis of liver diseases. Accumulating evidence indicates that gut microbiota can influence the liver pathophysiology directly or indirectly via a variety of signal pathways. In a pathological state where an ecological imbalance occurs at the compositional and functional levels, gut microbes would interact with the host immune system and other type of cells to cause liver steatosis, inflammation and fibrosis, which in turn give rise to the development of such liver diseases as alcoholic liver disease, nonalcoholic fatty liver disease, primary sclerosing cholangitis, and acute liver failure, to name a few. Studies have shown that microorganisms, such as prebiotics and probiotics, can improve the prognosis of certain diseases, which open a new era of treating liver diseases with bacteria. There are many unknowns and hidden values in the gut microbiome. To explore the pathophysiological mechanism of various complex diseases and develop scientific and effective clinical treatment strategies, efforts should be made to obtain insights into how certain intestinal microbiota participates in the occurrence and progression of liver diseases. As the connection between gut microbiota and liver diseases at both the acute and chronic phases was not elaborated in previously published review articles, herein we discuss the association between gut microbiota and both acute and chronic liver injury. The anatomical structure of the liver enables it to form a close network with the gut microbiota, which is an important mediator in the regulation of the hepatic physiological and pathological functions.

Distinct alterations of gut morphology and microbiota characterize accelerated diabetes onset in nonobese diabetic mice

S-adenosylmethionine (SAMe) therapy in liver disease: A review of current evidence and clinical utility

Inflammation: The Straw That Broke the NAFLD Liver!

Non alcoholic fatty liver disease (NAFLD), as an increasingly serious global public health problem, has become the largest chronic liver disease in China, with a global incidence rate of about 25%, and is increasing year by year. disease in China, with a global incidence rate of about 25%, and is increasing year by year. As an important disease in the liver, an increasing number of studies have confirmed the significant role of gut microbiota and its metabolites in the progression of non-alcoholic fatty liver disease. There is a close structural and functional relationship between the gut microbiota and its metabolites in the liver. There is a close structural and functional relationship between the gut and liver due to the "gut liver axis". The gut microbiota and its metabolites, such as abnormal metabolism of bile acids (TBA), trimethylamine oxide (TMAO), lipopolysaccharides (LPS), short chain fatty acids (SCFAs), and other metabolites in the progression of non-alcoholic fatty liver disease. short chain fatty acids (SCFAs), tryptophan (Trp), etc., can restrict and regulate the use of host cells by binding to corresponding receptor activated signaling pathways, thereby participating in the occurrence and development of NAFLD and affecting the process of non-alcoholic fatty liver disease. Studies have shown that probiotics can be used to regulate the gut microbiota to promote the treatment of NAFLD. This article mainly studies the relationship and mechanism between gut microbiota and NAFLD. relationship and mechanism between gut microbiota and related metabolites and the pathogenesis of NAFLD, providing new ideas for the prevention, delay NAFLD, providing new ideas for the prevention, delay, and treatment of NAFLD.