Determinants of postprandial plasma bile acid kinetics in human volunteers
Bile acids (BA) are signaling molecules with a wide range of biological effects, also identified among the most responsive plasma metabolites in the postprandial state. We here describe this response to different dietary challenges and report on key determinants linked to its interindividual variability. Healthy men and women (n = 72, 62 ± 8 yr, mean ± SE) were enrolled into a 12-wk weight loss intervention. All subjects underwent an oral glucose tolerance test and a mixed-meal tolerance test before and after the intervention. BA were quantified in plasma by liquid chromatography-tandem mass spectrometry comb...
Source: AJP: Gastrointestinal and Liver Physiology - October 1, 2017 Category: Gastroenterology Authors: Fiamoncini, J., Yiorkas, A. M., Gedrich, K., Rundle, M., Alsters, S. I., Roeselers, G., van den Broek, T. J., Clavel, T., Lagkouvardos, I., Wopereis, S., Frost, G., van Ommen, B., Blakemore, A. I., Daniel, H. Tags: RESEARCH ARTICLE Source Type: research

Dclk1-expressing tuft cells: critical modulators of the intestinal niche?
Dclk1-expressing tuft cells constitute a unique intestinal epithelial lineage that is distinct from enterocytes, Paneth cells, goblet cells, and enteroendocrine cells. Tuft cells express taste-related receptors and distinct transcription factors and interact closely with the enteric nervous system, suggesting a chemosensory cell lineage. In addition, recent work has shown that tuft cells interact closely with cells of the immune system, with a critical role in the cellular regulatory network governing responses to luminal parasites. Importantly, ablation of tuft cells severely impairs epithelial proliferation and tissue re...
Source: AJP: Gastrointestinal and Liver Physiology - October 1, 2017 Category: Gastroenterology Authors: Middelhoff, M., Westphalen, C. B., Hayakawa, Y., Yan, K. S., Gershon, M. D., Wang, T. C., Quante, M. Tags: REVIEW Source Type: research

RNA-seq implicates deregulation of the immune system in the pathogenesis of diverticulitis
Individuals with diverticula or outpouchings of the colonic mucosa and submucosa through the colonic wall have diverticulosis, which is usually asymptomatic. In 10-25% of individuals, the diverticula become inflamed, resulting in diverticulitis. Very little is known about the pathophysiology or gene regulatory pathways involved in the development of diverticulitis. To identify these pathways, we deep sequenced RNAs isolated from full-thickness sections of sigmoid colon from diverticulitis patients and control individuals. Specifically for diverticulitis cases, we analyzed tissue adjacent to areas affected by chronic diseas...
Source: AJP: Gastrointestinal and Liver Physiology - September 1, 2017 Category: Gastroenterology Authors: Schieffer, K. M., Choi, C. S., Emrich, S., Harris, L., Deiling, S., Karamchandani, D. M., Salzberg, A., Kawasawa, Y. I., Yochum, G. S., Koltun, W. A. Tags: RAPID REPORT Source Type: research

High-resolution mapping of gastric slow-wave recovery profiles: biophysical model, methodology, and demonstration of applications
Slow waves play a central role in coordinating gastric motor activity. High-resolution mapping of extracellular potentials from the stomach provides spatiotemporal detail on normal and dysrhythmic slow-wave patterns. All mapping studies to date have focused exclusively on tissue activation; however, the recovery phase contains vital information on repolarization heterogeneity, the excitable gap, and refractory tail interactions but has not been investigated. Here, we report a method to identify the recovery phase in slow-wave mapping data. We first developed a mathematical model of unipolar extracellular potentials that re...
Source: AJP: Gastrointestinal and Liver Physiology - September 1, 2017 Category: Gastroenterology Authors: Paskaranandavadivel, N., Cheng, L. K., Du, P., Rogers, J. M., OGrady, G. Tags: INNOVATIVE METHODOLOGY Source Type: research

CDX2 upregulates SLC26A3 gene expression in intestinal epithelial cells
SLC26A3 [downregulated in adenoma (DRA)] plays a key role in mammalian intestinal NaCl absorption, in that it mediates apical membrane Cl–/HCO3– exchange. DRA function and expression are significantly decreased in diarrhea associated with inflammatory bowel disease. DRA is also considered to be a marker of cellular differentiation and is predominantly expressed in differentiated epithelial cells. Caudal-type homeobox protein-2 (CDX2) is known to regulate genes involved in intestinal epithelial differentiation and proliferation. Reduced expression of both DRA and CDX2 in intestinal inflammation prompted us to st...
Source: AJP: Gastrointestinal and Liver Physiology - September 1, 2017 Category: Gastroenterology Authors: Chatterjee, I., Kumar, A., Castilla-Madrigal, R. M., Pellon-Cardenas, O., Gill, R. K., Alrefai, W. A., Borthakur, A., Verzi, M., Dudeja, P. K. Tags: RESEARCH ARTICLE Source Type: research

Activated Notch signaling cascade is correlated with stem cell differentiation toward absorptive progenitors after massive small bowel resection in a rat
In conclusion, 2 wk after bowel resection in rats, stimulated Notch signaling directs the crypt cell population toward absorptive progenitors. NEW & NOTEWORTHY This study provides novel insight into the mechanisms of cell proliferation following massive small bowel resection. We show that 2 wk after bowel resection in rats, enhanced stem cell activity was associated with stimulated Notch signaling pathway. We demonstrate that activated Notch signaling cascade directs the crypt cell population toward absorptive progenitors. (Source: AJP: Gastrointestinal and Liver Physiology)
Source: AJP: Gastrointestinal and Liver Physiology - September 1, 2017 Category: Gastroenterology Authors: Sukhotnik, I., Coran, A. G., Pollak, Y., Kuhnreich, E., Berkowitz, D., Saxena, A. K. Tags: RESEARCH ARTICLE Source Type: research

Oatmeal particle size alters glycemic index but not as a function of gastric emptying rate
The aim of this study was to determine the extent to which oat particle size in a porridge could alter glucose absorption, gastric emptying, gastrointestinal hormone response, and subjective feelings of appetite and satiety. Porridge was prepared from either oat flakes or oat flour with the same protein, fat, carbohydrate, and mass. These were fed to eight volunteers on separate days in a crossover study, and subjective appetite ratings, gastric contents, and plasma glucose, insulin, and gastrointestinal hormones were determined over a period of 3 h. The flake porridge gave a lower glucose response than the flour porridge,...
Source: AJP: Gastrointestinal and Liver Physiology - September 1, 2017 Category: Gastroenterology Authors: Mackie, A. R., Bajka, B. H., Rigby, N. M., Wilde, P. J., Alves-Pereira, F., Mosleth, E. F., Rieder, A., Kirkhus, B., Salt, L. J. Tags: RESEARCH ARTICLE Source Type: research

Disease activity in eosinophilic esophagitis is associated with impaired esophageal barrier integrity
In eosinophilic esophagitis (EoE), the esophageal barrier integrity is impaired. Integrity can be assessed with different techniques. To assess the correlations between esophageal eosinophilia and various measures of mucosal integrity and to evaluate whether endoscopic impedance measurements can predict disease activity, endoscopies and mucosal integrity measurements were performed in adult EoE patients with active disease (≥15 eosinophils/high-power field) at baseline (n = 32) and after fluticasone (n = 15) and elemental dietary treatment (n = 14) and in controls (n = 19). Mucosal integrity was evaluated during endosco...
Source: AJP: Gastrointestinal and Liver Physiology - September 1, 2017 Category: Gastroenterology Authors: Warners, M. J., van Rhijn, B. D., Verheij, J., Smout, A. J. P. M., Bredenoord, A. J. Tags: RESEARCH ARTICLE Source Type: research

Characterization and mechanisms of the supragastric belch in the cat
A response in which a belch occurs without gastric involvement, i.e., the supragastric belch (SGB), has been characterized in humans. The aims of this study were to determine whether animals have an SGB and, if so, to determine its mechanisms. Studies were conducted in decerebrate cats (n = 30) with electromyographic electrodes on hyoid, pharyngeal, esophageal, and diaphragm muscles. The effects of distending different regions of the esophagus in different manners using a balloon were quantified to determine the most appropriate stimulus for activating the cat SGB. The effects of esophageal perfusion of lidocaine (n = 3), ...
Source: AJP: Gastrointestinal and Liver Physiology - September 1, 2017 Category: Gastroenterology Authors: Lang, I. M., Medda, B. K., Shaker, R. Tags: RESEARCH ARTICLE Source Type: research

Functional morphology of the lower esophageal sphincter and crural diaphragm determined by three-dimensional high-resolution esophago-gastric junction pressure profile and CT imaging
The smooth muscles of the lower esophageal sphincter (LES) and skeletal muscles of the crural diaphragm (CD) provide a closure/antireflux barrier mechanism at the esophago-gastric junction (EGJ). A number of questions in regard to the pressure profile of the LES and CD remain unclear, e.g., 1) Why is the LES pressure profile circumferentially asymmetric, 2) Is the crural diaphragm (CD) contraction also circumferentially asymmetric, and 3) Where is the LES and CD pressure profile located in the anatomy of the esophagus and stomach? The three-dimensional (3-D) high-resolution esophageal manometry (HRM) catheter can record a ...
Source: AJP: Gastrointestinal and Liver Physiology - September 1, 2017 Category: Gastroenterology Authors: Mittal, R. K., Zifan, A., Kumar, D., Ledgerwood-Lee, M., Ruppert, E., Ghahremani, G. Tags: RESEARCH ARTICLE Source Type: research

Dysfunctional neutrophil effector organelle mobilization and microbicidal protein release in alcohol-related cirrhosis
Patients with alcohol-related cirrhosis (ALD) are prone to infection. Circulating neutrophils in ALD are dysfunctional and predict development of sepsis, organ dysfunction, and survival. Neutrophil granules are important effector organelles containing a toxic array of microbicidal proteins, whose controlled release is required to kill microorganisms while minimizing inflammation and damage to host tissue. We investigated the role of these granular responses in contributing to immune disarray in ALD. Neutrophil granular content and mobilization were measured by flow cytometric quantitation of cell-surface/intracellular mark...
Source: AJP: Gastrointestinal and Liver Physiology - September 1, 2017 Category: Gastroenterology Authors: Tranah, T. H., Vijay, G. K. M., Ryan, J. M., Abeles, R. D., Middleton, P. K., Shawcross, D. L. Tags: RESEARCH ARTICLE Source Type: research

Anti-inflammatory effects and mechanisms of vagal nerve stimulation combined with electroacupuncture in a rodent model of TNBS-induced colitis
In conclusion, chronic VNS improves inflammation in TNBS-treated rats by inhibiting proinflammatory cytokines via the autonomic mechanism. Addition of noninvasive EA to VNS may enhance the anti-inflammatory effect of VNS. NEW & NOTEWORTHY This is the first study to address and compare the effects of vagal nerve stimulation (VNS), electrical acupuncture (EA) and VNS + EA on TNBS (2,4,6-trinitrobenzenesulfonic acid)-induced colitis in rats. The proposed chronic VNS + EA, VNS, and EA were shown to decrease DAI and ameliorate macroscopic and microscopic damages in rats with TNBS-induced colitis via the autonomic pathway. T...
Source: AJP: Gastrointestinal and Liver Physiology - September 1, 2017 Category: Gastroenterology Authors: Jin, H., Guo, J., Liu, J., Lyu, B., Foreman, R. D., Yin, J., Shi, Z., Chen, J. D. Z. Tags: RESEARCH ARTICLE Source Type: research

Ductular and proliferative response of esophageal submucosal glands in a porcine model of esophageal injury and repair
Esophageal injury is a risk factor for diseases such as Barrett’s esophagus (BE) and esophageal adenocarcinoma. To improve understanding of signaling pathways associated with both normal and abnormal repair, animal models are needed. Traditional rodent models of esophageal repair are limited by the absence of esophageal submucosal glands (ESMGs), which are present in the human esophagus. Previously, we identified acinar ductal metaplasia in human ESMGs in association with both esophageal injury and cancer. In addition, the SOX9 transcription factor has been associated with generation of columnar epithelium and the pa...
Source: AJP: Gastrointestinal and Liver Physiology - September 1, 2017 Category: Gastroenterology Authors: Krüger, L., Gonzalez, L. M., Pridgen, T. A., McCall, S. J., von Furstenberg, R. J., Harnden, I., Carnighan, G. E., Cox, A. M., Blikslager, A. T., Garman, K. S. Tags: RESEARCH ARTICLE Source Type: research

Loss of the anion exchanger DRA (Slc26a3), or PAT1 (Slc26a6), alters sulfate transport by the distal ileum and overall sulfate homeostasis
The ileum is considered the primary site of inorganic sulfate (SO42–) absorption. In the present study, we explored the contributions of the apical chloride/bicarbonate (Cl–/HCO3–) exchangers downregulated in adenoma (DRA; Slc26a3), and putative anion transporter 1 (PAT1; Slc26a6), to the underlying transport mechanism. Transepithelial 35SO42– and 36Cl– fluxes were determined across isolated, short-circuited segments of the distal ileum from wild-type (WT), DRA-knockout (KO), and PAT1-KO mice, together with measurements of urine and plasma sulfate. The WT distal ileum supported net sulfate abs...
Source: AJP: Gastrointestinal and Liver Physiology - September 1, 2017 Category: Gastroenterology Authors: Whittamore, J. M., Hatch, M. Tags: RESEARCH ARTICLE Source Type: research

The liver in regulation of iron homeostasis
The liver is one of the largest and most functionally diverse organs in the human body. In addition to roles in detoxification of xenobiotics, digestion, synthesis of important plasma proteins, gluconeogenesis, lipid metabolism, and storage, the liver also plays a significant role in iron homeostasis. Apart from being the storage site for excess body iron, it also plays a vital role in regulating the amount of iron released into the blood by enterocytes and macrophages. Since iron is essential for many important physiological and molecular processes, it increases the importance of liver in the proper functioning of the bod...
Source: AJP: Gastrointestinal and Liver Physiology - September 1, 2017 Category: Gastroenterology Authors: Rishi, G., Subramaniam, V. N. Tags: REVIEW Source Type: research