Gut-liver axis at the frontier of host-microbial interactions
Liver and intestine are tightly linked through the venous system of the portal circulation. Consequently, the liver is the primary recipient of gut-derived products, most prominently dietary nutrients and microbial components. It functions as a secondary "firewall" and protects the body from intestinal pathogens and other microbial products that have crossed the primary barrier of the intestinal tract. Disruption of the intestinal barrier enhances microbial exposure of the liver, which can have detrimental or beneficial effects in the organ depending on the specific circumstances. Conversely, the liver also exerts influenc...
Source: AJP: Gastrointestinal and Liver Physiology - May 1, 2017 Category: Gastroenterology Authors: Brandl, K., Kumar, V., Eckmann, L. Tags: MINI-REVIEW Source Type: research

Rationale for the use of statins in liver disease
The evolution of chronic liver injuries from benign and manageable dysfunction to life threatening end-stage liver disease with severe complications renders chronic liver disease a global health burden. Because of the lack of effective medication, transplantation remains the only and final curative option for end-stage liver disease. Since the demand for organ transplants by far exceeds the supply, other treatment options are urgently required to prevent progression and improve end-stage liver disease. Statins are primarily cholesterol-lowering drugs used for primary or secondary prevention of cardiovascular diseases. In a...
Source: AJP: Gastrointestinal and Liver Physiology - May 1, 2017 Category: Gastroenterology Authors: Schierwagen, R., Uschner, F. E., Magdaleno, F., Klein, S., Trebicka, J. Tags: MINI-REVIEW Source Type: research

Corrigendum
(Source: AJP: Gastrointestinal and Liver Physiology)
Source: AJP: Gastrointestinal and Liver Physiology - April 5, 2017 Category: Gastroenterology Tags: CORRIGENDUM Source Type: research

Synergy of glucagon-like peptide-2 and epidermal growth factor coadministration on intestinal adaptation in neonatal piglets with short bowel syndrome
Glucagon-like peptide-2 (GLP-2) and epidermal growth factor (EGF) treatment enhance intestinal adaptation. To determine whether these growth factors exert synergistic effects on intestinal growth and function, GLP-2 and EGF-containing media (EGF-cm) were administered, alone and in combination, in neonatal piglet models of short bowel syndrome (SBS). Neonatal Landrace-Large White piglets were block randomized to 75% midintestinal [jejunoileal (JI) group] or distal intestinal [jejunocolic (JC) group] resection or sham control, with 7-day infusion of saline (control), intravenous human GLP-2 (11 nmol·kg–1·...
Source: AJP: Gastrointestinal and Liver Physiology - April 5, 2017 Category: Gastroenterology Authors: Lim, D. W., Levesque, C. L., Vine, D. F., Muto, M., Koepke, J. R., Nation, P. N., Wizzard, P. R., Li, J., Bigam, D. L., Brubaker, P. L., Turner, J. M., Wales, P. W. Tags: RESEARCH ARTICLE Source Type: research

Nitric oxide regulates homeoprotein OTX1 and OTX2 expression in the rat myenteric plexus after intestinal ischemia-reperfusion injury
Neuronal and inducible nitric oxide synthase (nNOS and iNOS) play a protective and damaging role, respectively, on the intestinal neuromuscular function after ischemia-reperfusion (I/R) injury. To uncover the molecular pathways underlying this dichotomy we investigated their possible correlation with the orthodenticle homeobox proteins OTX1 and OTX2 in the rat small intestine myenteric plexus after in vivo I/R. Homeobox genes are fundamental for the regulation of the gut wall homeostasis both during development and in pathological conditions (inflammation, cancer). I/R injury was induced by temporary clamping the superior ...
Source: AJP: Gastrointestinal and Liver Physiology - April 5, 2017 Category: Gastroenterology Authors: Filpa, V., Carpanese, E., Marchet, S., Pirrone, C., Conti, A., Rainero, A., Moro, E., Chiaravalli, A. M., Zucchi, I., Moriondo, A., Negrini, D., Crema, F., Frigo, G., Giaroni, C., Porta, G. Tags: RESEARCH ARTICLE Source Type: research

Involvement of gut microbiota in association between GLP-1/GLP-1 receptor expression and gastrointestinal motility
We examined how gut microbiota affects the link between GLP-1/GLP-1 receptor (GLP-1R) expression and motility of the GI tract. Germ-free (GF) mice (6 wk old) were orally administered a fecal bacterial suspension prepared from specific pathogen-free (SPF) mice, and then after fecal transplantation (FT) GI tissues were obtained from the GF mice at various time points. The expression of GLP-1 and its receptor was examined by immunohistochemistry, and gastrointestinal transit time (GITT) was measured by administration of carmine red solution. GLP-1 was expressed in endocrine cells in the colonic mucosa, and GLP-1R was expresse...
Source: AJP: Gastrointestinal and Liver Physiology - April 5, 2017 Category: Gastroenterology Authors: Yang, M., Fukui, H., Eda, H., Xu, X., Kitayama, Y., Hara, K., Kodani, M., Tomita, T., Oshima, T., Watari, J., Miwa, H. Tags: RESEARCH ARTICLE Source Type: research

Intestinal phosphate absorption is mediated by multiple transport systems in rats
Apical inorganic phosphate (Pi) transport in the small intestine seems to be mainly mediated by the sodium/Pi cotransporter NaPi2b. To verify this role, we have studied the combined effects of pH, phosphonoformate, and Pi deprivation on intestinal Pi transport. Rats were fed, ad libitum, three fodders containing 1.2, 0.6, or 0.1% Pi for 1, 5, or 10 days. Pi deprivation (0.1%) increased both sodium-activated and sodium-independent Pi transport in brush-border membrane vesicles from the duodenum and jejunum for all three times. Alkaline pH inhibited Pi transport, despite the increasing concentration of HPO42– (NaPi2b s...
Source: AJP: Gastrointestinal and Liver Physiology - April 5, 2017 Category: Gastroenterology Authors: Candeal, E., Caldas, Y. A., Guillen, N., Levi, M., Sorribas, V. Tags: RESEARCH ARTICLE Source Type: research

Cell therapy for GI motility disorders: comparison of cell sources and proposed steps for treating Hirschsprung disease
Cell therapeutic approaches to treat a range of congenital and degenerative neuropathies are under intense investigation. There have been recent significant advancements in the development of cell therapy to treat disorders of the enteric nervous system (ENS), enteric neuropathies. These advances include the efficient generation of enteric neural progenitors from pluripotent stem cells and the rescue of a Hirschsprung disease model mouse following their transplantation into the bowel. Furthermore, a recent study provides evidence of functional innervation of the bowel muscle by neurons derived from transplanted ENS-derived...
Source: AJP: Gastrointestinal and Liver Physiology - April 5, 2017 Category: Gastroenterology Authors: Stamp, L. A. Tags: MINI-REVIEW Source Type: research

Molecular mechanism(s) involved in differential expression of vitamin C transporters along the intestinal tract
Mammalian cells utilize two transporters for the uptake of ascorbic acid (AA), Na+-dependent vitamin C transporter SVCT-1 and SVCT-2. In the intestine, these transporters are involved in AA absorption and are expressed at the apical and basolateral membrane domains of the polarized epithelia, respectively. Little is known about the differential expression of these two transporters along the anterior-posterior axis of the intestinal tract and the molecular mechanism(s) that dictate this pattern of expression. We used mouse and human intestinal cDNAs to address these issues. The results showed a significantly lower rate of c...
Source: AJP: Gastrointestinal and Liver Physiology - April 1, 2017 Category: Gastroenterology Authors: Subramanian, V. S., Srinivasan, P., Wildman, A. J., Marchant, J. S., Said, H. M. Tags: RESEARCH ARTICLE Source Type: research

Gut microbiota differs between children with Inflammatory Bowel Disease and healthy siblings in taxonomic and functional composition: a metagenomic analysis
Current treatment for pediatric inflammatory bowel disease (IBD) patients is often ineffective, with serious side effects. Manipulating the gut microbiota via fecal microbiota transplantation (FMT) is an emerging treatment approach but remains controversial. We aimed to assess the composition of the fecal microbiome through a comparison of pediatric IBD patients to their healthy siblings, evaluating risks and prospects for FMT in this setting. A case-control (sibling) study was conducted analyzing fecal samples of six children with Crohn’s disease (CD), six children with ulcerative colitis (UC) and 12 healthy sibling...
Source: AJP: Gastrointestinal and Liver Physiology - April 1, 2017 Category: Gastroenterology Authors: Knoll, R. L., Forslund, K., Kultima, J. R., Meyer, C. U., Kullmer, U., Sunagawa, S., Bork, P., Gehring, S. Tags: RESEARCH ARTICLE Source Type: research

RCAD/BiP pathway is necessary for the proper synthesis of digestive enzymes and secretory function of the exocrine pancreas
In conclusion, the RCAD/BiP pathway is required for proper synthesis and secretion of pancreatic enzymes. In alcoholism, increased levels of components of the Ufm1 system could prevent the deleterious effects of alcohol in the pancreas by regulating BiP levels. NEW & NOTEWORTHY RCAD/BiP pathway is required for the proper synthesis and secretion of amylase from pancreatic acini, as well as for the maintenance of the ER homeostasis. In alcoholism, the exocrine pancreas could increase the levels of components of the Ufm1 system to protect itself from alcohol's deleterious effects by regulating the expression of ER chapero...
Source: AJP: Gastrointestinal and Liver Physiology - March 9, 2017 Category: Gastroenterology Authors: Miller, C., Cai, Y., Patton, T., Graves, S. H., Li, H., Sabbatini, M. E. Tags: RESEARCH ARTICLE Source Type: research

Inhibition of sphingosine 1-phosphate signaling ameliorates murine nonalcoholic steatohepatitis
This study describes the use of FTY720, a novel small molecule, for the amelioration of NASH in a mouse model. We demonstrate that 2-wk administration of FTY720 to mice with NASH led to a reduction in liver injury, inflammation, and fibrosis. These data provide a preclinical rationale for studying this drug in human NASH. (Source: AJP: Gastrointestinal and Liver Physiology)
Source: AJP: Gastrointestinal and Liver Physiology - March 9, 2017 Category: Gastroenterology Authors: Mauer, A. S., Hirsova, P., Maiers, J. L., Shah, V. H., Malhi, H. Tags: RESEARCH ARTICLE Source Type: research

Hepatocyte-specific PPARA expression exclusively promotes agonist-induced cell proliferation without influence from nonparenchymal cells
Peroxisome proliferator-activated receptor-α (PPARA) is a nuclear transcription factor and key mediator of systemic lipid metabolism. Prolonged activation in rodents causes hepatocyte proliferation and hepatocellular carcinoma. Little is known about the contribution of nonparenchymal cells (NPCs) to PPARA-mediated cell proliferation. NPC contribution to PPARA agonist-induced hepatomegaly was assessed in hepatocyte (PparaHep)- and macrophage (PparaMac)-specific Ppara null mice. Mice were treated with the agonist Wy-14643 for 14 days, and response of conditional null mice was compared with conventional knockout mice (P...
Source: AJP: Gastrointestinal and Liver Physiology - March 9, 2017 Category: Gastroenterology Authors: Brocker, C. N., Yue, J., Kim, D., Qu, A., Bonzo, J. A., Gonzalez, F. J. Tags: RESEARCH ARTICLE Source Type: research

Enteric glia cells are critical to limiting the intestinal inflammatory response after injury
Vagal nerve stimulation (VNS) has been shown to limit intestinal inflammation following injury; however, a direct connection between vagal terminals and resident intestinal immune cells has yet to be identified. We have previously shown that enteric glia cell (EGC) expression is increased after injury through a vagal-mediated pathway to help restore gut barrier function. We hypothesize that EGCs modulate immune cell recruitment following injury and relay vagal anti-inflammatory signals to resident immune cells in the gut. EGCs were selectively ablated from an isolated segment of distal bowel with topical application of ben...
Source: AJP: Gastrointestinal and Liver Physiology - March 9, 2017 Category: Gastroenterology Authors: Langness, S., Kojima, M., Coimbra, R., Eliceiri, B. P., Costantini, T. W. Tags: RESEARCH ARTICLE Source Type: research

PKC{beta}: Expanding role in hepatic adaptation of cholesterol homeostasis to dietary fat/cholesterol
Cholesterol homeostasis relies on an intricate network of cellular processes whose deregulation in response to Western type high-fat/cholesterol diets can lead to several life-threatening pathologies. Significant advances have been made in resolving the molecular identity and regulatory function of transcription factors sensitive to fat, cholesterol, or bile acids, but whether body senses the presence of both fat and cholesterol simultaneously is not known. Assessing the impact of a high-fat/cholesterol load, rather than an individual component alone, on cholesterol homeostasis is more physiologically relevant because West...
Source: AJP: Gastrointestinal and Liver Physiology - March 9, 2017 Category: Gastroenterology Authors: Mehta, D., Mehta, K. D. Tags: MINI-REVIEW Source Type: research