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Gut-liver axis

Abdel-Naser Elzouki
Probiotics are live, nonpathogenic bacteria capable of colonizing the colonic mucosa. The most common probiotics include strains of Lactobacillus or Bifidobacteria, which are part of the normal gastrointestinal microbiota. Initial studies of selected probiotic species have suggested potential efficacy in several gastrointestinal diseases including inflammatory bowel diseases (particularly pouchitis), antibiotic-related diarrhea, Clostridium difficile toxin-induced colitis, infectious diarrhea, irritable bowel syndrome, and allergy...
November 2016: Journal of Clinical Gastroenterology
Ilaria Spadoni, Alessandro Pietrelli, Graziano Pesole, Maria Rescigno
It has been widely demonstrated that tolerance against gut microbiota is compartmentalized to mucosal sites where microbes mostly reside. How the commensal bacteria are excluded from the entrance into the blood stream via intestinal capillaries that are located beneath the gut epithelium was not clear. We recently described the existence of a new anatomical structure, the 'gut vascular barrier' (GVB), both in murine and human intestines that plays a fundamental role in avoiding indiscriminate trafficking of bacteria from the gut into the blood circulation...
October 10, 2016: Gut Microbes
Serge J Zweers, Elisabeth M de Vries, Martin Lenicek, Dagmar Tolenaars, D Rudi de Waart, Kiran V K Koelfat, Albert K Groen, Steven W M Olde Damink, Ulrich Beuers, Cyriel Ponsioen, Peter L M Jansen, Frank G Schaap
BACKGROUND: Bile salts likely contribute to liver injury in patients with primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC). Fibroblast growth factor 19 (FGF19) is a bile salt-induced enterokine with hepatoprotective potential as it suppresses de novo bile salt synthesis. Here, we evaluated the bile salt receptor FXR/FGF19 gut-liver axis in PSC and PBC patients. METHODS: Fasted patients with PSC (n = 12) and PBC (n = 10), and healthy controls (HC; n = 10) were orally challenged with the natural FXR agonist chenodeoxycholic acid (CDCA 15 mg/kg)...
September 30, 2016: Hepatology International
Maria Grazia Clemente, Claudia Mandato, Marco Poeta, Pietro Vajro
Non-alcoholic fatty liver disease (NAFLD) in children is becoming a major health concern. A "multiple-hit" pathogenetic model has been suggested to explain the progressive liver damage that occurs among children with NAFLD. In addition to the accumulation of fat in the liver, insulin resistance (IR) and oxidative stress due to genetic/epigenetic background, unfavorable lifestyles, gut microbiota and gut-liver axis dysfunction, and perturbations of trace element homeostasis have been shown to be critical for disease progression and the development of more severe inflammatory and fibrotic stages [non-alcoholic steatohepatitis (NASH)]...
September 28, 2016: World Journal of Gastroenterology: WJG
Silvana Gaetani, Adele Romano, Gustavo Provensi, Valdo Ricca, Thomas Lutz, Maria Beatrice Passani
The central nervous system and viscera constitute a functional ensemble, the gut-brain axis, that allows bidirectional information flow that contributes to the control of feeding behavior based not only on the homeostatic, but also on the hedonic aspects of food intake. The prevalence of eating disorders, such as anorexia nervosa, binge eating and obesity, poses an enormous clinical burden, and involves an ever-growing percentage of the population worldwide. Clinical and preclinical research is constantly adding new information to the field and orienting further studies with the aim of providing a foundation for developing more specific and effective treatment approaches to pathological conditions...
September 21, 2016: Journal of Neurochemistry
Yaron Rotman, Arun J Sanyal
Given the high prevalence and rising incidence of non-alcoholic fatty liver disease (NAFLD), the absence of approved therapies is striking. Although the mainstay of treatment of NAFLD is weight loss, it is hard to maintain, prompting the need for pharmacotherapy as well. A greater understanding of disease pathogenesis in recent years was followed by development of new classes of medications, as well as potential repurposing of currently available agents. NAFLD therapies target four main pathways. The dominant approach is targeting hepatic fat accumulation and the resultant metabolic stress...
September 19, 2016: Gut
Frank J Gonzalez, Changtao Jiang, Andrew D Patterson
The gut microbiota is associated with metabolic diseases including obesity, insulin resistance, and nonalcoholic fatty liver disease, as shown by correlative studies and by transplant of microbiota from obese humans and mice into germ-free mice. Modification of the microbiota by treatment of high-fat diet (HFD)-fed mice with tempol or antibiotics resulted in decreased adverse metabolic phenotypes. This was owing to lower levels of the genera Lactobacillus and decreased bile salt hydrolase (BSH) activity. The decreased BSH resulted in increased levels of tauro-β-muricholic acid (MCA), a substrate of BSH and a potent farnesoid X receptor (FXR) antagonist...
September 14, 2016: Gastroenterology
Monika Rau, Bruno Stieger, Maria J Monte, Johannes Schmitt, Daniel Jahn, Isabelle Frey-Wagner, Tina Raselli, Jose J G Marin, Beat Müllhaupt, Gerhard Rogler, Andreas Geier
BACKGROUND: Fibroblast growth factor (FGF) 15/19 is part of the gut-liver crosstalk accounting for bile acid (BA) metabolism regulation. Dysregulation of fibroblast growth factor 15/19 signaling is observed in different pathological conditions, for example, in gastrointestinal diseases such as inflammatory bowel disease (IBD). To understand the molecular bases, we analyzed the enterohepatic regulation of Fgf15-mediated pathway in 2 different inflammatory bowel disease mouse models. METHODS: Target genes of the BA-farnesoid-X-receptor (Fxr)-Ffg15 axis were quantified by RT-PCR or western blotting in gut and liver of dextran sulfate sodium (DSS)-treated and IL10 mice...
October 2016: Inflammatory Bowel Diseases
Xudong Hu, Alvin Jogasuria, Jiayou Wang, Chunki Kim, Yoonhee Han, Hong Shen, Jiashin Wu, Min You
MitoNEET (mNT) (CDGSH iron-sulfur domain-containing protein 1 or CISD1) is an outer mitochondrial membrane protein that donates 2Fe-2S clusters to apo-acceptor proteins. In the present study, using a global mNT knock out (mNTKO) mouse model, we investigated in vivo functional role of mNT in the development of alcoholic steatohepatitis. Experimental alcoholic steatohepatitis was achieved by pair feeding wild-type (WT) and mNTKO mice with Lieber-DeCarli ethanol-containing diets for 4-wks. Strikingly, chronically ethanol-fed mNTKO mice were completely resistant to ethanol-induced steatohepatitis as revealed by dramatically reduced hepatic triglycerides, decreased hepatic cholesterol level, diminished liver inflammatory response and normalized serum ALT levels...
August 29, 2016: Journal of Biological Chemistry
Giovanni Musso, Franco De Michieli, Daria Bongiovanni, Renato Parente, Luciana Framarin, Nicola Leone, Mara Berrutti, Roberto Gambino, Maurizio Cassader, Solomon Cohney, Elena Paschetta
Epidemiological data set an association between the prevalence and severity of NAFLD and the incidence and stage of chronic kidney disease(CKD); furthermore, NASH-related cirrhosis has a higher risk of renal failure, a greater necessity for simultaneous liver-kidney transplantation(SLKT) and a poorer renal outcome than cirrhosis of other etiologies even after SLKT. These data suggest NASH and CKD share common proinflammatory and profibrotic mechanisms of progression, which are incompletely targeted by current treatments...
August 10, 2016: Clinical Gastroenterology and Hepatology
Emidio Scarpellini, Mariana Forlino, Marinella Lupo, Carlo Rasetti, Giammarco Fava, Ludovico Abenavoli, Adriano De Santis
The gut-liver axis model has often explained liver disease physiopathology. Among the latter we can mention Non-Alcoholic Liver Steatosis (NAFLD), Liver Steatohepatitis (NASH), liver cirrhosis. In this frame an altered Intestinal Permeability (IP) is the gate for antigenic/toxic substances from gut lumen until target organs such as liver in NAFLD. Altered intestinal permeability was discovered almost forty years ago as consequence of acute and chronic alcohol ingestion. Alcohol Liver Disease (ALD) is a systemic pathology whose beginning and end belong to the intestine...
2016: Reviews on Recent Clinical Trials
Srinivasan Dasarathy, Manuela Merli
Sarcopenia or loss of skeletal muscle mass is the major component of malnutrition and is a frequent complication in cirrhosis that adversely affects clinical outcomes. These include survival, quality of life, development of other complications and post liver transplantation survival. Radiological image analysis is currently utilized to diagnose sarcopenia in cirrhosis. Nutrient supplementation and physical activity are used to counter sarcopenia but have not been consistently effective because the underlying molecular and metabolic abnormalities persist or are not influenced by these treatments...
August 8, 2016: Journal of Hepatology
Tianru Jin, Jianping Weng
GLP-1 and its based drugs possess extrapancreatic metabolic functions, including that in the liver. These direct hepatic metabolic functions explain their therapeutic efficiency for subjects with insulin resistance. The direct hepatic functions could be mediated by previously assumed "degradation" products of GLP-1 without involving canonic GLP-1R. Although GLP-1 analogs were created as therapeutic incretins, extrapancreatic functions of these drugs, as well as native GLP-1, have been broadly recognized. Among them, the hepatic functions are particularly important...
September 1, 2016: American Journal of Physiology. Endocrinology and Metabolism
Xingyong Wan, Chengfu Xu, Chaohui Yu, Youming Li
Nonalcoholic fatty liver disease (NAFLD) has been recognized as a major public health problem worldwide. Nonalcoholic steatohepatitis (NASH) is an advanced form of NAFLD that may progress to cirrhosis and hepatocellular carcinoma. The pathogenesis of disease progression from NAFLD to NASH has not been fully understood. Immunological mechanisms that have been increasingly recognized in the disease progression include defects in innate immunity, adaptive immunity, Toll-like receptor (TLR) signaling, and gut-liver axis...
2016: Canadian Journal of Gastroenterology & Hepatology
Silvia M Ferolla, Cláudia A Couto, Luciana Costa-Silva, Geyza N A Armiliato, Cristiano A S Pereira, Flaviano S Martins, Maria de Lourdes A Ferrari, Eduardo G Vilela, Henrique O G Torres, Aloísio S Cunha, Teresa C A Ferrari
Nonalcoholic fatty liver disease is the most prevalent chronic liver disease in Western countries; it can progress to nonalcoholic steatohepatitis (NASH), cirrhosis and hepatocarcinoma. The importance of gut-liver-adipose tissue axis has become evident and treatments targeting gut microbiota may improve inflammatory and metabolic parameters in NASH patients. In a randomized, controlled clinical trial, involving 50 biopsy-proven NASH patients, we investigated the effects of synbiotic supplementation on metabolic parameters, hepatic steatosis, intestinal permeability, small intestinal bacterial overgrowth (SIBO) and lipopolysaccharide (LPS) serum levels...
2016: Nutrients
Byoungjin Park, Hye-Ree Lee, Yong-Jae Lee
Alcohol-related liver disease is implicated in gut disturbances, both functionally and structurally. The gut-liver interaction has been noticed as an important feature of the prevention of systemic inflammation as well as liver health. Optimal functioning of the gut-liver axis depends on gut health. Therefore, gut problems could be important for estimating future liver inflammation, while alcoholic liver disease could also provide insight into gut health. Gut problems accompanied by alcoholic liver disease include gut motility and absorption problems, mucosal damage and gut microbiota dysbiosis, and gastrointestinal carcinogenesis...
June 29, 2016: Journal of Digestive Diseases
Behnam Saberi, Alia S Dadabhai, Yoon-Young Jang, Ahmet Gurakar, Esteban Mezey
Alcohol is one of the most common etiologies of liver disease, and alcoholic liver disease overall is the second most common indication for liver transplantation in the United States. It encompasses a spectrum of disease, including fatty liver disease, alcoholic hepatitis (AH), and alcoholic cirrhosis. AH can range from mild to severe disease, with severe disease being defined as: Discriminant Function (DF) ≥ 32, or Model for End-stage Liver Disease (MELD) ≥ 21, or presence of hepatic encephalopathy. Management of the mild disease consists mainly of abstinence and supportive care...
June 28, 2016: Journal of Clinical and Translational Hepatology
S Guercio Nuzio, M Di Stasi, L Pierri, J Troisi, M Poeta, A Bisogno, F Belmonte, M Tripodi, D Di Salvio, G Massa, R Savastano, P Cavallo, M Boffardi, D Ziegenhardt, I Bergheim, C Mandato, P Vajro
BACKGROUND: Gut-liver axis (GLA) dysfunction appears to play a role in obesity and obesity-related hepatic complications. OBJECTIVES: This study sought to concurrently explore several GLA components in a paediatric obese population with/without liver disease. METHODS: Thirty-two children (mean age 11.2 years) were enrolled: nine controls with normal weight and 23 patients with obesity (OB+). Of the 23 patients OB(+), 12 had not steatosis (ST-), and 11 had steatosis (ST+) (associated [n = 8] or not [n = 3] with hypertransaminasaemia [ALT +/-])...
June 28, 2016: Pediatric Obesity
Emina Halilbasic, Claudia Fuchs, Stefan Traussnigg, Michael Trauner
The intracellular nuclear receptor farnesoid X receptor (FXR) and the transmembrane G protein-coupled receptor 5 (TGR5) respond to bile acids (BAs) by activating transcriptional networks and/or signaling cascades. These cascades affect the expression of a great number of target genes relevant for BA, cholesterol, lipid and carbohydrate metabolism, as well as genes involved in inflammation, fibrosis and carcinogenesis. FXR activation in the liver tissue and beyond, such as the gut-liver axis, kidney and adipose tissue, plays a role in metabolic diseases...
2016: Digestive Diseases
Judith Aron-Wisnewsky, Karine Clement, Jean-Louis Pépin
Obstructive sleep apnea (OSA) and more importantly its hallmark, chronic intermittent hypoxia (CIH), are established factors in the pathogenesis and exacerbation of nonalcoholic fatty liver disease (NAFLD). This has been clearly demonstrated in rodent models exposed to intermittent hypoxia, and strong evidence now also exists in both paediatric and adult human populations. OSA and CIH induce insulin-resistance and dyslipidemia which are involved in NAFLD physiopathogenesis. CIH increases the expression of the hypoxia inducible transcription factor HIF1α and that of downstream genes involved in lipogenesis, thereby increasing β-oxidation and consequently exacerbating liver oxidative stress...
August 2016: Metabolism: Clinical and Experimental
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