Pregnancy and bile acid disorders
During pregnancy, extensive adaptations in maternal metabolic and immunological physiology occur. Consequently, preexisting disease may be exacerbated or attenuated, and new disease susceptibility may be unmasked. Cholestatic diseases, characterized by a supraphysiological raise in bile acid levels, require careful monitoring during pregnancy. This review describes the latest advances in the knowledge of intrahepatic cholestasis of pregnancy (ICP), the most common bile acid disorder specific to pregnancy, with a focus on the disease etiology and potential mechanisms of ICP-associated adverse pregnancy outcomes, including f...
Source: AJP: Gastrointestinal and Liver Physiology - July 1, 2017 Category: Gastroenterology Authors: Pataia, V., Dixon, P. H., Williamson, C. Tags: MINI-REVIEW Source Type: research

Letter to the editor: Treating nonalcoholic fatty liver disease with statins. Are all statins equal?
(Source: AJP: Gastrointestinal and Liver Physiology)
Source: AJP: Gastrointestinal and Liver Physiology - June 8, 2017 Category: Gastroenterology Authors: Athyros, V. G., Katsiki, N., Mikhailidis, D. P. Tags: LETTER TO THE EDITOR Source Type: research

A longitudinal study of whole body, tissue, and cellular physiology in a mouse model of fibrosing NASH with high fidelity to the human condition
This study demonstrates in a first of kind longitudinal analysis, the evolution of nonalcoholic steatohepatitis (NASH) on a fast-food diet-induced model. Key findings include 1) hepatic lipid composition changes in a multiphasic fashion as NASH evolves; 2) insulin resistance precedes hepatic inflammation and fibrosis, answering a longstanding chicken-and-egg question regarding the relationship of insulin resistance to liver histology in NASH; and 3) mitochondrial dysfunction and depletion occur after the histological features of NASH are apparent. (Source: AJP: Gastrointestinal and Liver Physiology)
Source: AJP: Gastrointestinal and Liver Physiology - June 8, 2017 Category: Gastroenterology Authors: Krishnan, A., Abdullah, T. S., Mounajjed, T., Hartono, S., McConico, A., White, T., LeBrasseur, N., Lanza, I., Nair, S., Gores, G., Charlton, M. Tags: RESEARCH ARTICLE Source Type: research

A novel murine model of esophageal nonerosive reflux disease: from inflammation to impairment in mucosal integrity
In this study, we developed a novel murine model of NERD in mice with microscopic inflammation and impairment in the epithelial esophageal barrier. Female Swiss mice were subjected to the following surgical procedure: the transitional region between the forestomach and the glandular portion of the stomach was ligated, and a nontoxic ring was placed around the duodenum near the pylorus. The control group underwent sham surgery. The animals were euthanized at 1, 3, 7, and 14 days after surgery. Survival and body weight were monitored daily. Esophageal wet weight, macroscopic lesion, histopathological alterations, myeloperoxi...
Source: AJP: Gastrointestinal and Liver Physiology - June 8, 2017 Category: Gastroenterology Authors: Silva, R. O., Oliveira, F. F. B., Bingana, R. D., Arruda, M. O., Woodland, P., Lee, C., Souza, M. A. N., Soares, P. M. G., Santos, A. A., Sifrim, D., Souza, M. H. L. P. Tags: RESEARCH ARTICLE Source Type: research

Gastrin induces parathyroid hormone-like hormone expression in gastric parietal cells
In this study we used pharmacologic and genetic mouse models as well as human gastric cancer cell lines to determine the cellular localization and regulation of this growth factor by the hormone gastrin. Analysis of PthlhLacZ/+ knock-in reporter mice localized Pthlh expression to parietal cells in the gastric corpus. Regulation by gastrin was demonstrated by increased Pthlh mRNA abundance after acute gastrin treatment in wild-type mice and reduced expression in gastrin-deficient mice. PTHLH transcripts were also observed in normal human stomach as well as in human gastric cancer cell lines. Gastrin treatment of AGS-E gastr...
Source: AJP: Gastrointestinal and Liver Physiology - June 8, 2017 Category: Gastroenterology Authors: Al Menhali, A., Keeley, T. M., Demitrack, E. S., Samuelson, L. C. Tags: RESEARCH ARTICLE Source Type: research

Transient receptor potential ion channel function in sensory transduction and cellular signaling cascades underlying visceral hypersensitivity
Visceral hypersensitivity is an important mechanism underlying increased abdominal pain perception in functional gastrointestinal disorders including functional dyspepsia, irritable bowel syndrome, and inflammatory bowel disease in remission. Although the exact pathophysiological mechanisms are poorly understood, recent studies described upregulation and altered functions of nociceptors and their signaling pathways in aberrant visceral nociception, in particular the transient receptor potential (TRP) channel family. A variety of TRP channels are present in the gastrointestinal tract (TRPV1, TRPV3, TRPV4, TRPA1, TRPM2, TRPM...
Source: AJP: Gastrointestinal and Liver Physiology - June 8, 2017 Category: Gastroenterology Authors: Balemans, D., Boeckxstaens, G. E., Talavera, K., Wouters, M. M. Tags: PERSPECTIVE Source Type: research

Intermediate filament proteins of digestive organs: physiology and pathophysiology
Intermediate filament proteins (IFs), such as cytoplasmic keratins in epithelial cells and vimentin in mesenchymal cells and the nuclear lamins, make up one of the three major cytoskeletal protein families. Whether in digestive organs or other tissues, IFs share several unique features including stress-inducible overexpression, abundance, cell-selective and differentiation state expression, and association with >80 human diseases when mutated. Whereas most IF mutations cause disease, mutations in simple epithelial keratins 8, 18, or 19 or in lamin A/C predispose to liver disease with or without other tissue manifestatio...
Source: AJP: Gastrointestinal and Liver Physiology - June 8, 2017 Category: Gastroenterology Authors: Omary, M. B. Tags: MINI-REVIEW Source Type: research

Old and new models for studying host-microbe interactions in health and disease: C. difficile as an example
There has been an explosion of interest in studying the indigenous microbiota, which plays an important role in human health and disease. Traditionally, the study of microbes in relationship to human health involved consideration of individual microbial species that caused classical infectious diseases. With the interest in the human microbiome, an appreciation of the influence that complex communities of microbes can have on their environment has developed. When considering either individual pathogenic microbes or a symbiotic microbial community, researchers have employed a variety of model systems with which they can stu...
Source: AJP: Gastrointestinal and Liver Physiology - June 8, 2017 Category: Gastroenterology Authors: Young, V. B. Tags: MINI-REVIEW Source Type: research

Barretts metaplasia develops from cellular reprograming of esophageal squamous epithelium due to gastroesophageal reflux
This study provides evidence that chronic exposure to the physiological components of gastric refluxate leads to repression of the discernable squamous transcriptional factors and activation of latent columnar transcriptional factors. This reflects the alteration in lineage commitment of the precursor-like biphenotypic, NES-B10T cells in response to A + B exposure as the possible origin of BM from the resident NES cells. NEW & NOTEWORTHY This study provides evidence of the origins of Barrett’s metaplasia from lineage transcommitment of resident esophageal cells after chronic exposure to gastroesophageal refluxate...
Source: AJP: Gastrointestinal and Liver Physiology - June 1, 2017 Category: Gastroenterology Authors: Minacapelli, C. D., Bajpai, M., Geng, X., Cheng, C. L., Chouthai, A. A., Souza, R., Spechler, S. J., Das, K. M. Tags: RESEARCH ARTICLE Source Type: research

Detection of human elastase isoforms by the ScheBo Pancreatic Elastase 1 Test
This study was undertaken to clarify which human pancreatic elastase isoforms are detected by the ScheBo Pancreatic Elastase 1 Stool Test and whether naturally occurring genetic variants influence the performance of this test. Using recombinantly expressed and purified human pancreatic proteinases, we found that the test specifically measured chymotrypsin-like elastases (CELA) 3A and 3B (CELA3A and CELA3B), while CELA2A was not detected. Inactive proelastases, active elastases, and autolyzed forms were detected with identical efficiency. CELA3B elicited approximately four times higher ELISA signal than CELA3A, and we ident...
Source: AJP: Gastrointestinal and Liver Physiology - June 1, 2017 Category: Gastroenterology Authors: Toth, A. Z., Szabo, A., Hegyi, E., Hegyi, P., Sahin-Toth, M. Tags: RESEARCH ARTICLE Source Type: research

Nutrient sensing by absorptive and secretory progenies of small intestinal stem cells
Nutrient sensing triggers responses by the gut-brain axis modulating hormone release, feeding behavior and metabolism that become dysregulated in metabolic syndrome and some cancers. Except for absorptive enterocytes and secretory enteroendocrine cells, the ability of many intestinal cell types to sense nutrients is still unknown; hence we hypothesized that progenitor stem cells (intestinal stem cells, ISC) possess nutrient sensing ability inherited by progenies during differentiation. We directed via modulators of Wnt and Notch signaling differentiation of precursor mouse intestinal crypts into specialized organoids each ...
Source: AJP: Gastrointestinal and Liver Physiology - June 1, 2017 Category: Gastroenterology Authors: Kishida, K., Pearce, S. C., Yu, S., Gao, N., Ferraris, R. P. Tags: RESEARCH ARTICLE Source Type: research

Glycans in the intestinal peptide transporter PEPT1 contribute to function and protect from proteolysis
This study highlights the role of N50-linked glycans in modulating the bidirectional transport activity of the murine peptide transporter PEPT1. Electrophysiological and tracer flux measurements in Xenopus oocytes have shown that removal of the N50 glycans increases the maximal peptide transport rate in the inward and outward directions. This effect could be largely reversed by replacement of N50 glycans with structurally dissimilar biotin derivatives. In addition, N-glycans were detected to stabilize PEPT1 against proteolytic cleavage. (Source: AJP: Gastrointestinal and Liver Physiology)
Source: AJP: Gastrointestinal and Liver Physiology - June 1, 2017 Category: Gastroenterology Authors: Stelzl, T., Geillinger-Kästle, K. E., Stolz, J., Daniel, H. Tags: RESEARCH ARTICLE Source Type: research

EAVK segment "c" sequence confers Ca2+-dependent changes to the kinetics of full-length human Ano1
Anoctamin1 (Ano1 and TMEM16A) is a calcium-activated chloride channel specifically expressed in the interstitial cells of Cajal (ICC) of the gastrointestinal tract muscularis propria. Ano1 is necessary for normal electrical slow waves and ICC proliferation. The full-length human Ano1 sequence includes an additional exon, exon "0," at the NH2 terminus. Ano1 with exon 0 [Ano1(0)] had a lower EC50 for intracellular calcium ([Ca2+]i) and faster chloride current (ICl) kinetics. The Ano1 alternative splice variant with segment "c" encoding exon 13 expresses on the first intracellular loop four additional amino acid residues, EAV...
Source: AJP: Gastrointestinal and Liver Physiology - June 1, 2017 Category: Gastroenterology Authors: Strege, P. R., Gibbons, S. J., Mazzone, A., Bernard, C. E., Beyder, A., Farrugia, G. Tags: RESEARCH ARTICLE Source Type: research

Changes in intestinal microbiota composition and metabolism coincide with increased intestinal permeability in young adults under prolonged physiological stress
This study used a systems biology approach and a multiple-stressor military training environment to determine the effects of physiological stress on intestinal microbiota composition and metabolic activity, as well as intestinal permeability (IP). Soldiers (n = 73) were provided three rations per day with or without protein- or carbohydrate-based supplements during a 4-day cross-country ski-march (STRESS). IP was measured before and during STRESS. Blood and stool samples were collected before and after STRESS to measure inflammation, stool microbiota, and stool and plasma global metabolite profiles. IP increased 62 ±...
Source: AJP: Gastrointestinal and Liver Physiology - June 1, 2017 Category: Gastroenterology Authors: Karl, J. P., Margolis, L. M., Madslien, E. H., Murphy, N. E., Castellani, J. W., Gundersen, Y., Hoke, A. V., Levangie, M. W., Kumar, R., Chakraborty, N., Gautam, A., Hammamieh, R., Martini, S., Montain, S. J., Pasiakos, S. M. Tags: RESEARCH ARTICLE Source Type: research

Ursodeoxycholic acid and lithocholic acid exert anti-inflammatory actions in the colon
Ward JB, Lajczak NK, Kelly OB, O’Dwyer AM, Giddam AK, Ní Gabhann J, Franco P, Tambuwala MM, Jefferies CA, Keely S, Roda A, Keely SJ. Ursodeoxycholic acid and lithocholic acid exert anti-inflammatory actions in the colon. Am J Physiol Gastrointest Liver Physiol 312: G550–G558, 2017. First published March 30, 2017; doi:10.1152/ajpgi.00256.2016.—Inflammatory bowel diseases (IBD) comprise a group of common and debilitating chronic intestinal disorders for which currently available therapies are often unsatisfactory. The naturally occurring secondary bile acid, ursodeoxycholic acid (UDCA), has well-esta...
Source: AJP: Gastrointestinal and Liver Physiology - June 1, 2017 Category: Gastroenterology Authors: Ward, J. B. J., Lajczak, N. K., Kelly, O. B., ODwyer, A. M., Giddam, A. K., Ni Gabhann, J., Franco, P., Tambuwala, M. M., Jefferies, C. A., Keely, S., Roda, A., Keely, S. J. Tags: RESEARCH ARTICLE Source Type: research