Interplay between gut microbiome, host genetic and epigenetic modifications in MASLD and MASLD-related hepatocellular carcinoma

Gut, Journal Year: 2024, Volume and Issue: 74(1), P. 141 - 152

Published: June 29, 2024

Metabolic dysfunction-associated steatotic liver disease (MASLD) encompasses a wide spectrum of injuries, ranging from hepatic steatosis, metabolic steatohepatitis (MASH), fibrosis, cirrhosis to MASLD-associated hepatocellular carcinoma (MASLD-HCC). Recent studies have highlighted the bidirectional impacts between host genetics/epigenetics and gut microbial community. Host genetics influence composition microbiome, while microbiota their derived metabolites can induce epigenetic modifications affect development MASLD. The exploration intricate relationship microbiome genetic/epigenetic makeup is anticipated yield promising avenues for therapeutic interventions targeting MASLD its associated conditions. In this review, we summarise effects alterations in MASLD-HCC. We further discuss research findings demonstrating genetics/epigenetics, emphasising significance interconnection prevention treatment.

Language: Английский

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NAFLD/MASLD and the Gut–Liver Axis: From Pathogenesis to Treatment Options

Metabolites, Journal Year: 2024, Volume and Issue: 14(7), P. 366 - 366

Published: June 28, 2024

Nonalcoholic fatty liver disease (NAFLD) poses an emerging threat topublic health. steatohepatitis (NASH) is reported to be the most rapidly rising cause of hepatocellular carcinoma in western world. Recently, a new term has been proposed: metabolic dysfunction-associated steatotic (MASLD). The introduction this terminology sparked debate about interchangeability these terms. pathogenesis NAFLD/MASLD thought multifactorial, involving both genetic and environmental factors. Among factors, alterations gut microbiota dysbiosis have recently garnered significant attention. In context, review will further discuss gut-liver axis, which refers bidirectional interaction between human liver. Additionally, therapeutic potential probiotics, particularly next-generation probiotics genetically engineered bacteria, explored. Moreover, role prebiotics, synbiotics, postbiotics, phages as well fecal transplantation analyzed. Particularly for lean patients with NAFLD/MASLD, who limited treatment options, approaches that modify diversity composition may hold promise. However, due ongoing safety concerns modulate microbiota, large-scale studies are necessary better assess their efficacy treating NAFLD/MASLD.

Language: Английский

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Gut Microbiome Modulation in Hepatocellular Carcinoma: Preventive Role in NAFLD/NASH Progression and Potential Applications in Immunotherapy-Based Strategies

Cells, Journal Year: 2025, Volume and Issue: 14(2), P. 84 - 84

Published: Jan. 9, 2025

Hepatocellular carcinoma (HCC) is a heterogeneous tumor associated with several risk factors, non-alcoholic fatty liver disease (NAFLD) emerging as an important cause of tumorigenesis. Due to the obesity epidemics, occurrence NAFLD has significantly increased nearly 30% prevalence worldwide. HCC often arises in background chronic (CLD), such nonalcoholic steatohepatitis (NASH) and cirrhosis. Gut microbiome (GM) alterations have been linked progression development, investigations reporting crucial role for gut-liver axis microbial metabolites promoting CLD. Moreover, GM affects homeostasis, energy status, immune microenvironment, influencing response immunotherapy interesting therapeutic implications. In this review, we summarize main changes derived (e.g., short-chain acids bile acids) occurring patients progression, emphasizing their potential early diagnostic biomarkers prognostic tools. We discuss weight loss effects diet-based interventions healthy lifestyles treatment patients, highlighting impact on restoration intestinal barrier structure. also describe encouraging preclinical findings modulation improve functions CLD, boost antitumor probiotic supplementations or anti-hypercholesterolemic drug treatment), ultimately delay HCC. The development safe effective strategies that target holds promise cancer prevention treatment, especially if personalized options will be considered.

Language: Английский

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Advances in Fecal Microbiota Transplantation for Gut Dysbiosis‐Related Diseases

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 27, 2025

Abstract This article provides an overview of the advancements in application fecal microbiota transplantation (FMT) treating diseases related to intestinal dysbiosis. FMT involves transfer healthy donor into patient's body, aiming restore balance and thereby treat a variety such as recurrent Clostridioides difficile infection (rCDI), inflammatory bowel disease (IBD), constipation, short syndrome (SBS), irritable (IBS). While has shown high efficacy treatment rCDI, further research is needed for its other chronic conditions. elaborates on mechanisms dysbiosis, well discusses key factors influencing effectiveness FMT, including selection, recipient characteristics, protocols, methods assessing microbiota. Additionally, it emphasizes successful FMT. Future should focus optimizing process ensure long‐term safety explore potential broader range medical

Language: Английский

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Multidimensional Interactive Cascading Nanochips for Detection of Multiple Liver Diseases via Precise Metabolite Profiling

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(21)

Published: Jan. 24, 2024

Abstract It is challenging to detect and differentiate multiple diseases with high complexity/similarity from the same organ. Metabolic analysis based on nanomatrix‐assisted laser desorption/ionization mass spectrometry (NMALDI‐MS) a promising platform for disease diagnosis, while enhanced property of its core nanomatrix materials has plenty room improvement. Herein, multidimensional interactive cascade nanochip composed iron oxide nanoparticles (FeNPs)/MXene/gold (AuNPs), IMG, reported serum metabolic profiling achieve high‐throughput detection liver diseases. MXene serves as multi‐binding site an electron‐hole source ionization during NMALDI‐MS analysis. Introduction AuNPs surface plasmon resonance (SPR) properties facilitates charge accumulation rapid energy conversion. FeNPs are integrated into MXene/Au nanocomposite sharply reduce thermal conductivity negligible heat loss strong thermally‐driven desorption, construct multi‐interaction proton transport pathway ionization. Analysis these fingerprint signals detected IMG through neural network model results in differentiation via single pass revelation potential biomarkers. The method can rapidly accurately screen various diseases, thus allowing timely treatment

Language: Английский

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The Gut Microbial Regulation of Epigenetic Modification from a Metabolic Perspective

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(13), P. 7175 - 7175

Published: June 29, 2024

Obesity is a global health challenge that has received increasing attention in contemporary research. The gut microbiota been implicated the development of obesity, primarily through its involvement regulating various host metabolic processes. Recent research suggests epigenetic modifications may serve as crucial pathways which and metabolites contribute to pathogenesis obesity other disorders. Hence, understanding interplay between mechanisms for elucidating impact on host. This review focuses relationship with several obesity-related pathogenic mechanisms, including energy dysregulation, inflammation, maternal inheritance. These findings could novel therapeutic targets probiotics, prebiotics, fecal transplantation tools treating disruptions. It also aid developing strategies modulate microbiota, thereby characteristics obesity.

Language: Английский

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Immunological mechanisms in steatotic liver diseases: An overview and clinical perspectives

Clinical and Molecular Hepatology, Journal Year: 2024, Volume and Issue: 30(4), P. 620 - 648

Published: July 11, 2024

Steatotic liver diseases (SLD) are the principal worldwide cause of cirrhosis and end-stage cancer, affecting nearly a quarter global population. SLD includes metabolic dysfunction-associated alcoholic disease (MetALD) steatotic (MASLD), resulting in asymptomatic steatosis, fibrosis, associated complications. The immune processes include gut dysbiosis, adiposeliver organ crosstalk, hepatocyte death cell-mediated inflammatory processes. Notably, various cells such as B cells, plasma dendritic conventional CD4⁺ CD8⁺ T innate-like platelets, neutrophils macrophages play vital roles development MetALD MASLD. Immunological modulations targeting death, reactions microbiome N-acetylcysteine, selonsertib, F-652, prednisone, pentoxifylline, anakinra, JKB-121, HA35, obeticholic acid, probiotics, prebiotics, antibiotics fecal microbiota transplantation. Understanding immunological mechanisms underlying is crucial for advancing clinical therapeutic strategies.

Language: Английский

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Machine-learning assisted discovery unveils novel interplay between gut microbiota and host metabolic disturbance in diabetic kidney disease

Gut Microbes, Journal Year: 2025, Volume and Issue: 17(1)

Published: March 6, 2025

Diabetic kidney disease (DKD) is a serious healthcare dilemma. Nonetheless, the interplay between functional capacity of gut microbiota and their host remains elusive for DKD. This study aims to elucidate capability affect function DKD patients. A total 990 subjects were enrolled consisting control group (n = 455), type 2 diabetes mellitus (DM, n 204), 182) chronic (CKD, 149). Full-length sequencing 16S rRNA genes from stool DNA was conducted. Three findings are pinpointed. Firstly, new types biomarkers have been created using machine-learning (ML) method, namely relative abundance microbe, presence or absence hierarchy ratio two different taxonomies. Four panels features selected be analyzed: (i) DM vs. Control, (ii) DM, (iii) CKD, (iv) CKD Control. These had accuracy rates 0.72 0.78 areas under curve 0.79 0.86. Secondly, 13 biomarkers, which strongly correlated with anthropometric, metabolic and/or renal indexes, concomitantly identified by ML algorithm differential method highly discriminatory. Finally, predicted DKD-specific biomarker, Gemmiger spp. enriched in carbohydrate metabolism branched-chain amino acid (BCAA) biosynthesis. Coincidentally, circulating levels various BCAAs (L-valine, L-leucine L-isoleucine) precursor, L-glutamate, significantly increased patients, suggests that, when hyperglycemia present, there has alterations interconnected pathways associated glycolysis, pyruvate fermentation BCAA Our demonstrate that link involving gut-kidney axis Furthermore, our highlight specific bacteria can acts as useful biomarkers; these could mechanistic diagnostic implications.

Language: Английский

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Gut Microbiota Dysbiosis: Pathogenesis, Diseases, Prevention, and Therapy

MedComm, Journal Year: 2025, Volume and Issue: 6(5)

Published: April 18, 2025

ABSTRACT Dysbiosis refers to the disruption of gut microbiota balance and is pathological basis various diseases. The main pathogenic mechanisms include impaired intestinal mucosal barrier function, inflammation activation, immune dysregulation, metabolic abnormalities. These involve dysfunctions in gut–brain axis, gut–liver others cause broader effects. Although association between diseases caused by dysbiosis has been extensively studied, many questions remain regarding specific treatment strategies. This review begins examining causes summarizes potential representative imbalance. It integrates clinical evidence explore preventive therapeutic strategies targeting emphasizing importance understanding dysbiosis. Finally, we summarized development artificial intelligence (AI) research suggested that it will play a critical role future studies on combining multiomics technologies AI further uncover complex drive personalized

Language: Английский

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The role of the microbiome in liver disease

Current Opinion in Gastroenterology, Journal Year: 2024, Volume and Issue: 40(3), P. 134 - 142

Published: Feb. 16, 2024

Purpose of review The intestinal microbiome and the gut-liver axis play a major role in health disease. human gut harbors trillions microbes disruption homeostasis can contribute to liver In this review, progress field within last 3 years is summarized, focusing on metabolic dysfunction-associated steatotic disease (MASLD), alcohol-associated (ALD), autoimmune (AILD), hepatocellular carcinoma (HCC). Recent findings Changes fecal virome fungal mycobiome have been described patients with various diseases. Several microbial derived metabolites including endogenous ethanol produced by bacteria, mechanistically linked such as MASLD. Virulence factors encoded bacteria ALD, AILD HCC. Novel therapeutic approaches focused phages, pre- postbiotics successfully used preclinical models. Fecal microbiota transplantation has effective attenuating Probiotics are safe hepatitis improve alcohol addiction. Summary gut–liver plays key pathophysiology Understanding help develop precise centered therapies.

Language: Английский

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