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bile acid and gut microbiome

M Chondronikola, L L S Harris, S Klein
Type 2 diabetes (T2D) is a major worldwide public health concern. Despite a large armamentarium of T2D medications, a large proportion of patients fail to achieve recommended treatment goals for glycemic control. Weight loss has profound beneficial effects on the metabolic abnormalities involved in the pathogenesis of T2D. Accordingly, bariatric surgery, which is the most effective available weight loss therapy, is also the most effective therapy for treating patients with T2D. Surgical procedures that bypass the upper gastrointestinal (UGI) tract are particularly effective in achieving partial and even complete remission of T2D, suggesting that UGI bypass has weight loss-independent effects on glycemic control...
October 14, 2016: Journal of Internal Medicine
Annefleur M Koopen, Albert K Groen, Max Nieuwdorp
PURPOSE OF REVIEW: The absolute burden of cardiovascular risk remains high despite currently available preventive and therapeutic options. In search for novel therapeutic leads, mounting evidence has linked the gut microbiota as well as their metabolites to the development of cardiometabolic diseases. RECENT FINDINGS: The intestinal microbiota influences the host via different metabolic pathways as inducer of endotoxemia, formation of trimethylamine-N-oxide, production of short chain fatty acids, and is a regulator in intestinal bile acid metabolism...
September 26, 2016: Current Opinion in Lipidology
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
Araceli Muñoz-Garach, Cristina Diaz-Perdigones, Francisco J Tinahones
In recent years, many studies have related gut microbiome to development of highly prevalent diseases such as type 2 diabetes and obesity. Obesity itself is associated to changes in the composition of gut microbiome, with a trend to an overgrowth of microorganisms more efficiently obtaining energy from diet. There are several mechanisms that relate microbiota to the onset of insulin resistance and diabetes, including changes in bowel permeability, endotoxemia, interaction with bile acids, changes in the proportion of brown adipose tissue, and effects associated to use of drugs like metformin...
September 12, 2016: Endocrinología y Nutrición: órgano de la Sociedad Española de Endocrinología y Nutrición
Stavros Bashiardes, Hagit Shapiro, Shachar Rozin, Oren Shibolet, Eran Elinav
BACKGROUND: Non-alcoholic fatty liver (NAFLD) is a common, multi-factorial, and poorly understood liver disease whose incidence is globally rising. NAFLD is generally asymptomatic and associated with other manifestations of the metabolic syndrome. Yet, up to 25% of NAFLD patients develop a progressive inflammatory liver disease termed non-alcoholic steatohepatitis (NASH) that may progress towards cirrhosis, hepatocellular carcinoma, and the need for liver transplantation. In recent years, several lines of evidence suggest that the gut microbiome represents a significant environmental factor contributing to NAFLD development and its progression into NASH...
September 2016: Molecular Metabolism
Lauren K Barron, Christopher P Gayer, Anne Roberts, Jamie M Golden, Bola G Aladegbami, Jun Guo, Christopher R Erwin, Brad W Warner
BACKGROUND: Intestinal failure-associated liver disease causes significant mortality in patients with short bowel syndrome. Steatosis, a major component of intestinal failure-associated liver disease has been shown to persist even after weaning from parenteral nutrition. We sought to determine whether steatosis occurs in our murine model of short bowel syndrome and whether steatosis was affected by manipulation of the intestinal microbiome. METHODS: Male C57BL6 mice underwent 50% small bowel resection and orogastric gavage with vancomycin or vehicle for 10 weeks...
August 31, 2016: Surgery
Steven K Malin, Sangeeta R Kashyap
Bariatric surgery is a gastrointestinal procedure that has emerged as the most effective treatment for weight loss. Roux-en-Y gastric bypass and sleeve gastrectomy are the main procedures currently performed. However, the benefits of bariatric surgery extend beyond weight loss. In fact, improvements in β-cell function occur before clinically meaningful weight loss and contribute to type 2 diabetes mellitus (T2D) remission. Herein, we discuss evidence supporting the efficacy of bariatric surgery for weight loss and improved insulin secretion in patients with and without T2D...
July 2016: Surgery for Obesity and related Diseases: Official Journal of the American Society for Bariatric Surgery
Abigail Basson, Ashley Trotter, Alex Rodriguez-Palacios, Fabio Cominelli
Numerous reviews have discussed gut microbiota composition changes during inflammatory bowel diseases (IBD), particularly Crohn's disease (CD). However, most studies address the observed effects by focusing on studying the univariate connection between disease and dietary-induced alterations to gut microbiota composition. The possibility that these effects may reflect a number of other interconnected (i.e., pantropic) mechanisms, activated in parallel, particularly concerning various bacterial metabolites, is in the process of being elucidated...
2016: Frontiers in Immunology
Maryam Goudarzi, Tytus D Mak, Jonathan P Jacobs, Bo-Hyun Moon, Steven J Strawn, Jonathan Braun, David J Brenner, Albert J Fornace, Heng-Hong Li
Medical responders to radiological and nuclear disasters currently lack sufficient high-throughput and minimally invasive biodosimetry tools to assess exposure and injury in the affected populations. For this reason, we have focused on developing robust radiation exposure biomarkers in easily accessible biofluids such as urine, serum and feces. While we have previously reported on urine and serum biomarkers, here we assessed perturbations in the fecal metabolome resulting from exposure to external X radiation in vivo...
September 2016: Radiation Research
Ajay Kumar Jain, Abhineet Sharma, Sumit Arora, Keith Blomenkamp, Ik Chan Jun, Robert Luong, David John Westrich, Aayush Mittal, Paula M Buchanan, Miguel A Guzman, John Long, Brent A Neuschwander-Tetri, Jeffery Teckman
BACKGROUND: Parenteral nutrition (PN) is a lifesaving therapy but is associated with gut atrophy and cholestasis. While bile acids (BAs) can modulate intestinal growth via gut receptors, the gut microbiome likely influences gut proliferation and inflammation. BAs also regulate the bile salt export pump (BSEP) involved in cholestasis. We hypothesized that the BA receptor agonist oleanolic acid (OA) regulates gut TGR5 receptor and modulates gut microbiota to prevent PN-associated injury...
August 8, 2016: JPEN. Journal of Parenteral and Enteral Nutrition
Vinod S Hegade, Stuart F W Kendrick, Robert L Dobbins, Sam R Miller, Duncan Richards, James Storey, George Dukes, Kim Gilchrist, Susan Vallow, Graeme J Alexander, Margaret Corrigan, Gideon M Hirschfield, David E J Jones
BACKGROUND: Pruritus (itch) is a symptom commonly experienced by patients with cholestatic liver diseases such as primary biliary cholangitis (PBC, previously referred to as primary biliary cirrhosis). Bile acids (BAs) have been proposed as potential pruritogens in PBC. The ileal bile acid transporter (IBAT) protein expressed in the distal ileum plays a key role in the enterohepatic circulation of BAs. Pharmacological inhibition of IBAT with GSK2330672 may reduce BA levels in the systemic circulation and improve pruritus...
2016: BMC Gastroenterology
Richard D Semba, Marta Gonzalez-Freire, Ruin Moaddel, Indi Trehan, Kenneth M Maleta, Mohammed Khadeer, M Isabel Ordiz, Luigi Ferrucci, Mark J Manary
OBJECTIVES: Environmental enteric dysfunction (EED), a clinically asymptomatic condition characterized by inflammation of the small bowel mucosa, villous atrophy, and increased gut permeability, is common among children in developing countries. Because of abnormal gut mucosa and altered gut microbiome, EED could potentially affect the metabolism and enterohepatic circulation of bile acids. METHODS: In 313 children, aged 12-59 months, EED was assessed by the dual sugar absorption test...
June 17, 2016: Journal of Pediatric Gastroenterology and Nutrition
Marika Ziętak, Petia Kovatcheva-Datchary, Lidia H Markiewicz, Marcus Ståhlman, Leslie P Kozak, Fredrik Bäckhed
Maintenance of body temperature in cold-exposed animals requires induction of thermogenesis and management of fuel. Here, we demonstrated that reducing ambient temperature attenuated diet-induced obesity (DIO), which was associated with increased iBAT thermogenesis and a plasma bile acid profile similar to that of germ-free mice. We observed a marked shift in the microbiome composition at the phylum and family levels within 1 day of acute cold exposure and after 4 weeks at 12°C. Gut microbiota was characterized by increased levels of Adlercreutzia, Mogibacteriaceae, Ruminococcaceae, and Desulfovibrio and reduced levels of Bacilli, Erysipelotrichaceae, and the genus rc4-4...
June 14, 2016: Cell Metabolism
Cecilia Noecker, Alexander Eng, Sujatha Srinivasan, Casey M Theriot, Vincent B Young, Janet K Jansson, David N Fredricks, Elhanan Borenstein
: Multiple molecular assays now enable high-throughput profiling of the ecology, metabolic capacity, and activity of the human microbiome. However, to date, analyses of such multi-omic data typically focus on statistical associations, often ignoring extensive prior knowledge of the mechanisms linking these various facets of the microbiome. Here, we introduce a comprehensive framework to systematically link variation in metabolomic data with community composition by utilizing taxonomic, genomic, and metabolic information...
January 2016: MSystems
Vance L Albaugh, C Robb Flynn, Robyn A Tamboli, Naji N Abumrad
Obesity and its associated medical conditions continue to increase and add significant burden to patients, as well as health-care systems, worldwide. Bariatric surgery is the most effective treatment for severe obesity and its comorbidities, and resolution of diabetes is weight loss-independent in the case of some operations. Although these weight-independent effects are frequently described clinically, the mechanisms behind them are not well understood and remain an intense area of focus in the growing field of metabolic and bariatric surgery...
2016: F1000Research
Rachel L Batterham, David E Cummings
More than 20 years ago, Pories et al. published a seminal article, "Who Would Have Thought It? An Operation Proves to Be the Most Effective Therapy for Adult-Onset Diabetes Mellitus." This was based on their observation that bariatric surgery rapidly normalized blood glucose levels in obese people with type 2 diabetes mellitus (T2DM), and 10 years later, almost 90% remained diabetes free. Pories et al. suggested that caloric restriction played a key role and that the relative contributions of proximal intestinal nutrient exclusion, rapid distal gut nutrient delivery, and the role of gut hormones required further investigation...
June 2016: Diabetes Care
Ralf Weiskirchen, Frank Tacke
Chronic liver injury is accompanied by a dysbalanced scarring process, termed fibrosis. This process is mainly driven by chronic inflammation and an altered activity of a multitude of different chemokines and cytokines, resulting in the infiltration by immune cells (especially macrophages) and increase of matrix-expressing cell types. These processes might lead to cirrhosis representing the end-stage of fibrosis. Recent clinical studies comprising patients successfully treated for viral hepatitis showed that liver fibrogenesis and even cirrhosis may be reverted...
2016: Digestive Diseases
Fuzhou Xu, Fangfang Guo, Xiao Jian Hu, Jun Lin
Bile salt hydrolase (BSH) is a gut-bacterial enzyme that negatively influences host fat digestion and energy harvesting. The BSH enzyme activity functions as a gateway reaction in the small intestine by the deconjugation of glycine-conjugated or taurine-conjugated bile acids. Extensive gut-microbiota studies have suggested that BSH is a key mechanistic microbiome target for the development of novel non-antibiotic food additives to improve animal feed production and for the design of new measures to control obesity in humans...
May 2016: Acta Crystallographica. Section F, Structural Biology Communications
Jerome Boursier, Anna Mae Diehl
Recent progress has allowed a more comprehensive study of the gut microbiota. Gut microbiota helps in health maintenance and gut dysbiosis associates with chronic metabolic diseases. Modulation of short-chain fatty acids and choline bioavailability, lipoprotein lipase induction, alteration of bile acid profile, endogenous alcohol production, or liver inflammation secondary to endotoxemia result from gut dysbiosis. Modulation of the gut microbiota by pre/probiotics gives promising results in animal, but needs to be evaluated in human before use in clinical practice...
May 2016: Clinics in Liver Disease
A E Morgan, K M Mooney, S J Wilkinson, N A Pickles, M T Mc Auley
Cholesterol plays a vital role in the human body as a precursor of steroid hormones and bile acids, in addition to providing structure to cell membranes. Whole body cholesterol metabolism is maintained by a highly coordinated balancing act between cholesterol ingestion, synthesis, absorption, and excretion. The aim of this review is to discuss how ageing interacts with these processes. Firstly, we will present an overview of cholesterol metabolism. Following this, we discuss how the biological mechanisms which underpin cholesterol metabolism are effected by ageing...
May 2016: Ageing Research Reviews
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