An Update on Animal Models of Alcohol-Associated Liver Disease

American Journal Of Pathology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

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Regulatory mechanisms of the probiotic-targeted gut–liver axis for the alleviation of alcohol-related liver disease: a review

Critical Reviews in Food Science and Nutrition, Год журнала: 2025, Номер unknown, С. 1 - 22

Опубликована: Фев. 5, 2025

Alcohol abuse-triggered alcohol-related liver disease (ALD) has become as a global public health concern that substantially affects the well-being and clinical status of patients. Although modern medicine provides various treatments for ALD, their effectiveness is limited can lead to adverse side effects. Probiotics have been employed prevent, alleviate, even treat with promising results. However, few comprehensive reviews are available on how they mitigate ALD by targeting gut-liver axis. This review systematically clarifies specific mediators axis in healthy states. It also describes alterations observed ALD. Furthermore, this thoroughly summarizes underlying mechanisms through which probiotics act relieve discusses current challenges faced research applications. Finally, we discuss future prospects using improves our understanding supports development application target therapeutic use.

Язык: Английский

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Gut cannabinoid receptor 1 regulates alcohol binge-induced intestinal permeability

eGastroenterology, Год журнала: 2025, Номер 3(1), С. e100173 - e100173

Опубликована: Фев. 1, 2025

Background Endocannabinoids acting via cannabinoid receptor 1 (CB1R) can elicit increased intestinal permeability (a condition also called ‘leaky gut’). Alcohol binge adversely affect digestive functions, including permeability; however, the underlying mechanisms remain incompletely understood. The current study aimed at examining whether CB1R is involved in alcohol binge-induced permeability. Methods We developed epithelial-specific knockout (CB1 IEC−/− ) mice and evaluated vivo contribution of gut Results anandamide levels proximal small intestine association with Radioligand binding functional assays confirmed that genetic deletion epithelial did not alter density or functionality brain. Additionally, a peripheral antagonist, ( S )-MRI-1891 (INV-202/monlunabant), exhibited comparable affinity to brain homogenates. An acute oral administration (3 mg/kg) reduced littermate control CB1 f/f floxed/floxed) but had no effect mice, underscoring role this phenomenon. Mechanistically, we found activated CB1R-ERK1/2 pathway subsequent downregulation tight junction proteins reduction villi length. In addition, targeting downstream ERK1/2 was able reverse process, upregulation length, thus improving barrier function. Despite effects on permeability, significantly metabolic parameters liver disease. Conclusion Our findings suggest promotes leaky activation demonstrate inhibition peripheral-restricted selective antagonists prevent

Язык: Английский

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Betaine regulates the gut-liver axis: a therapeutic approach for chronic liver diseases

Frontiers in Nutrition, Год журнала: 2025, Номер 12

Опубликована: Март 24, 2025

Chronic liver disease is defined by persistent harm to the that might result in decreased function. The two prevalent chronic diseases are alcohol-associated (ALD) and metabolic dysfunction-associated steatotic (MASLD). There ample evidence pathogenesis of these closely linked gastrointestinal dysfunctions alters gut-liver crosstalk. These alterations mediated through imbalances gut microbiota composition/function combined with disruption barrier integrity allows for harmful microbes their toxins enter portal circulation reach elicit an inflammatory response. This leads further recruitment systemic cells, such as neutrophils, T-cells, monocytes into liver, which perpetuate additional inflammation development progressive damage. Many therapeutic modalities, currently used prevent, attenuate, or treat aimed at modulating dysbiosis improving intestinal Betaine a choline-derived metabolite methyl group donor antioxidant, anti-inflammatory osmoprotectant properties. Studies have shown low betaine levels associated higher organ been several publications demonstrating role supplementation preventing ALD MASLD. review explores protective effects its capacity regulate maintain prevent diseases. Further studies needed enhance our understanding potential could pave way targeted interventions management not only diseases, but other bowel conditions.

Язык: Английский

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Lactiplantibacillus plantarum FRT4 protects against fatty liver hemorrhage syndrome: regulating gut microbiota and FoxO/TLR-4/NF-κB signaling pathway in laying hens

Microbiome, Год журнала: 2025, Номер 13(1)

Опубликована: Март 29, 2025

Fatty liver hemorrhage syndrome (FLHS) has become one of the major factors leading to death laying hen in caged egg production. FLHS is commonly associated with lipid peroxidation, hepatocyte injury, decreased antioxidant capacity, and inflammation. However, there are limited evidences regarding preventive effect Lactiplantibacillus plantarum on hens its mechanisms. Our previous results showed that Lp. FRT4 alleviated by regulating metabolism, but did not focus anti-inflammatory functions Therefore, this study aimed investigate mechanisms alleviating FLHS, a role activity inflammation regulation. Supplementation enhanced levels T-AOC, T-SOD, GSH-Px, while reducing TNF-α, IL-1β, IL-8, NLRP3 ovary hens. Additionally, upregulated mRNA expressions SOD1, SOD2, CAT, GPX1, downregulated pro-inflammatory IL-6, NLRP3, IL-4 IL-10. improved structure metabolic gut microbiota, regulated relative abundances dominant phyla (Bacteroidetes, Firmicute, Proteobacteria) genera (Prevotella Alistipes). it influenced key KEGG pathways, including tryptophan amino sugar nucleotide insulin signaling pathway, FoxO pathway. Spearman analysis revealed abundance microbiota at different taxonomic was closely related enzymes inflammatory factors. Furthermore, modulated FoxO/TLR-4/NF-κB pathway microbiota. Moreover, E2, FSH, VTG were significantly increased after intervention. effectively ameliorates This efficacy attributed properties, which mediated modulating function further intervening These actions enhance hepatic ovarian increase estrogen levels. Video Abstract.

Язык: Английский

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MetALD: New Perspectives on an Old Overlooked Disease

Liver International, Год журнала: 2025, Номер 45(5)

Опубликована: Апрель 3, 2025

ABSTRACT Metabolic dysfunction‐associated steatotic liver disease (MASLD) and alcohol‐associated (ALD) are the major contributors to burden globally. The rise in these conditions is linked obesity, type 2 diabetes, metabolic syndrome increased alcohol consumption. MASLD ALD share risk factors, pathophysiology histological features but differ their thresholds for use, definition does not require presence of dysfunction. A recent multi‐society consensus overhauled nomenclature steatosis introduced term MetALD describe patients with dysfunction who drink more than those less ALD. This new terminology aims enhance understanding management poses challenges, such as need accurately measure consumption research clinical practice settings. Recent studies show that has significant implications patient management, it associated mortality risks severe outcomes compared alone. face progression, cancer cardiovascular disease. diagnosis involves adequate quantification use through standardised questionnaires and/or biomarkers well proper assessment stage progression using non‐invasive tools including serologic markers, imaging, elastography techniques genetic testing. Effective requires addressing both alcohol‐related factors improve outcomes. review intends provide a comprehensive overview MetALD, covering pathogenesis, potential diagnostic approaches, strategies emerging therapies.

Язык: Английский

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Opposite regulation of intestinal and intrahepatic CD8⁺T cells controls alcohol-associated liver disease progression

Gut, Год журнала: 2025, Номер unknown, С. gutjnl - 334412

Опубликована: Апрель 8, 2025

Background Gut-liver crosstalk plays an important role in alcohol-associated liver disease (ALD) pathogenesis; but underlying mechanisms remain obscure. Objective We examined the regulation of intestinal and intrahepatic CD8 + T lymphocytes their contribution to ALD. Design ALD patients were recruited for evaluation cells. Single-cell RNA sequencing (scRNA seq) was performed analyse peripheral cells Wildtype, CD8-specific Bcl2 transgenic ( Cd8 Bcl-2 ), −/− mice subjected chronic-plus-binge ethanol feeding. Results In patients, duodenal selectively reduced negatively correlated with injury bacterial translocation markers, while markedly increased. ScRNA seq analysis patient livers revealed several populations expressing activation survival genes (eg, ). Transcriptomics functional studies a key prosurvival BCL2 this opposite Mechanistically, feeding specifically duodenum where levels are high. Inducing reversed ethanol-induced loss cells, improved gut barrier function ameliorated ALD, deficiency linked enhanced neutrophil macrophage infiltration liver, exacerbating mice. Conclusions is associated elevation which aggravates ameliorates respectively. Restoration functions may represent novel therapeutic strategy patients.

Язык: Английский

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Nanoparticle-based therapeutic strategies for chronic liver diseases: Advances and insights

Liver Research, Год журнала: 2025, Номер unknown

Опубликована: Апрель 1, 2025

Язык: Английский

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Toxicants as Risk Factors or Modifiers for Liver Disease

Elsevier eBooks, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

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Lipopolysaccharide, arbiter of the gut–liver axis, modulates hepatic cell pathophysiology in alcoholism

The Anatomical Record, Год журнала: 2024, Номер unknown

Опубликована: Авг. 21, 2024

Over the last four decades, clinical research and experimental studies have established that lipopolysaccharide (LPS)-a component of outer membrane gram-negative bacteria-is a potent hepatotoxic molecule in humans animals. Alcohol abuse is commonly associated with LPS endotoxemia. This review highlights molecular structures modes release from bacteria, plasma concentrations, induction microbiota dysbiosis, disruption gut epithelial barrier, translocation into portal circulation impacting pathophysiology hepatic cells via gut-liver axis. We describe illustrate vein its distributaries draining gastrointestinal tract. also elaborate on axis coupled enterohepatic represents bidirectional communication between liver. The updates data how circulating cleared coordinated effort Kupffer cells, hepatocytes, liver sinusoidal endothelial cells. Significantly, article reviews modes/mechanisms action by which mediates diverse stellate primarily association alcohol consumption. Specifically, we intricate linkages ethanol, production, axis, various maintenance barrier structural functional integrity microbiome homeostasis essential mitigating alcoholic disease improving health.

Язык: Английский

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