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

Gut, Год журнала: 2024, Номер 74(1), С. 141 - 152

Опубликована: Июнь 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.

Язык: Английский

---

Understanding gut dysbiosis for hepatocellular carcinoma diagnosis and treatment

Trends in Endocrinology and Metabolism, Год журнала: 2024, Номер 35(11), С. 1006 - 1020

Опубликована: Июль 5, 2024

The gut microbiome can play a crucial role in hepatocellular carcinoma (HCC) progression through the enterohepatic circulation, primarily acting via metabolic reprogramming and alterations hepatic immune microenvironment triggered by microbe-associated molecular patterns (MAMPs), metabolites, fungi. In addition, shows potential as biomarker for early HCC diagnosis assessing efficacy of immunotherapy unresectable HCC. This review examines how microbiota dysbiosis, with varied functional profiles, contributes to HCCs different etiologies. We discuss therapeutic strategies modulate including diets, antibiotics, probiotics, fecal transplantation, nano-delivery systems, underscore their an adjunctive treatment modality

Язык: Английский

---

Probiotics and Non-Alcoholic Fatty Liver Disease: Unveiling the Mechanisms of Lactobacillus plantarum and Bifidobacterium bifidum in Modulating Lipid Metabolism, Inflammation, and Intestinal Barrier Integrity

Foods, Год журнала: 2024, Номер 13(18), С. 2992 - 2992

Опубликована: Сен. 21, 2024

In recent years, the prevalence of non-alcoholic fatty liver disease (NAFLD) has risen annually, yet due to intricacies its pathogenesis and therapeutic challenges, there remains no definitive medication for this condition. This review explores intricate relationship between intestinal microbiome NAFLD, emphasizing substantial roles played by

Язык: Английский

---

Short-chain fatty acids and cancer

Trends in cancer, Год журнала: 2024, Номер unknown

Опубликована: Дек. 1, 2024

Язык: Английский

---

Organoids and spheroids: advanced in vitro models for liver cancer research

Frontiers in Cell and Developmental Biology, Год журнала: 2025, Номер 12

Опубликована: Янв. 9, 2025

Liver cancer is a leading cause of cancer-related deaths worldwide, highlighting the need for innovative approaches to understand its complex biology and develop effective treatments. While traditional in vivo animal models have played vital role liver research, ethical concerns demand more human-relevant systems driven development advanced vitro models. Spheroids organoids emerged as powerful tools due their ability replicate tumor microenvironment facilitate preclinical drug development. are simpler 3D culture that partially recreate structure cell interactions. They can be used penetration studies high-throughput screening. Organoids derived from stem cells or patient tissues accurately emulate complexity functionality tissue. generated pluripotent adult cells, well specimens, providing personalized studying behavior responses. retain genetic variability original offer robust platform screening treatment strategies. However, both spheroids limitations, such absence functional vasculature immune components, which essential growth therapeutic The field modeling evolving, with ongoing efforts predictive reflect complexities human cancer. By integrating these tools, researchers gain deeper insights into accelerate novel

Язык: Английский

---

Pharmacological treatment for metabolic dysfunction–associated steatotic liver disease and related disorders: Current and emerging therapeutic options

Pharmacological Reviews, Год журнала: 2025, Номер 77(2), С. 100018 - 100018

Опубликована: Янв. 7, 2025

Metabolic dysfunction-associated steatotic liver disease (MASLD; formerly known as nonalcoholic fatty disease) is a chronic affecting over billion individuals worldwide. MASLD can gradually develop into more severe pathologies, including metabolic steatohepatitis (MASH), cirrhosis, and malignancy. Notably, although being global health problem, there are very limited therapeutic options against its related diseases. While thyroid hormone receptor agonist (resmetirom) recently approved for MASH treatment, other efforts to control these diseases remain unsatisfactory. Given the projected rise in incidence, it urgent novel effective strategies prevalent In this article, pathogenic mechanisms of MASH, insulin resistance, dysregulated nuclear signaling, genetic risk factors (eg, patatin-like phospholipase domain-containing 3 hydroxysteroid 17-β dehydrogenase-13), introduced. Various interventions then explored, medication (resmetirom), drugs that currently clinical trials glucagon-like peptide 1 agonist, fibroblast growth factor 21 analog, PPAR agonist), those failed previous obeticholic acid stearoyl-CoA desaturase antagonist). Moreover, given role gut microbes increasingly acknowledged, alterations microbiota microbial development elucidated. Therapeutic approaches target dietary intervention probiotics) further explored. With better understanding multifaceted mechanisms, innovative therapeutics root causes greatly facilitated. The possibility alleviating achieving patient outcomes within reach. SIGNIFICANCE STATEMENT: (MASLD) most common worldwide, progress steatohepatitis, cancer. Better has facilitated strategies. increasing evidence illustrated crucial pathogenesis It may be clinically feasible alleviate future.

Язык: Английский

---

Gut–Liver–Pancreas Axis Crosstalk in Health and Disease: From the Role of Microbial Metabolites to Innovative Microbiota Manipulating Strategies

Biomedicines, Год журнала: 2024, Номер 12(7), С. 1398 - 1398

Опубликована: Июнь 24, 2024

The functions of the gut are closely related to those many other organs in human body. Indeed, microbiota (GM) metabolize several nutrients and compounds that, once released bloodstream, can reach distant organs, thus influencing metabolic inflammatory tone host. main microbiota-derived metabolites responsible for modulation endocrine responses short-chain fatty acids (SCFAs), bile glucagon-like peptide 1 (GLP-1). These molecules (i) regulate pancreatic hormones (insulin glucagon), (ii) increase glycogen synthesis liver, (iii) boost energy expenditure, especially skeletal muscles brown adipose tissue. In words, they critical maintaining glucose lipid homeostasis. GM dysbiosis, imbalance microbiota-related products affect proper functions, including gut–liver–pancreas axis (GLPA). addition, dysbiosis contribute onset some diseases such as non-alcoholic steatohepatitis (NASH)/non-alcoholic liver disease (NAFLD), hepatocellular carcinoma (HCC), type 2 diabetes (T2D). this review, we explored roles their involvement progression these diseases. detailed microbiota-modulating strategies that could improve diseases’ development by restoring healthy balance GLPA.

Язык: Английский

---

Gut microbiota-derived short chain fatty acids act as mediators of the gut-liver-brain axis

Metabolic Brain Disease, Год журнала: 2025, Номер 40(2)

Опубликована: Фев. 8, 2025

Язык: Английский

---

Emerging insights into the gut microbiota as a key regulator of immunity and response to immunotherapy in hepatocellular carcinoma

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Фев. 25, 2025

The gut microbiota, a complex microbial ecosystem closely connected to the liver via portal vein, has emerged as critical regulator of health and disease. Numerous studies have underscored its role in onset progression disorders, including alcoholic disease, metabolic dysfunction-associated steatotic disease (MASLD), steatohepatitis (MASH), fibrosis, cirrhosis, hepatocellular carcinoma (HCC). This review provides comprehensive overview current insights into influence microbiota on HCC progression, particularly effects immune cells within tumor microenvironment (TME). Furthermore, we explore potential microbiota-targeted interventions, such antibiotics, probiotics, prebiotics, fecal transplantation (FMT), modulate response improve outcomes immunotherapy HCC. By synthesizing from recent studies, this aims highlight microbiota-based strategies that may enhance outcomes, advancing personalized approaches treatment.

Язык: Английский

---

Modulation of gut microbiota by probiotics to improve the efficacy of immunotherapy in hepatocellular carcinoma

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Ноя. 22, 2024

Hepatocellular carcinoma, a common malignancy of the digestive system, typically progresses through sequence hepatitis, liver fibrosis, cirrhosis and ultimately, tumor. The interaction between gut microbiota, portal venous system biliary tract, referred to as gut-liver axis, is crucial in understanding mechanisms that contribute progression hepatocellular carcinoma. Mechanisms implicated include dysbiosis, alterations microbial metabolites increased intestinal barrier permeability. Imbalances or contributes carcinoma by producing carcinogenic substances, disrupting balance immune altering metabolic processes, increasing Concurrently, accumulating evidence suggests microbiota has ability modulate antitumor responses affect efficacy cancer immunotherapies. As new effective strategy, immunotherapy offers significant potential for managing advanced stages with checkpoint inhibitors achieving advancements improving patients' survival. Probiotics play vital role promoting health preventing diseases modulating inflammation responses. Research indicates they are instrumental boosting modulation microbiota. This review explore relationship emergence assess contributions probiotics outline latest research findings, providing safer more cost-effective strategy prevention management

Язык: Английский

---