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Short gut

Hitoshi Ono, Yasunari Kojima, Hiroshi Harada, Yoshikazu Abe, Takuro Endo, Mamoru Kobayashi
1. The pharmacokinetic and metabolite profiles of mizagliflozin, a novel selective sodium glucose co-transporter 1 inhibitor designed to act only in the intestine, were investigated in rats. 2. Mizagliflozin administrated intravenously (0.3 mg/kg) and orally (3 mg/kg) declined with a short half-life (0.23 and 1.14 h, respectively). The absolute bioavailability was only 0.02%. Following intravenous administration of [14 C]mizagliflozin (0.3 mg/kg), radioactivity in plasma was also rapidly declined. Up to 24 h after oral administration of [14 C]mizagliflozin (1 mg/kg), radioactivity was recovered in the faeces (98...
March 20, 2018: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
Sunmin Park, Da Sol Kim, Eun Seon Kang, Da Bin Kim, Suna Kang
We evaluated the effects of intracerebroventricular administration(ICV) of brain estrogen and progesterone on menopausal symptoms and their effects on the secretion of follicle-stimulating hormone(FSH) and luteinizing hormone(LH) in estrogen-deficient rats. Three weeks after ovariectomy(OVX) or Sham-operation, OVX rats were given ICV infusions of either 17β-estradiol(4 μg/day; ICV-E), progesterone(0.8 μg/day; ICV-P), or vehicle(control) for 4 weeks. OVX rats in the positive-control group were orally provided 150 μg 17β-estradiol/kg bw/day...
March 20, 2018: American Journal of Physiology. Endocrinology and Metabolism
Casey M Theriot
Over the past 10 years, microbiome research has focused on defining the structures associated with different disease states in multiple systems, but has fallen short on showing causation. Prior omic studies have generated many new hypotheses, but moving forward we need to start dissecting the function of each bacterium alone and in concert with complex bacterial communities in well-characterized systems. Over the next 5 years, we need a merging of new omic technologies for exploratory studies with classical bacterial genetics, bacterial physiology, protein engineering, and biochemistry to further define the biochemical mechanisms of the gut microbiota...
March 2018: MSystems
Bastian Hornung, Vitor A P Martins Dos Santos, Hauke Smidt, Peter J Schaap
Humans are not autonomous entities. We are all living in a complex environment, interacting not only with our peers, but as true holobionts; we are also very much in interaction with our coexisting microbial ecosystems living on and especially within us, in the intestine. Intestinal microorganisms, often collectively referred to as intestinal microbiota, contribute significantly to our daily energy uptake by breaking down complex carbohydrates into simple sugars, which are fermented to short-chain fatty acids and subsequently absorbed by human cells...
2018: Genes & Nutrition
Melanie Tramontano, Sergej Andrejev, Mihaela Pruteanu, Martina Klünemann, Michael Kuhn, Marco Galardini, Paula Jouhten, Aleksej Zelezniak, Georg Zeller, Peer Bork, Athanasios Typas, Kiran Raosaheb Patil
Bacterial metabolism plays a fundamental role in gut microbiota ecology and host-microbiome interactions. Yet the metabolic capabilities of most gut bacteria have remained unknown. Here we report growth characteristics of 96 phylogenetically diverse gut bacterial strains across 4 rich and 15 defined media. The vast majority of strains (76) grow in at least one defined medium, enabling accurate assessment of their biosynthetic capabilities. These do not necessarily match phylogenetic similarity, thus indicating a complex evolution of nutritional preferences...
March 19, 2018: Nature Microbiology
Renata N Florindo, Valquiria P Souza, Lívia R Manzine, Cesar M Camilo, Sandro R Marana, Igor Polikarpov, Alessandro S Nascimento
Bifidobacterium is an important genus of probiotic bacteria colonizing the human gut. These bacteria can uptake oligosaccharides for the fermentative metabolism of hexoses and pentoses, producing lactate, acetate as well as short-chain fatty acids and propionate. These end-products are known to have important effects on human health. β-glucosidases (EC are pivotal enzymes for the metabolism and homeostasis of Bifidobacterium, since they hydrolyze small and soluble saccharides, typically producing glucose...
March 16, 2018: Biochimie
Rekha Seshadri, Sinead C Leahy, Graeme T Attwood, Koon Hoong Teh, Suzanne C Lambie, Adrian L Cookson, Emiley A Eloe-Fadrosh, Georgios A Pavlopoulos, Michalis Hadjithomas, Neha J Varghese, David Paez-Espino, Rechelle Perry, Gemma Henderson, Christopher J Creevey, Nicolas Terrapon, Pascal Lapebie, Elodie Drula, Vincent Lombard, Edward Rubin, Nikos C Kyrpides, Bernard Henrissat, Tanja Woyke, Natalia N Ivanova, William J Kelly
Productivity of ruminant livestock depends on the rumen microbiota, which ferment indigestible plant polysaccharides into nutrients used for growth. Understanding the functions carried out by the rumen microbiota is important for reducing greenhouse gas production by ruminants and for developing biofuels from lignocellulose. We present 410 cultured bacteria and archaea, together with their reference genomes, representing every cultivated rumen-associated archaeal and bacterial family. We evaluate polysaccharide degradation, short-chain fatty acid production and methanogenesis pathways, and assign specific taxa to functions...
March 19, 2018: Nature Biotechnology
Lin Hai Kurahara, Keizo Hiraishi, Yaopeng Hu, Kaori Koga, Miki Onitsuka, Mayumi Doi, Kunihiko Aoyagi, Hidetoshi Takedatsu, Daibo Kojima, Yoshitaka Fujihara, Yuwen Jian, Ryuji Inoue
Background & Aims: The transient receptor potential ankyrin 1 (TRPA1) channel is highly expressed in the intestinal lamina propria, but its contribution to gut physiology/pathophysiology is unclear. Here, we evaluated the function of myofibroblast TRPA1 channels in intestinal remodeling. Methods: An intestinal myofibroblast cell line (InMyoFibs) was stimulated by transforming growth factor-β1 to induce in vitro fibrosis. Trpa1 knockout mice were generated using the Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) system...
March 2018: Cellular and Molecular Gastroenterology and Hepatology
Neha M Sahasrabudhe, Martin Beukema, Lingmin Tian, Berit Troost, Jan Scholte, Erik Bruininx, Geert Bruggeman, Marco van den Berg, Anton Scheurink, Henk A Schols, Marijke M Faas, Paul de Vos
Dietary carbohydrate fibers are known to prevent immunological diseases common in Western countries such as allergy and asthma but the underlying mechanisms are largely unknown. Until now beneficial effects of dietary fibers are mainly attributed to fermentation products of the fibers such as anti-inflammatory short-chain fatty acids (SCFAs). Here, we found and present a new mechanism by which dietary fibers can be anti-inflammatory: a commonly consumed fiber, pectin, blocks innate immune receptors. We show that pectin binds and inhibits, toll-like receptor 2 (TLR2) and specifically inhibits the proinflammatory TLR2-TLR1 pathway while the tolerogenic TLR2-TLR6 pathway remains unaltered...
2018: Frontiers in Immunology
Naif O Al-Harbi, Ahmed Nadeem, Sheikh F Ahmad, Moureq R Alotaibi, Abdullah F AlAsmari, Wael A Alanazi, Mohammad M Al-Harbi, Ahmad M El-Sherbeeny, Khalid E Ibrahim
Sepsis affects millions of people worldwide and is associated with acute kidney injury (AKI). Innate and adaptive immune cells have been shown to play an important role in AKI through release of various inflammatory mediators which include reactive oxidant species (ROS). Acetate, a short chain fatty acid produced by gut bacteria has anti-inflammatory properties and has also been shown to modulate oxidative stress in different immune cells. Effects of acetate have been shown to be both GPR43 dependent and independent in different cells/tissues...
March 12, 2018: International Immunopharmacology
Jianping Quan, Gengyuan Cai, Jian Ye, Ming Yang, Rongrong Ding, Xingwang Wang, Enqin Zheng, Disheng Fu, Shaoyun Li, Shenping Zhou, Dewu Liu, Jie Yang, Zhenfang Wu
In an attempt to increase profits and sustainability in the swine industry, the gut microbiome has become a focus of much research. In this study, we performed a comparative analysis of the gut microbiome in the ileum, cecum, and colon of Duroc × (Landrace × Yorkshire) (DLY) pigs showing two extreme feed conversion ratios (FCRs) using 16S rRNA gene sequencing. The results revealed that the microbial community in the cecum and colon had significantly higher alpha diversity than the ileum. We further identified 11, 55, and 55 operational taxonomic units (OTUs) with significantly different relative abundances between the high and low FCR pigs among the three gut locations, respectively...
March 14, 2018: Scientific Reports
Pernille Wismann, Søren L Pedersen, Gitte Hansen, Karin Mannerstedt, Philip J Pedersen, Palle B Jeppesen, Niels Vrang, Keld Fosgerau, Jacob Jelsing
AIM: Analogues of several gastrointestinal peptide hormones have been developed into effective medicines for treatment of diseases such as type 2 diabetes mellitus (T2DM), obesity and short bowel syndrome (SBS). In this study, we aimed to explore whether the combination of glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2) into a potent co-agonist could provide additional benefits compared to existing monotherapies. METHODS: A short-acting (GUB09-123) and a half-life extended (GUB09-145) GLP-1/GLP-2 co-agonist were generated using solid-phase peptide synthesis and tested for effects on food intake, body weight, glucose homeostasis, and gut proliferation in lean mice and in diabetic db/db mice...
March 11, 2018: Physiology & Behavior
Kevin Rey, Sukhbir Manku, Winnie Enns, Thea Van Rossum, Kevin Bushell, Ryan D Morin, Fiona S L Brinkman, Jonathan C Choy
BACKGROUND: The gut microbiota influences many immunological processes but how its disruption affects transplant rejection is poorly understood. METHODS: Interposition grafting of aortic segments was used to examine vascular rejection. The gut microbiota was disrupted in graft recipients using an antibiotic cocktail (ampicillin, vancomycin, metronidazole, neomycin sulfate) in their drinking water. RESULTS: Treatment of mice with antibiotics severely reduced total bacterial content in the intestine and disrupted the bacterial composition...
March 10, 2018: Transplantation
Phoebe Lin
PURPOSE OF REVIEW: The intestinal commensal microbiota are important in shaping immune cell repertoire and are influenced by host genetics. Because of this intricate interaction, an intestinal dysbiosis has been associated with multiple immune-mediated polygenic diseases. This review summarizes the literature on how alterations in the intestinal microbiota contribute to immune-mediated ocular disease, and how to potentially target the gut microbiome for therapeutic benefit. RECENT FINDINGS: Several groups have demonstrated the importance of the intestinal microbiome in uveitis pathogenesis...
March 13, 2018: Current Opinion in Ophthalmology
Diego Moreno-Pérez, Carlo Bressa, María Bailén, Safa Hamed-Bousdar, Fernando Naclerio, Manuel Carmona, Margarita Pérez, Rocío González-Soltero, Maria Gregoria Montalvo-Lominchar, Claudia Carabaña, Mar Larrosa
Nutritional supplements are popular among athletes to improve performance and physical recovery. Protein supplements fulfill this function by improving performance and increasing muscle mass; however, their effect on other organs or systems is less well known. Diet alterations can induce gut microbiota imbalance, with beneficial or deleterious consequences for the host. To test this, we performed a randomized pilot study in cross-country runners whose diets were complemented with a protein supplement (whey isolate and beef hydrolysate) ( n = 12) or maltodextrin (control) ( n = 12) for 10 weeks...
March 10, 2018: Nutrients
Geneviève Huard, M Isabel Fiel, Jang Moon, Kishore Iyer, Thomas D Schiano
INTRODUCTION: Intestinal failure-associated liver disease (IFALD) occurs commonly in intestinal transplant (ITx) candidates receiving parenteral nutrition (PN). The aim of this study is to establish the prevalence and risk factors for advanced liver fibrosis in adults at the time of ITx. METHODS: Retrospective chart review of all ITx was performed in adults between January 2000 and May 2014. Advanced liver fibrosis was defined as stage 3 or stage 4 fibrosis. RESULTS: Fifty-three patients met the inclusion criteria...
March 13, 2018: JPEN. Journal of Parenteral and Enteral Nutrition
Sophie A Poeker, Annelies Geirnaert, Laura Berchtold, Anna Greppi, Lukasz Krych, Robert E Steinert, Tomas de Wouters, Christophe Lacroix
Consumption of fermentable dietary fibers (DFs), which can induce growth and/or activity of specific beneficial populations, is suggested a promising strategy to modulate the gut microbiota and restore health in microbiota-linked diseases. Until today, inulin and fructo-oligosaccharides (FOS) are the best studied DFs, while little is known about the gut microbiota-modulating effects of β-glucan, α-galactooligosaccharide (α-GOS) and xylo-oligosaccharide (XOS). Here, we used three continuous in vitro fermentation PolyFermS model to study the modulating effect of these DFs on two distinct human adult proximal colon microbiota, independently from the host...
March 12, 2018: Scientific Reports
Youngji Cho, Galeb Abu-Ali, Hiroki Tashiro, David I Kasahara, Traci A Brown, Jeffrey D Brand, Joel A Mathews, Curtis Huttenhower, Stephanie A Shore
Previous reports demonstrate that the microbiome impacts allergic airway responses, including airway hyperresponsiveness, a characteristic feature of asthma. Here we examined the role of the microbiome in pulmonary responses to a non-allergic asthma trigger, ozone. We depleted the microbiota of conventional mice with either a single antibiotic (ampicillin, metronidazole, neomycin, or vancomycin) or a cocktail of all four antibiotics given via the drinking water. Mice were then exposed to room air or ozone. In air-exposed mice, airway responsiveness was not different in antibiotic- versus control water-treated mice...
March 12, 2018: American Journal of Respiratory Cell and Molecular Biology
Anna Maikova, Johann Peltier, Pierre Boudry, Eliane Hajnsdorf, Nicolas Kint, Marc Monot, Isabelle Poquet, Isabelle Martin-Verstraete, Bruno Dupuy, Olga Soutourina
Clostridium difficile, a major human enteropathogen, must cope with foreign DNA invaders and multiple stress factors inside the host. We have recently provided an experimental evidence of defensive function of the C. difficile CRISPR (clustered regularly interspaced short palindromic repeats)-Cas (CRISPR-associated) system important for its survival within phage-rich gut communities. Here, we describe the identification of type I toxin-antitoxin (TA) systems with the first functional antisense RNAs in this pathogen...
February 26, 2018: Nucleic Acids Research
Lingxiao Gong, Wenyan Cao, Jie Gao, Jing Wang, Huijuan Zhang, Baoguo Sun, Meng Yin
The gut microbiota has recently become a new route for research at the intersection of diet and human health. The aim of this study was to investigate whether whole Tibetan hull-less barley (WHB) and refined Tibetan hull-less barley (RHB) caused differentiation of the fecal microbiota in vitro. The microbiota-accessible ingredients in the 2 barley samples were studied using an in vitro enzymatic digestion procedure. After in vitro digestion, insoluble dietary fiber, phenolic compounds, proteins, and β-glucans were 93...
March 10, 2018: Journal of Food Science
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