Betaine regulates the gut-liver axis: a therapeutic approach for chronic liver diseases DOI Creative Commons
Sathish Kumar Perumal, Madan Kumar Arumugam, Natalia A. Osna

et al.

Frontiers in Nutrition, Journal Year: 2025, Volume and Issue: 12

Published: March 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.

Language: Английский

Alcohol-associated liver disease DOI Creative Commons
Bryan Mackowiak, Yaojie Fu, Luca Maccioni

et al.

Journal of Clinical Investigation, Journal Year: 2024, Volume and Issue: 134(3)

Published: Feb. 1, 2024

Alcohol-associated liver disease (ALD) is a major cause of chronic worldwide, and comprises spectrum several different disorders, including simple steatosis, steatohepatitis, cirrhosis, superimposed hepatocellular carcinoma. Although tremendous progress has been made in the field ALD over last 20 years, pathogenesis remains obscure, there are currently no FDA-approved drugs for treatment ALD. In this Review, we discuss new insights into therapeutic targets ALD, utilizing study multiomics other cutting-edge approaches. The potential translation these studies clinical practice therapy deliberated. We also preclinical models interplay metabolic dysfunction, alcohol-associated cancer, heterogeneity some translational research prospects

Language: Английский

Citations

130
The intersection between alcohol-related liver disease and nonalcoholic fatty liver disease DOI
Luis Antonio Díaz, Juan Pablo Arab, Alexandre Louvet

et al.

Nature Reviews Gastroenterology & Hepatology, Journal Year: 2023, Volume and Issue: 20(12), P. 764 - 783

Published: Aug. 15, 2023

Language: Английский

Citations

103
Liver diseases: epidemiology, causes, trends and predictions DOI Creative Commons

Can Gan,

Yuan Yuan, Haiyuan Shen

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: Feb. 4, 2025

Abstract As a highly complex organ with digestive, endocrine, and immune-regulatory functions, the liver is pivotal in maintaining physiological homeostasis through its roles metabolism, detoxification, immune response. Various factors including viruses, alcohol, metabolites, toxins, other pathogenic agents can compromise function, leading to acute or chronic injury that may progress end-stage diseases. While sharing common features, diseases exhibit distinct pathophysiological, clinical, therapeutic profiles. Currently, contribute approximately 2 million deaths globally each year, imposing significant economic social burdens worldwide. However, there no cure for many kinds of diseases, partly due lack thorough understanding development these Therefore, this review provides comprehensive examination epidemiology characteristics covering spectrum from conditions manifestations. We also highlight multifaceted mechanisms underlying initiation progression spanning molecular cellular levels networks. Additionally, offers updates on innovative diagnostic techniques, current treatments, potential targets presently under clinical evaluation. Recent advances pathogenesis hold critical implications translational value novel strategies.

Language: Английский

Citations

9
Regulatory mechanisms of the probiotic-targeted gut–liver axis for the alleviation of alcohol-related liver disease: a review DOI

Feiyu Yang,

Xiangfei Li, Jing Sun

et al.

Critical Reviews in Food Science and Nutrition, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 22

Published: Feb. 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.

Language: Английский

Citations

3
Fibrosis: cross-organ biology and pathways to development of innovative drugs DOI
Florian Rieder, Laura E. Nagy, Toby M. Maher

et al.

Nature Reviews Drug Discovery, Journal Year: 2025, Volume and Issue: unknown

Published: March 18, 2025

Language: Английский

Citations

3
Gut-liver axis: Recent concepts in pathophysiology in alcohol-associated liver disease DOI
Fernanda Raya Tonetti, Álvaro Eguileor, Marko Mrdjen

et al.

Hepatology, Journal Year: 2024, Volume and Issue: 80(6), P. 1342 - 1371

Published: May 1, 2024

The growing recognition of the role gut microbiome’s impact on alcohol-associated diseases, especially in liver disease, emphasizes need to understand molecular mechanisms involved governing organ-organ communication identify novel avenues combat diseases. gut-liver axis refers bidirectional and interaction between liver. Intestinal microbiota plays a pivotal maintaining homeostasis within axis, this significant disease. intricate intestine involves multiple cellular components each organ that enable them carry out their physiological functions. In review, we focus approaches understanding how chronic alcohol exposure impacts microbiome individual cells intestine, as well ethanol machinery required for intraorgan interorgan communication.

Language: Английский

Citations

17
Effects of elafibranor on liver fibrosis and gut barrier function in a mouse model of alcohol-associated liver disease DOI

Aritoshi Koizumi,

Kosuke Kaji, Norihisa Nishimura

et al.

World Journal of Gastroenterology, Journal Year: 2024, Volume and Issue: 30(28), P. 3428 - 3446

Published: July 24, 2024

BACKGROUND Alcohol-associated liver disease (ALD) is a leading cause of liver-related morbidity and mortality, but there are no therapeutic targets modalities to prevent ALD-related fibrosis. Peroxisome proliferator activated receptor (PPAR) α δ play key role in lipid metabolism intestinal barrier homeostasis, which major contributors the pathological progression ALD. Meanwhile, elafibranor (EFN), dual PPARα PPARδ agonist, has reached phase III clinical trial for treatment metabolic dysfunction-associated steatotic primary biliary cholangitis. However, benefits EFN ALD unknown. AIM To evaluate inhibitory effects on fibrosis gut-intestinal dysfunction an mouse model. METHODS was induced female C57BL/6J mice by feeding 2.5% ethanol (EtOH)-containing Lieber-DeCarli liquid diet intraperitoneally injecting carbon tetrachloride thrice weekly (1 mL/kg) 8 weeks. (3 10 mg/kg/day) orally administered during experimental period. Histological molecular analyses were performed assess effect steatohepatitis, fibrosis, integrity. The HepG2 lipotoxicity Caco-2 function evaluated cell-based assays. RESULTS hepatic steatosis, apoptosis, model significantly attenuated treatment. promoted lipolysis β-oxidation enhanced autophagic antioxidant capacities EtOH-stimulated cells, primarily through activation. Moreover, inhibited Kupffer cell-mediated inflammatory response, with blunted exposure lipopolysaccharide (LPS) toll like 4 (TLR4)/nuclear factor kappa B (NF-κB) signaling. improved hyperpermeability restoring tight junction proteins autophagy inhibiting apoptosis proinflammatory responses. protective cells predominantly mediated CONCLUSION reduced accumulation enhancing hepatocyte capacities, suppressing LPS/TLR4/NF-κB-mediated responses function.

Language: Английский

Citations

15
Inflammation in Alcohol-Associated Hepatitis: Pathogenesis and Therapeutic Targets DOI Creative Commons
Dechun Feng, Seonghwan Hwang, Adrien Guillot

et al.

Cellular and Molecular Gastroenterology and Hepatology, Journal Year: 2024, Volume and Issue: 18(3), P. 101352 - 101352

Published: Jan. 1, 2024

Alcohol-associated hepatitis (AH) is an acute-on-chronic liver injury that occurs in patients with chronic alcohol-associated disease (ALD). Patients severe AH have high short-term mortality and lack effective pharmacologic therapies. Inflammation believed to be one of the key factors promoting progression has been actively investigated as therapeutic targets over last several decades, but no inflammatory identified so far. In this review, we discuss how cells mediators produced by these contribute development AH, focus on neutrophils macrophages. The crosstalk between nonparenchymal pathogenesis elaborated. We also deliberate application recent cutting-edge technologies characterizing inflammation AH. Finally, potential for are briefly summarized.

Language: Английский

Citations

13
Solanum nigrum L. berries extract ameliorated the alcoholic liver injury by regulating gut microbiota, lipid metabolism, inflammation, and oxidative stress DOI

Xueying Wang,

Ziqi Sun,

Xiaoli Wang

et al.

Food Research International, Journal Year: 2024, Volume and Issue: 188, P. 114489 - 114489

Published: May 9, 2024

Language: Английский

Citations

13
Oxidative stress in alcoholic liver disease, focusing on proteins, nucleic acids, and lipids: A review DOI

Weiwen Lai,

Jiahua Zhang,

Jiawei Sun

et al.

International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: 278, P. 134809 - 134809

Published: Aug. 16, 2024

Language: Английский

Citations

13