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Gut-liver axis

Murphy L Y Wan, Hani El-Nezami
Hepatocellular carcinoma (HCC), the most common primary liver cancer, is one of the dreaded complications of chronic liver disease. Recent experimental and clinical studies have revealed that the alteration of gut-liver axis plays a pivotal role in the onset of chronic liver diseases, including HCC. Altered gut microbiota and endotoxemia are increasingly recognized as critical components in promoting the progression of chronic liver diseases to HCC. Probiotics have been suggested as a novel, safe and cost-effective approach to prevent or treat HCC...
February 2018: Hepatobiliary Surgery and Nutrition
Kai Markus Schneider, Stefanie Albers, Christian Trautwein
No abstract text is available yet for this article.
March 5, 2018: Journal of Hepatology
Henrik Maagensen, Anders E Junker, Niklas R Jørgensen, Lise L Gluud, Filip K Knop, Tina Vilsbøll
Context: Non-alcoholic fatty liver disease (NAFLD) is associated with type 2 diabetes (T2D) and vice versa, and both conditions are associated with an increased risk of fractures and altered bone turnover. While NAFLD patients typically suffer from decreased bone mineral density (BMD), T2D is associated with normal to high BMD. The pathophysiology is uncertain, but may involve the gut-bone axis. Objective: We investigated the influence of the gut on glucose-induced changes in plasma bone turnover markers in healthy controls and patients with T2D and/or biopsy-verified NAFLD...
March 1, 2018: Journal of Clinical Endocrinology and Metabolism
Andrea Mancini, Francesca Campagna, Piero Amodio, Kieran M Tuohy
Hepatic encephalopathy (HE) is a debilitating neuropsychiatric condition often associated with acute liver failure or cirrhosis. Advanced liver diseases are characterized by a leaky gut and systemic inflammation. There is strong evidence that the pathogenesis of HE is linked to a dysbiotic gut microbiota and to harmful microbial by-products, such as ammonia, indoles, oxindoles and endotoxins. Increased concentrations of these toxic metabolites together with the inability of the diseased liver to clear such products is thought to play an important patho-ethiological role...
February 27, 2018: Food & Function
Fabian J Bolte, Barbara Rehermann
The broadening field of microbiome research has led to a substantial reappraisal of the gut-liver axis and its role in chronic liver disease. The liver is a central immunologic organ that is continuously exposed to food and microbial-derived antigens from the gastrointestinal tract. Mucosal-associated invariant T (MAIT) cells are enriched in the human liver and can be activated by inflammatory cytokines and microbial antigens. In chronic inflammatory liver disease, MAIT cells are depleted suggesting an impaired MAIT cell-dependent protection against bacterial infections...
February 2018: Seminars in Liver Disease
Anne Abot, Alexandre Lucas, Tereza Bautzova, Arnaud Bessac, Audren Fournel, Sophie Le-Gonidec, Philippe Valet, Cédric Moro, Patrice D Cani, Claude Knauf
OBJECTIVE: Decreasing duodenal contraction is now considered as a major focus for the treatment of type 2 diabetes. Therefore, identifying bioactive molecules able to target the enteric nervous system, which controls the motility of intestinal smooth muscle cells, represents a new therapeutic avenue. For this reason, we chose to study the impact of oral galanin on this system in diabetic mice. METHODS: Enteric neurotransmission, duodenal contraction, glucose absorption, modification of gut-brain axis, and glucose metabolism (glucose tolerance, insulinemia, glucose entry in tissue, hepatic glucose metabolism) were assessed...
January 31, 2018: Molecular Metabolism
Abdul-Rizaq Hamoud, Lauren Weaver, David E Stec, Terry D Hinds
Bilirubin is a component of the heme catabolic pathway that is essential for liver function and has been shown to reduce hepatic fat accumulation. High plasma bilirubin levels are reflective of liver disease due to an injurious effect on hepatocytes. In healthy liver, bilirubin is conjugated and excreted to the intestine and converted by microbes to urobilinoids, which are reduced to the predominant pigment in feces, stercobilin, or reabsorbed. The function of urobilinoids in the gut or their physiological relevance of reabsorption is not well understood...
February 3, 2018: Trends in Endocrinology and Metabolism: TEM
Mei Zhou, R Marc Learned, Stephen J Rossi, Alex M DePaoli, Hui Tian, Lei Ling
Nonalcoholic fatty liver disease (NAFLD) is an increasingly prevalent chronic liver disease for which no approved therapies are available. Despite intensive research, the cellular mechanisms that mediate NAFLD pathogenesis and progression are poorly understood. Although obesity, diabetes, insulin resistance, and related metabolic syndrome, all consequences of a Western diet lifestyle, are well-recognized risk factors for NAFLD development, dysregulated bile acid metabolism is emerging as a novel mechanism contributing to NAFLD pathogenesis...
December 2017: Hepatology Communications
Seiichi Ishida
Assay systems using in vitro cultured cells are increasingly applied for evaluation of the efficacy, safety, and toxicity of drug candidates. In vitro cell-based assays have two main applications in the drug discovery process: searching for a compound that is effective against the target disease (seed investigation) and confirmation of safety during use of the identified compounds (safety assessment). Currently available in vitro cell-based assays have been designed to evaluate the efficacy and toxicity in single organs, but the in vivo pharmacokinetics and pharmacodynamics of the administered drug candidates have not been considered...
January 11, 2018: Drug Metabolism and Pharmacokinetics
Bo Li, Kenan Guo, Li Zeng, Benhua Zeng, Ran Huo, Yuanyuan Luo, Haiyang Wang, Meixue Dong, Peng Zheng, Chanjuan Zhou, Jianjun Chen, Yiyun Liu, Zhao Liu, Liang Fang, Hong Wei, Peng Xie
Major depressive disorder (MDD) is a common mood disorder. Gut microbiota may be involved in the pathogenesis of depression via the microbe-gut-brain axis. Liver is vulnerable to exposure of bacterial products translocated from the gut via the portal vein and may be involved in the axis. In this study, germ-free mice underwent fecal microbiota transplantation from MDD patients and healthy controls. Behavioral tests verified the depression model. Metabolomics using gas chromatography-mass spectrometry, nuclear magnetic resonance, and liquid chromatography-mass spectrometry determined the influence of microbes on liver metabolism...
January 31, 2018: Translational Psychiatry
Gyorgy Baffy
Nonalcoholic fatty liver disease (NAFLD) advanced to cirrhosis is often complicated by clinically significant portal hypertension, which is primarily caused by increased intrahepatic vascular resistance. Liver fibrosis has been identified as a critical determinant of this process. However, there is evidence that portal venous pressure may begin to rise in the earliest stages of NAFLD when fibrosis is far less advanced or absent. The biological and clinical significance of these early changes in sinusoidal homeostasis remains unclear...
March 2018: Digestive Diseases and Sciences
Peter Stärkel, Sophie Leclercq, Philippe de Timary, Bernd Schnabl
Alcohol dependence and alcoholic liver disease represent a major public health problem with substantial morbidity and mortality. By yet incompletely understood mechanisms, chronic alcohol abuse is associated with increased intestinal permeability and alterations of the gut microbiota composition, allowing bacterial components, bacteria, and metabolites to reach the portal and the systemic circulation. These gut-derived bacterial products are recognized by immune cells circulating in the blood or residing in remote organs such as the liver leading to the release of pro-inflammatory cytokines which are considered important mediators of the liver-gut-brain communication...
January 31, 2018: Clinical Science (1979-)
Youngshim Choi, Mohamed A Abdelmegeed, Byoung-Joon Song
Indole-3-carbinol (I3C), found in Brassica family vegetables, exhibits antioxidant, anti-inflammatory, and anti-cancerous properties. Here, we aimed to evaluate the preventive effects of I3C against ethanol (EtOH)-induced liver injury and study the protective mechanism(s) by using the well-established chronic-plus-binge alcohol exposure model. The preventive effects of I3C were evaluated by conducting various histological, biochemical, and real-time PCR analyses in mouse liver, adipose tissue, and colon, since functional alterations of adipose tissue and intestine can also participate in promoting EtOH-induced liver damage...
December 10, 2017: Journal of Nutritional Biochemistry
Lorenzo A Orci, Stéphanie Lacotte, Vaihere Delaune, Florence Slits, Graziano Oldani, Vladimir Lazarevic, Carlo Rossetti, Laura Rubbia-Brandt, Philippe Morel, Christian Toso
BACKGROUND & AIMS: There is growing evidence that liver graft ischemia-reperfusion (I/R) is a risk factor for hepatocellular carcinoma (HCC) recurrence, but the involved mechanisms are unclear. Here, we tested the hypothesis that mesenteric congestion due to portal blood flow interruption induces endotoxin-mediated Toll-Like Receptor 4 (Tlr4) engagement, resulting in elevated liver cancer burden. We also assessed the role of remote ischemic preconditioning (RIPC) in this context. METHODS: C57Bl/6j mice were exposed to standardized models of liver I/R injury and RIPC, by occluding hepatic and femoral blood vessels...
January 10, 2018: Journal of Hepatology
John Y L Chiang, Jessica M Ferrell
Bile acids facilitate intestinal nutrient absorption and biliary cholesterol secretion to maintain bile acid homeostasis, which is essential for protecting liver and other tissues and cells from cholesterol and bile acid toxicity. Bile acid metabolism is tightly regulated by bile acid synthesis in the liver and bile acid biotransformation in the intestine. Bile acids are endogenous ligands that activate a complex network of nuclear receptor farnesoid X receptor and membrane G protein-coupled bile acid receptor-1 to regulate hepatic lipid and glucose metabolic homeostasis and energy metabolism...
January 11, 2018: Gene Expression
Laura McEnerney, Kara Duncan, Bo-Ram Bang, Sandra Elmasry, Meng Li, Toshio Miki, Sadeesh K Ramakrishnan, Yatrik M Shah, Takeshi Saito
The hepatic lobule is divided into three zones along the portal-central vein axis. Hepatocytes within each zone exhibit a distinctive gene expression profile that coordinates their metabolic compartmentalization. The zone-dependent heterogeneity of hepatocytes has been hypothesized to result from the differential degree of exposure to oxygen, nutrition and gut-derived toxins. In addition, the gradient of Wnt signaling that increases towards the central vein seen in rodent models is believed to play a critical role in shaping zonation...
December 15, 2017: Experimental & Molecular Medicine
Xiaojiao Zheng, Fengjie Huang, Aihua Zhao, Sha Lei, Yunjing Zhang, Guoxiang Xie, Tianlu Chen, Chun Qu, Cynthia Rajani, Bing Dong, Defa Li, Wei Jia
BACKGROUND: Intestinal bacteria are known to regulate bile acid (BA) homeostasis via intestinal biotransformation of BAs and stimulation of the expression of fibroblast growth factor 19 through intestinal nuclear farnesoid X receptor (FXR). On the other hand, BAs directly regulate the gut microbiota with their strong antimicrobial activities. It remains unclear, however, how mammalian BAs cross-talk with gut microbiome and shape microbial composition in a dynamic and interactive way. RESULTS: We quantitatively profiled small molecule metabolites derived from host-microbial co-metabolism in mice, demonstrating that BAs were the most significant factor correlated with microbial alterations among all types of endogenous metabolites...
December 14, 2017: BMC Biology
Irene Pierantonelli, Chiara Rychlicki, Laura Agostinelli, Debora Maria Giordano, Melania Gaggini, Cristina Fraumene, Chiara Saponaro, Valeria Manghina, Loris Sartini, Eleonora Mingarelli, Claudio Pinto, Emma Buzzigoli, Luciano Trozzi, Antonio Giordano, Marco Marzioni, Samuele De Minicis, Sergio Uzzau, Saverio Cinti, Amalia Gastaldelli, Gianluca Svegliati-Baroni
A correction to this article has been published and is linked from the HTML version of this paper. The error has been fixed in the paper.
December 11, 2017: Scientific Reports
Qingqing Wang, Bin Wang, Vijay Saxena, Lili Miles, Josh Tiao, Joel E Mortensen, Jaimie D Nathan
BACKGROUND: The mechanisms by which intestinal bacteria impact liver diseases remain poorly understood. The aim of this study was to develop a mouse model of small-bowel bacterial overgrowth and to determine its impact on hepatobiliary injury. MATERIALS AND METHODS: A jejunal self-filling blind loop (SFBL) was created in C57BL/6 mice. Three weeks after surgery, the mice were euthanized, and bacterial cultures of luminal content of the loop and extraintestinal tissues were performed...
January 2018: Journal of Surgical Research
Tao Zhang, Kewei Sun, Ya Wang, Lei Huang, Ren Lang, Wei Jiang
Acute-on-chronic liver failure (ACLF) is characterized by organ failure mediated by acute decompensation of cirrhosis. Recent studies have highlighted the importance of the gut-liver axis (GLS) and its association with ACLF pathogenesis. In this review, we discuss the mechanisms related to the alteration of the GLA and their involvement in ACLF pathogenesis and suggest some possible therapeutic options that could modulate the GLA dysfunction. This knowledge may provide information useful for the design of therapeutic strategies for gut dysbiosis and its complications in ACLF...
February 2018: European Journal of Gastroenterology & Hepatology
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