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bile acid and gut microbiome

Laura-Isobel McCall, Anupriya Tripathi, Fernando Vargas, Rob Knight, Pieter C Dorrestein, Jair L Siqueira-Neto
Trypanosoma cruzi parasites are the causative agents of Chagas disease. These parasites infect cardiac and gastrointestinal tissues, leading to local inflammation and tissue damage. Digestive Chagas disease is associated with perturbations in food absorption, intestinal traffic and defecation. However, the impact of T. cruzi infection on the gut microbiota and metabolome have yet to be characterized. In this study, we applied mass spectrometry-based metabolomics and 16S rRNA sequencing to profile infection-associated alterations in fecal bacterial composition and fecal metabolome through the acute-stage and into the chronic stage of infection, in a murine model of Chagas disease...
March 12, 2018: PLoS Neglected Tropical Diseases
Jason W Arnold, Joshua B Simpson, Jeffrey Roach, Jakub Kwintkiewicz, M Andrea Azcarate-Peril
Large-scale microbiome studies have established that most of the diversity contained in the gastrointestinal tract is represented at the strain level; however, exhaustive genomic and physiological characterization of human isolates is still lacking. With increased use of probiotics as interventions for gastrointestinal disorders, genomic and functional characterization of novel microorganisms becomes essential. In this study, we explored the impact of strain-level genomic variability on bacterial physiology of two novel human Lactobacillus rhamnosus strains (AMC143 and AMC010) of probiotic potential in relation to stress resistance...
2018: Frontiers in Microbiology
Preeti Pathak, Xie Cen, Robert G Nichols, Jessica M Ferrell, Shannon Boehme, Kristopher W Krausz, Andrew D Patterson, Frank J Gonzalez, John Y L Chiang
Bile acids activate farnesoid X receptor (FXR) and G protein-coupled bile acid receptor-1 (Gpbar-1, aka TGR5) to regulate bile acid metabolism and glucose and insulin sensitivity. FXR and TGR5 are co-expressed in the enteroendocrine L cells but their roles in integrated regulation of metabolism are not completely understood. We reported recently that activation of FXR induces TGR5 to stimulate glucagon-like peptide-1 (GLP-1) secretion to improve insulin sensitivity and hepatic metabolism. In this study, we used the intestine-restricted FXR agonist fexaramine (FEX) to study the effect of activation of intestinal FXR on the gut microbiome, bile acid metabolism, and FXR and TGR5 signaling...
February 27, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Fuyuan Wang, Jingjing Meng, Li Zhang, Timothy Johnson, Chi Chen, Sabita Roy
Opioid analgesics are frequently prescribed in the United States and worldwide. However, serious comorbidities, such as dependence, tolerance, immunosuppression and gastrointestinal disorders limit their long-term use. In the current study, a morphine-murine model was used to investigate the role of the gut microbiome and metabolome as a potential mechanism contributing to the negative consequences associated with opioid use. Results reveal a significant shift in the gut microbiome and metabolome within one day following morphine treatment compared to that observed after placebo...
February 26, 2018: Scientific Reports
S M B Duarte, J T Stefano, L Miele, F R Ponziani, M Souza-Basqueira, L S R R Okada, F G de Barros Costa, K Toda, D F C Mazo, E C Sabino, F J Carrilho, A Gasbarrini, C P Oliveira
BACKGROUND AND AIM: The aim of the study was to compare the gut microbiomes from obese and lean patients with or without NASH to outline phenotypic differences. METHODS AND RESULTS: We performed a cross-sectional pilot study comprising biopsy-proven NASH patients grouped according to BMI. Microbiome DNA was extracted from stool samples, and PCR amplification was performed using primers for the V4 region of the 16S rRNA gene. The amplicons were sequenced using the Ion PGM Torrent platform, and data were analyzed using QIIME software...
October 26, 2017: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
Li Zhang, Weida Wu, Yuan-Kun Lee, Jingjing Xie, Hongfu Zhang
Pigs are one of the most important economic livestock. Gut microbiota is not only critical to the health but also the production efficiency of pigs. Manipulating gut microbiota relies on the full view of gut microbiome and the understanding of drive forces shaping microbial communities. 16s rDNA sequencing was used to profile microbiota along the longitudinal and radical axes to obtain the topographical map of microbiome in different intestinal compartments in young pigs. Alpha and beta-diversities revealed distinct differences in microbial compositions between the distal ileum and cecum and colon, as well as between the lumen and mucosa...
2018: Frontiers in Microbiology
John P Phelan, F Jerry Reen, Jose A Caparros-Martin, Rosemary O'Connor, Fergal O'Gara
Dietary factors, probiotic agents, aging and antibiotics/medicines impact on gut microbiome composition leading to disturbances in localised microbial populations. The impact can be profound and underlies a plethora of human disorders, including the focus of this review; cancer. Compromised microbiome populations can alter bile acid signalling and produce distinct pathophysiological bile acid profiles. These in turn have been associated with cancer development and progression. Exposure to high levels of bile acids, combined with localised molecular/genome instability leads to the acquisition of bile mediated neoplastic alterations, generating apoptotic resistant proliferation phenotypes...
December 29, 2017: Oncotarget
Tianlu Chen, Yijun You, Guoxiang Xie, Xiaojiao Zheng, Aihua Zhao, Jiajian Liu, Qing Zhao, Shouli Wang, Huang Fengjie, Cynthia Rajani, Chongchong Wang, Shaoqiu Chen, Yan Ni, Herbert Yu, Youping Deng, Xiaoyan Wang, Wei Jia
There is increased appreciation for the diverse roles of the microbiome-gut-brain axis on mammalian growth and health throughout the lifespan. Numerous studies demonstrated that gut microbiome and their metabolites were involved extensively in the communication of brain and gut. Association study of brain metabolome and gut microbiome is an active field offering large amount of information on the interaction of microbiome, brain and gut while data size and complicated hierarchical relationships were the major obstacles...
January 21, 2018: Analytical Chemistry
Hagit Shapiro, Aleksandra A Kolodziejczyk, Daniel Halstuch, Eran Elinav
Bile acids (BAs) are cholesterol-derived metabolites that facilitate the intestinal absorption and transport of dietary lipids. Recently, BAs also emerged as pivotal signaling molecules controlling glucose, lipid, and energy metabolism by binding to the nuclear hormone farnesoid X receptor (FXR) and Takeda G protein receptor 5 (TGR5) in multiple organs, leading to regulation of intestinal incretin secretion, hepatic gluconeogenesis, glycogen synthesis, energy expenditure, inflammation, and gut microbiome configuration...
January 16, 2018: Journal of Experimental Medicine
Sean M Mythen, Saravanan Devendran, Celia Méndez-García, Isaac Cann, Jason M Ridlon
Gut metagenomic sequences provide a rich source of microbial genes, the majority of which are annotated by homology or unknown. Genes and gene pathways that encode enzymes catalyzing biotransformation of host bile acids are important to identify in gut metagenomic sequences due to the importance of bile acids on gut microbiome structure and host physiology. Hydroxysteroid dehydrogenases (HSDH) are pyridine nucleotide-dependent enzymes with stereo-specificity and regio-specificity for bile acid and steroid hydroxyl groups...
January 12, 2018: Applied and Environmental Microbiology
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
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
Spencer C Harris, Saravanan Devendran, João M P Alves, Sean M Mythen, Phillip B Hylemon, Jason M Ridlon
BACKGROUND: The multi-step bile acid 7α-dehydroxylating pathway by which a few species of Clostridium convert host primary bile acids to toxic secondary bile acids is of great importance to gut microbiome structure and host physiology and disease. While genes in the oxidative arm of the 7α-dehydroxylating pathway have been identified, genes in the reductive arm of the pathway are still obscure. METHODS: We identified a candidate flavoprotein-encoding gene predicted to metabolize steroids...
March 2018: Biochimica et Biophysica Acta
Richard R Rodrigues, Renee L Greer, Xiaoxi Dong, Karen N DSouza, Manoj Gurung, Jia Y Wu, Andrey Morgun, Natalia Shulzhenko
The gut microbiome plays an important role in health and disease. Antibiotics are known to alter gut microbiota, yet their effects on glucose tolerance in lean, normoglycemic mice have not been widely investigated. In this study, we aimed to explore mechanisms by which treatment of lean mice with antibiotics (ampicillin, metronidazole, neomycin, vancomycin, or their cocktail) influences the microbiome and glucose metabolism. Specifically, we sought to: (i) study the effects on body weight, fasting glucose, glucose tolerance, and fasting insulin, (ii) examine the changes in expression of key genes of the bile acid and glucose metabolic pathways in the liver and ileum, (iii) identify the shifts in the cecal microbiota, and (iv) infer interactions between gene expression, microbiome, and the metabolic parameters...
2017: Frontiers in Microbiology
John Yl Chiang
Bile acids are derived from cholesterol to facilitate intestinal nutrient absorption and biliary secretion of cholesterol. Recent studies have identified bile acids as signaling molecules that activate nuclear farnesoid X receptor (FXR) and membrane G protein-coupled bile acid receptor-1 (Gpbar-1, also known as TGR5) to maintain metabolic homeostasis and protect liver and other tissues and cells from bile acid toxicity. Bile acid homeostasis is regulated by a complex mechanism of feedback and feedforward regulation that is not completely understood...
2017: F1000Research
Ming Lyu, Yue-Fei Wang, Guan-Wei Fan, Xiao-Ying Wang, Shuang-Yong Xu, Yan Zhu
It has become apparent that gut microbiota is closely associated with cardiometabolic diseases (CMDs), and alteration in microbiome compositions is also linked to the host environment. Next generation sequencing (NGS) has facilitated in-depth studies on the effects of herbal medicine and functional food on gut microbiota. Both herbal medicine and functional food contain fiber, polyphenols and polysaccharides, exerting prebiotics-like activities in the prevention and treatment of CMDs. The administrations of herbal medicine and functional food lead to increased the abundance of phylum Bacteroidetes, and genus Akkermansia, Bifidobacteria, Lactobacillus, Bacteroides and Prevotella , while reducing phylum Firmicutes and Firmicutes/Bacteroidetes ratio in gut...
2017: Frontiers in Microbiology
Michael Alan Glaysher, Aruchuna Mohanaruban, Christina Gabriele Prechtl, Anthony P Goldstone, Alexander Dimitri Miras, Joanne Lord, Navpreet Chhina, Emanuela Falaschetti, Nicholas Andrew Johnson, Werd Al-Najim, Claire Smith, Jia V Li, Mayank Patel, Ahmed R Ahmed, Michael Moore, Neil Poulter, Stephen Bloom, Ara Darzi, Carel Le Roux, James P Byrne, Julian P Teare
INTRODUCTION: The prevalence of obesity and obesity-related diseases, including type 2 diabetes mellitus (T2DM), is increasing. Exclusion of the foregut, as occurs in Roux-en-Y gastric bypass, has a key role in the metabolic improvements that occur following bariatric surgery, which are independent of weight loss. Endoscopically placed duodenal-jejunal bypass sleeve devices, such as the EndoBarrier (GI Dynamics, Lexington, Massachusetts, USA), have been designed to create an impermeable barrier between chyme exiting the stomach and the mucosa of the duodenum and proximal jejunum...
November 15, 2017: BMJ Open
Anirikh Chakrabarti, Mathieu Membrez, Delphine Morin-Rivron, Jay Siddharth, Chieh Jason Chou, Hugues Henry, Stephen Bruce, Sylviane Metairon, Frederic Raymond, Bertrand Betrisey, Carole Loyer, Scott J Parkinson, Mojgan Masoodi
The gut microbiome and lipid metabolism are both recognized as essential components in the maintenance of metabolic health. The mechanisms involved are multifactorial and (especially for microbiome) poorly defined. A strategic approach to investigate the complexity of the microbial influence on lipid metabolism would facilitate determination of relevant molecular mechanisms for microbiome-targeted therapeutics. E. coli is associated with obesity and metabolic syndrome and we used this association in conjunction with gnotobiotic models to investigate the impact of E...
2017: NPJ Systems Biology and Applications
Marion Darnaud, Alexandre Dos Santos, Patrick Gonzalez, Sandrine Augui, Claire Lacoste, Christophe Desterke, Gert De Hertogh, Emma Valentino, Emilie Braun, Jinzi Zheng, Raphael Boisgard, Christel Neut, Laurent Dubuquoy, Franck Chiappini, Didier Samuel, Patricia Lepage, Francesca Guerrieri, Joel Doré, Christian Bréchot, Nicolas Moniaux, Jamila Faivre
BACKGROUND & AIMS: Paneth cell dysfunction causes deficiencies in intestinal C-type lectins and antimicrobial peptides, which leads to dysbiosis of the intestinal microbiota, alters the mucosal barrier, and promotes development of inflammatory bowel diseases. We investigated whether transgenic expression of the human regenerating family member 3 alpha gene (REG3A) alters the fecal microbiota and affects development of colitis in mice. METHODS: We performed studies with C57BL/6 mice that express human regenerating family member 3 alpha (hREG3A) in hepatocytes, via the albumin gene promoter...
November 10, 2017: Gastroenterology
Leyuan Li, Xu Zhang, Zhibin Ning, Janice Mayne, Jasmine I Moore, James Butcher, Cheng-Kang Chiang, David Mack, Alain Stintzi, Daniel Figeys
In vitro culture based approaches are time- and cost-effective solutions for rapidly evaluating the effects of drugs or natural compounds against microbiomes. The nutritional composition of the culture medium is an important determinant for effectively maintaining the gut microbiome in vitro. This study combines orthogonal experimental design and a metaproteomics approach to obtaining functional insights into the effects of different medium components on the microbiome. Our results show that the metaproteomic profile respond differently to medium components, including inorganic salts, bile salts, mucin, and short-chain fatty acids...
November 22, 2017: Journal of Proteome Research
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