Bile Acids and Biliary Fibrosis DOI Creative Commons
Sayed Obaidullah Aseem, Phillip B. Hylemon, Huiping Zhou

et al.

Cells, Journal Year: 2023, Volume and Issue: 12(5), P. 792 - 792

Published: March 2, 2023

Biliary fibrosis is the driving pathological process in cholangiopathies such as primary biliary cholangitis (PBC) and sclerosing (PSC). Cholangiopathies are also associated with cholestasis, which retention of components, including bile acids, liver blood. Cholestasis may worsen fibrosis. Furthermore, acid levels, composition homeostasis dysregulated PBC PSC. In fact, mounting data from animal models human suggest that acids play a crucial role pathogenesis progression The identification receptors has advanced our understanding various signaling pathways involved regulating cholangiocyte functions potential impact on We will briefly review recent findings linking these epigenetic regulatory mechanisms. Further detailed uncover additional therapeutic avenues for cholangiopathies.

Language: Английский

Bile acids as modulators of gut microbiota composition and function DOI Creative Commons

Anaïs Larabi,

Hugo L. P. Masson, Andreas J. Bäumler

et al.

Gut Microbes, Journal Year: 2023, Volume and Issue: 15(1)

Published: Feb. 5, 2023

Changes in the composition of gut-associated microbial communities are associated with many human illnesses, but factors driving dysbiosis remain incompletely understood. One factor governing microbiota gut is bile. Bile acids shape through their antimicrobial activity and by activating host signaling pathways that maintain homeostasis. Although bile host-derived, functions integrally linked to bacterial metabolism, which shapes intestinal acid pool. Conditions change size or pool can trigger alterations exacerbate inflammation favor infection opportunistic pathogens. Therefore, manipulating might be a promising strategy remediate dysbiosis.

Language: Английский

Citations

143
Gut dysbiosis in nonalcoholic fatty liver disease: pathogenesis, diagnosis, and therapeutic implications DOI Creative Commons
Jie Fang, Chen-Huan Yu, Xuejian Li

et al.

Frontiers in Cellular and Infection Microbiology, Journal Year: 2022, Volume and Issue: 12

Published: Nov. 8, 2022

The incidence of nonalcoholic fatty liver disease (NAFLD) is increasing recently and has become one the most common clinical diseases. Since pathogenesis NAFLD not been completely elucidated, few effective therapeutic drugs are available. As “second genome” human body, gut microbiota plays an important role in digestion, absorption metabolism food drugs. Gut can act as driver to advance occurrence development NAFLD, accelerate its progression cirrhosis hepatocellular carcinoma. Growing evidence demonstrated that metabolites directly affect intestinal morphology immune response, resulting abnormal activation inflammation endotoxemia; dysbiosis also causes dysfunction gut-liver axis via alteration bile acid pathway. Because composition diversity disease-specific expression characteristics, holds strong promise novel biomarkers targets for NAFLD. Intervening microbiota, such antibiotic/probiotic treatment fecal transplantation, a strategy preventing treating In this article, we have reviewed emerging functions association bacterial components different stages discussed potential implications diagnosis therapy.

Language: Английский

Citations

102
Bile acid metabolism and signaling in health and disease: molecular mechanisms and therapeutic targets DOI Creative Commons
Joshua S. Fleishman, Sunil Kumar

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: April 25, 2024

Bile acids, once considered mere dietary surfactants, now emerge as critical modulators of macronutrient (lipid, carbohydrate, protein) metabolism and the systemic pro-inflammatory/anti-inflammatory balance. acid signaling pathways play a crucial role in protecting against, or if aberrant, inducing cardiometabolic, inflammatory, neoplastic conditions, strongly influencing health disease. No curative treatment exists for any bile influenced disease, while most promising well-developed therapeutic was recently rejected by FDA. Here, we provide bottom-up approach on mechanistically explaining their biochemistry, physiology, pharmacology at canonical non-canonical receptors. Using this mechanistic model explain how abnormal physiology drives disease pathogenesis, emphasizing ceramide synthesis may serve unifying pathogenic feature cardiometabolic diseases. We an in-depth summary pre-existing receptor modulators, shortcomings, propose solutions they be remedied. Lastly, rationalize novel targets further translational drug discovery future perspectives. Rather than dismissing therapeutics due to recent setbacks, believe that there is immense clinical potential high likelihood success therapeutics.

Language: Английский

Citations

72
FXR agonists in NASH treatment DOI Creative Commons
Luciano Adorini, Michael Trauner

Journal of Hepatology, Journal Year: 2023, Volume and Issue: 79(5), P. 1317 - 1331

Published: Aug. 9, 2023

The farnesoid X receptor (FXR), a bile acid (BA)-activated nuclear highly expressed in the liver and intestine, regulates expression of genes involved cholesterol homeostasis, hepatic gluconeogenesis, lipogenesis, inflammation fibrosis, addition to controlling intestinal barrier integrity, preventing bacterial translocation maintaining gut microbiota eubiosis. Non-alcoholic steatohepatitis (NASH), an advanced stage non-alcoholic fatty disease, is characterized by steatosis, hepatocyte damage (ballooning) inflammation, leading cirrhosis hepatocellular carcinoma. NASH represents major unmet medical need, but no pharmacological treatments have yet been approved. pleiotropic mechanisms development offer range therapeutic opportunities among them FXR activation has emerged as established target. Various agonists with different physicochemical properties, which can be broadly classified BA derivatives, non-BA-derived steroidal agonists, non-steroidal partial are clinical development. In this review we will summarize key preclinical features most critically evaluate their potential treatment.

Language: Английский

Citations

54
Gut-liver axis: Pathophysiological concepts and medical perspective in chronic liver diseases DOI Creative Commons
Susana Rodrigues, Van der Merwe, Aleksander Krag

et al.

Seminars in Immunology, Journal Year: 2024, Volume and Issue: 71, P. 101859 - 101859

Published: Jan. 21, 2024

Language: Английский

Citations

19
The Gut–Vascular Barrier as a New Protagonist in Intestinal and Extraintestinal Diseases DOI Open Access

Natalia Di Tommaso,

Francesco Santopaolo, Antonio Gasbarrini

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(2), P. 1470 - 1470

Published: Jan. 12, 2023

The intestinal barrier, with its multiple layers, is the first line of defense between outside world and intestine. Its disruption, resulting in increased permeability, a recognized pathogenic factor extra-intestinal diseases. identification gut-vascular barrier (GVB), consisting structured endothelium below epithelial layer, has led to new evidence on etiology management diseases gut-liver axis gut-brain axis, recent implications oncology as well. involved several neuroinflammatory processes. In particular, description choroid plexus vascular regulating brain permeability under conditions gut inflammation identifies key regulator maintaining tissue homeostasis health.

Language: Английский

Citations

30
Collaborative Metabolism: Gut Microbes Play a Key Role in Canine and Feline Bile Acid Metabolism DOI Creative Commons
John C. Rowe, Jenessa A. Winston

Veterinary Sciences, Journal Year: 2024, Volume and Issue: 11(2), P. 94 - 94

Published: Feb. 18, 2024

Bile acids, produced by the liver and secreted into gastrointestinal tract, are dynamic molecules capable of impacting overall health dogs cats in many contexts. Importantly, gut microbiota metabolizes host primary bile acids chemically distinct secondary acids. This review explores emergence new literature connecting microbial-derived acid metabolism to canine feline disease. Moreover, this highlights multi-omic methodologies for translational research as an area continued growth veterinary medicine aimed at accelerating microbiome science it pertains cats.

Language: Английский

Citations

11
Fine-tuning the gut ecosystem: the current landscape and outlook of artificial microbiome therapeutics DOI
Serena Porcari, William G. Fusco, Igor Spivak

et al.

˜The œLancet. Gastroenterology & hepatology, Journal Year: 2024, Volume and Issue: 9(5), P. 460 - 475

Published: April 8, 2024

Language: Английский

Citations

9
Recent Advances in the Digestive, Metabolic and Therapeutic Effects of Farnesoid X Receptor and Fibroblast Growth Factor 19: From Cholesterol to Bile Acid Signaling DOI Open Access
Agostino Di Ciaula, Leonilde Bonfrate, Jacek Baj

et al.

Nutrients, Journal Year: 2022, Volume and Issue: 14(23), P. 4950 - 4950

Published: Nov. 22, 2022

Bile acids (BA) are amphiphilic molecules synthesized in the liver (primary BA) starting from cholesterol. In small intestine, BA act as strong detergents for emulsification, solubilization and absorption of dietary fat, cholesterol, lipid-soluble vitamins. Primary escaping active ileal re-absorption undergo microbiota-dependent biotransformation to secondary colon, passive diffusion into portal vein towards liver. also signaling able play a systemic role variety metabolic functions, mainly through activation nuclear membrane-associated receptors gallbladder, homeostasis is tightly controlled by complex interplay with receptor farnesoid X (FXR), enterokine hormone fibroblast growth factor 15 (FGF15) or human ortholog FGF19 (FGF19). Circulating FGFR4/β-Klotho causes smooth muscle relaxation refilling gallbladder. binding activates FXR-small heterodimer partner (SHP) pathway. This step suppresses unnecessary synthesis promotes continuous enterohepatic circulation BAs. Besides homeostasis, BA-FXR-FGF19 axis governs several processes, hepatic protein, glycogen synthesis, without inducing lipogenesis. These pathways can be disrupted cholestasis, nonalcoholic fatty disease, hepatocellular carcinoma. Thus, targeting FXR activity represent novel therapeutic approach prevention treatment diseases.

Language: Английский

Citations

31
360-Degree Perspectives on Obesity DOI Creative Commons
Magdalena Cuciureanu,

Cătălin-Cezar Caratașu,

Levon Gabrielian

et al.

Medicina, Journal Year: 2023, Volume and Issue: 59(6), P. 1119 - 1119

Published: June 9, 2023

Alarming statistics show that the number of people affected by excessive weight has surpassed 2 billion, representing approximately 30% world's population. The aim this review is to provide a comprehensive overview one most serious public health problems, considering obesity requires an integrative approach takes into account its complex etiology, including genetic, environmental, and lifestyle factors. Only understanding connections between many contributors synergy treatment interventions can ensure satisfactory outcomes in reducing obesity. Mechanisms such as oxidative stress, chronic inflammation, dysbiosis play crucial role pathogenesis associated complications. Compounding factors deleterious effects novel challenge posed obesogenic digital (food) environment, stigma with should not be overlooked. Preclinical research animal models been instrumental elucidating these mechanisms, translation clinical practice provided promising therapeutic options, epigenetic approaches, pharmacotherapy, bariatric surgery. However, more studies are necessary discover new compounds target key metabolic pathways, innovative ways deliver drugs, optimal combinations allopathic treatments, and, last but least, emerging biological markers for effective monitoring. With each passing day, crisis tightens grip, threatening only individual lives also burdening healthcare systems societies at large. It high time we took action confront urgent imperative address escalating global head-on.

Language: Английский

Citations

20