5,210 results match your criteria American Journal of Physiology - Gastrointestinal and Liver Physiology [Journal]


Defense mechanisms to increasing back pressure for hepatic oxygen transport and venous return in porcine fecal peritonitis.

Am J Physiol Gastrointest Liver Physiol 2020 Jul 13. Epub 2020 Jul 13.

Department of Intensive Care Medicine, Bern University Hospital, University of Bern, Switzerland.

High central venous pressure (CVP) acutely decreases venous return. How this affects hepatic oxygen transport in sepsis remains unclear. The aim of this study was to evaluate the effects of repeated increases of CVP via standard nursing procedures (NPs) on hepato-splanchnic and renal oxygen transport in a prolonged porcine sepsis model. Read More

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http://dx.doi.org/10.1152/ajpgi.00216.2020DOI Listing

TNF-α, IL-17 AND IL-22 PRODUCTION IN THE RECTAL MUCOSA OF NON-CELIAC WHEAT SENSITIVITY PATIENTS: ROLE OF ADAPTIVE IMMUNITY.

Am J Physiol Gastrointest Liver Physiol 2020 Jul 13. Epub 2020 Jul 13.

Internal Medicine, Sciacca Hospital, and University of Palermo, Palermo, Italy., Italy.

In recent years, a new gluten- or wheat-related disease has emerged, a condition labelled "non-celiac gluten sensitivity" (NCGS) or "non-celiac wheat sensitivity" (NCWS). NCWS pathogenesis is still uncertain and attributed to very different mechanisms. We aimed to study the different T lymphocyte subsets in the rectal mucosa of NCWS patients, to demonstrate the possible contribution of adaptative immune response. Read More

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http://dx.doi.org/10.1152/ajpgi.00104.2020DOI Listing

Talk about micromanaging! Role of microRNAs in intestinal barrier function.

Am J Physiol Gastrointest Liver Physiol 2020 Jul 13. Epub 2020 Jul 13.

Medicine, Pennsylvania State University, United States.

Defective intestinal tight junction (TJ) barrier has been implicated in the pathogenesis of inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), and other inflammatory conditions of the gut. The role of microRNAs (miRNA's or miR's) has also been demonstrated in the last two decades in the pathogenesis of IBD and in the regulation of intestinal TJ barrier function. MiRNAs are non-coding regulators of gene expression at the post-transcription level that have essential role in targeting transcripts encoding proteins of intestinal TJ and their regulators. Read More

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http://dx.doi.org/10.1152/ajpgi.00214.2020DOI Listing

Gastrointestinal Organoids: A Next Generation Tool for Modeling Human Development.

Am J Physiol Gastrointest Liver Physiol 2020 Jul 13. Epub 2020 Jul 13.

Colorectal Center for Children, Cincinnati Children's Hospital, United States.

Gastrointestinal organoids are an exciting new tool for modeling human development, physiology, and disease in human tissue. Derived from pluripotent stem cells (PSCs), gastrointestinal organoids consist of epithelial and mesenchymal cells organized in an intricate, three-dimensional structure that recapitulates the physiology and microscopic anatomy of the human GI tract. In vitro derivation of gastrointestinal organoids from Definitive Endoderm has permitted an exploration of the complex signaling pathways required for the initial maturation of each individual gastrointestinal organ. Read More

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http://dx.doi.org/10.1152/ajpgi.00199.2020DOI Listing

The mechanism and treatment of gastrointestinal symptoms in patients with COVID-19.

Am J Physiol Gastrointest Liver Physiol 2020 Jul 8. Epub 2020 Jul 8.

National Clinical Research Center for Child Health, Zhejiang University School of Children's Hospital, China.

In addition to the typical respiratory response, new coronavirus pneumonia (COVID-19) is also associated with very common gastrointestinal symptoms. Cases with gastrointestinal symptoms are more likely to be complicated by liver injury and acute respiratory distress syndrome (ARDS), and diarrhea can also lead to electrolyte disturbances, causing nausea and vomiting, headache, fatigue, etc. If not treated in time, coma and circulatory failure may ensue. Read More

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http://dx.doi.org/10.1152/ajpgi.00148.2020DOI Listing

ASSOCIATIONS OF GASTRIC VOLUMES, INGESTIVE BEHAVIOR, CALORIE AND VOLUME INTAKE, AND FULLNESS IN OBESITY.

Am J Physiol Gastrointest Liver Physiol 2020 Jul 6. Epub 2020 Jul 6.

Gastroenterology and Hepatology, Mayo Clinic, United States.

Introduction: Whereas gastric emptying significantly predicts calorie intake, the association between gastric capacity and satiation and satiety is unclear.

Aim: To study associations between gastric volumes and ingestive behaviors with satiation and satiety in obesity.

Methods: Sixty-two healthy adult obese patients (57 female) with no eating disorders underwent measurements of satiety by kcal ingestion at buffet meal, satiation by volume to comfortable fullness (VTF) and maximum tolerated volume (MTV) while drinking Ensure® (30 mL/min), and fasting and postprandial gastric volumes by validated single photon emission computed tomography. Read More

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http://dx.doi.org/10.1152/ajpgi.00140.2020DOI Listing

The role of glucuronidated 25-hydroxyvitamin D on colon gene expression in mice.

Am J Physiol Gastrointest Liver Physiol 2020 Jul 6. Epub 2020 Jul 6.

Biomedical Sciences, Iowa State University, United States.

25-Hydroxyvitamin D-3β-glucuronic acid (25OHD-Gluc) is produced in the liver and is a constituent of human blood and bile. Bacterial glucuronidases (GUS) in mammalian digestive microbiota cleave glucuronide conjugates, such as 25OHD-Gluc, and release the free aglycone (i.e. Read More

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http://dx.doi.org/10.1152/ajpgi.00355.2019DOI Listing

Epigenetic regulation of intestinal stem cell differentiation.

Am J Physiol Gastrointest Liver Physiol 2020 Jul 6. Epub 2020 Jul 6.

Medical Oncology, Dana-Farber Cancer Institute, United States.

To fulfill the lifelong need to supply diverse epithelial cells, intestinal stem cells (ISCs) rely on executing accurate transcriptional programs. This review addresses the mechanisms that control those programs. Genes that define cell behaviors and identities are regulated principally through thousands of dispersed enhancers, each individually <1 kb long and positioned from a few to hundreds of kilobases away from transcription start sites, upstream or downstream from coding genes or within introns. Read More

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http://dx.doi.org/10.1152/ajpgi.00084.2020DOI Listing

Grading TESI: Crypt and villus formation in tissue-engineered small intestine alters with stem/progenitor cell source.

Am J Physiol Gastrointest Liver Physiol 2020 Jun 29. Epub 2020 Jun 29.

Surgery, Childrens Hospital Los Angeles/The Saban Research Institute, United States.

The small intestine has a remarkable ability to enhance its absorptive and digestive surface area through the formation of villi, a process known as villification. We sought to learn if developing mouse and human tissue-engineered small intestine (TESI) followed known developmental biology routes to villification such as Shh/Ihh and BMP4/FoxF1 signaling in order to identify targets to enhance the development of TESI. After generating TESI from prenatal and postnatal stem cell sources, we evaluated the effect of cell source derivation on villification with a grading scheme to approximate developmental stage. Read More

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http://dx.doi.org/10.1152/ajpgi.00387.2019DOI Listing

Broad spectrum antibiotics alter the microbiome, increase intestinal fxr, and decrease hepatic steatosis in zebrafish short bowel syndrome.

Am J Physiol Gastrointest Liver Physiol 2020 Jun 29. Epub 2020 Jun 29.

Surgery, Childrens Hospital Los Angeles/The Saban Research Institute, United States.

Short bowel syndrome (SBS) is associated with changes in the intestinal microbiome and marked local and systemic inflammation. There is also a late complication of SBS, intestinal failure associated liver disease (IFALD) in which hepatic steatosis progresses to cirrhosis. Most patients with SBS arrive at massive intestinal resection after a contaminating intraabdominal catastrophe and have a history of exposure to broad spectrum antibiotics. Read More

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http://dx.doi.org/10.1152/ajpgi.00119.2020DOI Listing

Early normalization of reduced urea synthesis capacity after direct-acting antiviral therapy in hepatitis C cirrhosis.

Am J Physiol Gastrointest Liver Physiol 2020 Jun 29. Epub 2020 Jun 29.

Department of Medicine V, Aarhus University Hospital, Albania.

Background And Aims: Effects of direct-acting antiviral (DAA)-treatment of chronic hepatitis C (CHC) cirrhosis on metabolic liver function are unknown but important for prognosis. Ureagenesis is an essential metabolic liver function involved in whole-body nitrogen homeostasis. We aimed to investigate the ureagenesis capacity before and immediatelyafter DAA-therapy and relate the findings to hepatic inflammation and structural changes. Read More

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http://dx.doi.org/10.1152/ajpgi.00128.2020DOI Listing

Obeticholic acid improves fetal bile acid profile in a mouse model of gestational hypercholanemia.

Am J Physiol Gastrointest Liver Physiol 2020 Jun 29. Epub 2020 Jun 29.

King's College London.

Intrahepatic cholestasis of pregnancy (ICP) is characterized by elevated maternal circulating bile acid levels and associated dyslipidemia. ICP leads to accumulation of bile acids in the fetal compartment and the elevated bile acid concentrations are associated with an increased risk of adverse fetal outcomes. The farnesoid X receptor agonist, obeticholic acid (OCA) is efficient in the treatment of cholestatic conditions such as primary biliary cholangitis. Read More

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http://dx.doi.org/10.1152/ajpgi.00126.2020DOI Listing

Ridinilazole, a narrow spectrum antibiotic for treatment of Clostridioides difficile infection, enhances preservation of microbiota-dependent bile acids.

Am J Physiol Gastrointest Liver Physiol 2020 Jun 29. Epub 2020 Jun 29.

Tufts Medical Center.

Antibiotic treatment is a standard therapy for Clostridioides difficile infection, but dysbiosis of the gut microbiota due to antibiotic exposure is also a major risk factor for the disease. Following an initial episode of C. difficile infection, a relentless cycle of recurrence can occur, where persistent treatment-related dysbiosis predisposes the patient to subsequent relapse. Read More

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http://dx.doi.org/10.1152/ajpgi.00046.2020DOI Listing

Mitochondrial oxidative injury: A key player in nonalcoholic fatty liver disease.

Am J Physiol Gastrointest Liver Physiol 2020 Jun 29. Epub 2020 Jun 29.

Harvard Medical School.

Nonalcoholic fatty liver disease (NAFLD) has become the most prevalent liver disease worldwide. NAFLD is tightly linked to the metabolic syndrome, insulin resistance and oxidative stress. Globally, its inflammatory form, nonalcoholic steatohepatitis (NASH), has become the main cause of liver related morbidity and mortality, mainly due to liver cirrhosis and primary liver cancer. Read More

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http://dx.doi.org/10.1152/ajpgi.00121.2020DOI Listing

The reabsorption of bile acids regulated by FXR-OATP1A2 is the main factor for the formation of cholesterol gallstone.

Am J Physiol Gastrointest Liver Physiol 2020 Jun 29. Epub 2020 Jun 29.

Department of General Surgery, Shanghai General Hospita, Shanghai Jiao Tong University School of Medicine, Shanghai, China, China.

The purpose of this study was to demonstrate the aberrant metabolism of bile acids in patients with cholesterol gallstone and explore for its underlying mechanisms.The composition of bile acids collected from the patients with cholelithiasis and the control individuals was analyzed by LC-MS. The expression of genes regulating the metabolism of bile acids were quantitatively determined by real-time PCR or Western blotting. Read More

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http://dx.doi.org/10.1152/ajpgi.00385.2019DOI Listing
June 2020
3.798 Impact Factor

Glucocorticoids and Serum and Glucocorticoid-inducible kinase 1 are potent regulators of CFTR in the native intestine: implications for stress-induced diarrhea.

Am J Physiol Gastrointest Liver Physiol 2020 Jun 22. Epub 2020 Jun 22.

Pediatrics, Yale University School of Medicine, United States.

Non-genomic Glucocorticoid (GC) and Serum and Glucocorticoid-inducible kinase 1 (SGK1) signaling regulate ion transport, but CFTR has not been investigated in the intestine. We examined GC, SGK1 and phosphoinositide 3-kinase (PI3K) kinase signaling of CFTR ion transport in native intestine and the role of GCs on mRNA, protein, surface expression, and cyclic guanosine monophosphate (cGMP)-elicited diarrhea. Rats were treated with dexamethasone (DEXA 2mg/kg, IP) or DMSO for 1, 4 and 24 h. Read More

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http://dx.doi.org/10.1152/ajpgi.00076.2020DOI Listing
June 2020
3.798 Impact Factor

Parallel intermediate conductance K (IK) and Cl (CLC2) channel activity mediates electroneutral K exit across basolateral membranes in rat distal colon.

Am J Physiol Gastrointest Liver Physiol 2020 Jun 22. Epub 2020 Jun 22.

West Virginia University School of Medicine, Morgantown, West Virginia; Medicine, Digestive Diseases Section, West Virginia University School of Medicine, Morgantown, West Virginia.

Transepithelial K absorption requires apical K uptake and basolateral K exit. In colon, apical H,K-ATPase mediates cellular K uptake, and it has been suggested that electroneutral basolateral K exit reflects K-Cl cotransporter-1 (KCC1) operating in parallel with K and Cl channels. Present study was designed to identify basolateral transporter(s) responsible for K exit in rat distal colon. Read More

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http://dx.doi.org/10.1152/ajpgi.00011.2020DOI Listing
June 2020
3.798 Impact Factor

Net release and uptake of xenometabolites across intestinal, hepatic, muscle, and renal tissue beds in healthy conscious pigs.

Am J Physiol Gastrointest Liver Physiol 2020 Jun 15. Epub 2020 Jun 15.

Department of Pediatrics, Arkansas Children's Nutrition Center, United States.

Xenometabolites from microbial and plant sources are thought to confer beneficial, as well as deleterious, effects on host physiology. Studies determining absorption and tissue uptake of xenometabolites are limited. We utilized a conscious catheterized pig model to evaluate inter-organ flux of annotated known and suspected xenometabolites, derivatives, and bile acids. Read More

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http://dx.doi.org/10.1152/ajpgi.00153.2020DOI Listing

Coordinate expression loss of GKN1 and GKN2 in gastric cancer via impairment of a glucocorticoid-responsive enhancer.

Am J Physiol Gastrointest Liver Physiol 2020 Jun 15. Epub 2020 Jun 15.

Murdoch Childrens Research Institute, Australia.

Gastrokines (GKNs) are anti-inflammatory proteins secreted by gastric epithelial (surface mucous and pit) cells, with their aberrant loss of expression causally linked to premalignant inflammation and gastric cancer (GC). Transcriptional mechanisms accounting for GKN expression loss have not been elucidated. Using human clinical cohorts, mouse transgenics, bioinformatics and transfection/reporter assays, we report a novel mechanism of GKN gene transcriptional regulation and its impairment in GC. Read More

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http://dx.doi.org/10.1152/ajpgi.00019.2020DOI Listing

Hyaluronic acid promotes Lgr5 stem cell proliferation and crypt fission through TLR4 and PGE transactivation of EGFR.

Am J Physiol Gastrointest Liver Physiol 2020 Jul 15;319(1):G63-G73. Epub 2020 Jun 15.

Division of Gastroenterology, Washington University School of Medicine, St. Louis, Missouri.

Hyaluronic acid (HA), a glycosaminoglycan in the extracellular matrix, binds to CD44 and Toll-like receptor 4 (TLR4). We previously demonstrated that both CD44 and TLR4, but predominately TLR4, mediated HA stimulation of Lgr5 stem cell proliferation, crypt fission, and intestinal growth in postnatal mice. Here we address the questions of which cell type expresses the relevant TLR4 in driving intestinal growth and what are the downstream events from TLR4 activation. Read More

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http://dx.doi.org/10.1152/ajpgi.00242.2019DOI Listing

Switching of cargo sorting from the constitutive to regulated secretory pathway by the addition of cystatin D sequence in salivary acinar cells.

Am J Physiol Gastrointest Liver Physiol 2020 Jul 15;319(1):G74-G86. Epub 2020 Jun 15.

Department of Physiology, Nihon University School of Dentistry at Matsudo, Matsudo, Chiba, Japan.

The mechanism for segregation of cargo proteins into the regulated and constitutive secretory pathways in exocrine cells remains to be elucidated. We examined the transport of HaloTag proteins fused with full-length cystatin D (fCst5-Halo) or only its signal peptide (ssCst5-Halo) in parotid acinar cells. Although both fusion proteins were observed to be colocalized with amylase in the secretory granules, the coefficients for overlapping and correlation of fCst5-Halo with amylase were higher than those of ssCst5-Halo. Read More

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http://dx.doi.org/10.1152/ajpgi.00103.2020DOI Listing

Hyperthermia-induced changes in liver physiology and metabolism: a rationale for hyperthermic machine perfusion.

Am J Physiol Gastrointest Liver Physiol 2020 Jul 8;319(1):G43-G50. Epub 2020 Jun 8.

Department of Surgery, Section of Hepatobiliary Surgery and Liver Transplantation, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

Liver transplantation is the standard treatment for end-stage liver disease. However, due to the ongoing disparity between supply and demand for optimal donor organs, there is increasing usage of extended criteria donor organs, including steatotic liver grafts. To mitigate the increased risks associated with extended criteria donor livers, ex situ oxygenated machine perfusion (MP) has received increasing attention in recent years as an emerging platform for dynamic preservation, reconditioning, and viability assessment to increase organ utilization. Read More

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http://dx.doi.org/10.1152/ajpgi.00101.2020DOI Listing

Xenometabolite signatures in the UC Davis Type 2 Diabetes Mellitus Rat model revealed using a metabolomics platform enriched with microbe-derived metabolites.

Am J Physiol Gastrointest Liver Physiol 2020 Jun 8. Epub 2020 Jun 8.

Department of Pediatrics, Arkansas Children's Nutrition Center, United States.

The gut microbiome has the potential to create or modify xenometabolites (i.e., non-host derived metabolites) through de novo synthesis or modification of exogenous and endogenous compounds. Read More

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http://dx.doi.org/10.1152/ajpgi.00105.2020DOI Listing

Transcriptomic identification of TMIGD1 and its relationship with the ileal epithelial cell differentiation in Crohn's disease.

Am J Physiol Gastrointest Liver Physiol 2020 Jun 8. Epub 2020 Jun 8.

Gastroenterology, IGTP/CIBER, Spain.

Background: Crohn's disease (CD) is a complex and multifactorial illness. There are still considerable gaps in our knowledge regarding its pathophysiology. A transcriptomic approach could shed some light on little-known biological alterations of the disease. Read More

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http://dx.doi.org/10.1152/ajpgi.00027.2020DOI Listing

Inhibition of LXR signaling by SULT2B1b promotes liver regeneration after partial hepatectomy in mouse models of nonalcoholic fatty liver disease.

Am J Physiol Gastrointest Liver Physiol 2020 Jul 1;319(1):G87-G96. Epub 2020 Jun 1.

Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, China.

Hydroxysteroid sulfotransferase 2B1b (SULT2B1b) plays a critical role in hepatic energy homeostasis. Liver X receptors (LXRs) are implicated in multiple physiological functions, including the inhibition of hepatocyte proliferation and regulation of fatty acid and cholesterol metabolism. We have previously reported that SULT2B1b promotes hepatocyte proliferation by inactivating LXR signaling in vivo and in vitro, leading to our hypothesis that SULT2B1b promotes fatty liver regeneration. Read More

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http://dx.doi.org/10.1152/ajpgi.00380.2019DOI Listing

Acetylcholine exerts inhibitory and excitatory actions on mouse ileal pacemaker activity: role of muscarinic versus nicotinic receptors.

Am J Physiol Gastrointest Liver Physiol 2020 Jul 1;319(1):G97-G107. Epub 2020 Jun 1.

School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong Special Administrative Region, People's Republic of China.

The effect of acetylcholine (ACh) on pacemaking and spontaneous contractions in the gastrointestinal tract is not well characterized. The current study aims to profile the effect of several muscarinic and nicotinic receptor agonists and antagonists on pacemaker potentials in the ICR mouse ileum. Pacemaker potentials of whole thickness mouse ileal segments were recorded extracellularly using a 60-channel microelectrode array (MEA) platform. Read More

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http://dx.doi.org/10.1152/ajpgi.00003.2020DOI Listing

Alterations in pancreatic islet cell function in response to small bowel resection.

Am J Physiol Gastrointest Liver Physiol 2020 Jul 28;319(1):G36-G42. Epub 2020 May 28.

Division of Pediatric Surgery, Department of Surgery, St. Louis Children's Hospital, Washington University School of Medicine, St. Louis, Missouri.

After 50% proximal small bowel resection (SBR) in mice, we have demonstrated hepatic steatosis, impaired glucose metabolism without insulin resistance, and increased pancreatic islet area. We sought to determine the consequences of SBR on pancreatic β-cell morphology, proliferation, and expression of a key regulatory hormone, glucagon-like peptide-1 (GLP-1). C57BL/6 mice underwent 50% SBR or sham operation. Read More

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http://dx.doi.org/10.1152/ajpgi.00282.2019DOI Listing

Lipid droplets disrupt mechanosensing in human hepatocytes.

Am J Physiol Gastrointest Liver Physiol 2020 Jul 28;319(1):G11-G22. Epub 2020 May 28.

Departments of Medicine and Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania.

Hepatocellular carcinoma (HCC) is the fourth-leading cause of cancer death in the world. Although most cases occur in stiff, cirrhotic livers, and stiffness is a significant risk factor, HCC can also arise in noncirrhotic livers in the setting of nonalcoholic fatty liver disease (NAFLD). We hypothesized that lipid droplets in NAFLD might apply mechanical forces to the nucleus, functioning as mechanical stressors akin to stiffness. Read More

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http://dx.doi.org/10.1152/ajpgi.00098.2020DOI Listing

microRNA-382 suppresses the progression of pancreatic cancer through the PI3K/Akt signaling pathway by inhibition of Anxa3.

Am J Physiol Gastrointest Liver Physiol 2020 May 28. Epub 2020 May 28.

Department of Hematology and Oncology, The Second Hospital of Jilin University, China.

Pancreatic cancer (PC) is a lethal cancer in the digestive system. microRNAs (miRNAs) have been demonstrated to participate in PC progression. In this context, we thus aimed to explore the mechanism of miR-382 in epithelial mesenchymal transition (EMT) and lymph node metastasis in PC in relation to Anxa3 and the PI3K/Akt signaling pathway. Read More

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http://dx.doi.org/10.1152/ajpgi.00322.2019DOI Listing

CORRIGENDUM.

Authors:

Am J Physiol Gastrointest Liver Physiol 2020 Jun;318(6):G1054

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http://dx.doi.org/10.1152/ajpgi.zh3-7794corr.2020DOI Listing

Microbial metabolite indole-3-propionic acid supplementation does not protect mice from the cardiometabolic consequences of a Western diet.

Am J Physiol Gastrointest Liver Physiol 2020 Jul 18;319(1):G51-G62. Epub 2020 May 18.

Department of Food Science and Human Nutrition, Colorado State University, Fort Collins, Colorado.

Emerging evidence suggests that intestinal microbes regulate host physiology and cardiometabolic health, although the mechanism(s) by which they do so is unclear. Indoles are a group of compounds produced from bacterial metabolism of the amino acid tryptophan. In light of recent data suggesting broad physiological effects of indoles on host physiology, we examined whether indole-3-propionic acid (IPA) would protect mice from the cardiometabolic consequences of a Western diet. Read More

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http://dx.doi.org/10.1152/ajpgi.00375.2019DOI Listing

Cellular maps of gastrointestinal organs: getting the most from tissue clearing.

Am J Physiol Gastrointest Liver Physiol 2020 Jul 18;319(1):G1-G10. Epub 2020 May 18.

Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Saban Research Institute Children's Hospital Los Angeles, Los Angeles, California.

The development of modern methods to induce optical transparency ("clearing") in biological tissues has enabled the three-dimensional (3D) reconstruction of intact organs at cellular resolution. New capabilities in visualization of rare cellular events, long-range interactions, and irregular structures will facilitate novel studies in the alimentary tract and gastrointestinal systems. The tubular geometry of the alimentary tract facilitates large-scale cellular reconstruction of cleared tissue without specialized microscopy setups. Read More

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http://dx.doi.org/10.1152/ajpgi.00075.2020DOI Listing

Glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide stimulate release of substance P from TRPV1- and TRPA1-expressing sensory nerves.

Am J Physiol Gastrointest Liver Physiol 2020 Jul 18;319(1):G23-G35. Epub 2020 May 18.

Department of Nutritional Sciences and Toxicology, Graduate Program in Metabolic Biology, University of California, Berkeley, California.

Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are released from enteroendocrine cells (EECs) in response to nutrient ingestion and lower blood glucose levels by stimulation of insulin secretion and thus are defined as incretins. GLP-1 receptor (GLP-1R) expression has been identified on enteric neurons that include intrinsic afferent neurons, extrinsic spinal, and vagal sensory afferents but has not been shown to have an incretin effect through these nerves. GLP-1 and GIP enter the mesenteric lymphatic fluid (MLF) after a meal via the interstitial fluid (IF) from local tissue secretion and/or blood capillaries. Read More

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http://dx.doi.org/10.1152/ajpgi.00189.2019DOI Listing

Antibiotic exposure postweaning disrupts the neurochemistry and function of enteric neurons mediating colonic motor activity.

Am J Physiol Gastrointest Liver Physiol 2020 Jun 11;318(6):G1042-G1053. Epub 2020 May 11.

Department of Physiology, University of Melbourne, Parkville, Victoria, Australia.

The period during and immediately after weaning is an important developmental window when marked shifts in gut microbiota can regulate the maturation of the enteric nervous system (ENS). Because microbiota-derived signals that modulate ENS development are poorly understood, we examined the physiological impact of the broad spectrum of antibiotic, vancomycin-administered postweaning on colonic motility, neurochemistry of enteric neurons, and neuronal excitability. The functional impact of vancomycin on enteric neurons was investigated by Ca imaging in reporter mice to characterize alterations in the submucosal and the myenteric plexus, which contains the neuronal circuitry controlling gut motility. Read More

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http://dx.doi.org/10.1152/ajpgi.00088.2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7311661PMC

Lipopolysaccharides transport during fat absorption in rodent small intestine.

Am J Physiol Gastrointest Liver Physiol 2020 Jun 11;318(6):G1070-G1087. Epub 2020 May 11.

Greater Los Angeles Veterans Affairs Healthcare System, Los Angeles, California.

Lipopolysaccharides (LPS) are potent pro-inflammatory molecules that enter the systemic circulation from the intestinal lumen by uncertain mechanisms. We investigated these mechanisms and the effect of exogenous glucagon-like peptide-2 (GLP-2) on LPS transport in the rodent small intestine. Transmucosal LPS transport was measured in Ussing-chambered rat jejunal mucosa. Read More

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http://dx.doi.org/10.1152/ajpgi.00079.2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7311662PMC

CORRIGENDUM.

Authors:

Am J Physiol Gastrointest Liver Physiol 2020 May;318(5):G988

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http://dx.doi.org/10.1152/ajpgi.zh3-7785corr.2020DOI Listing

Experimental analysis of T cell epitopes for designing liver cancer vaccine predicted by system-level immunoinformatics approach.

Am J Physiol Gastrointest Liver Physiol 2020 Jun 4;318(6):G1055-G1069. Epub 2020 May 4.

Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People's Republic of China.

Liver cancer is a worldwide disease, and, currently, due to the poor prognostic and therapeutic options of liver cancer, we investigated the T cell epitopes as potential therapeutic vaccine candidates to get the benefit of experimental processes and utilize the complete ability of the immune system compared with other artificial ex vivo proliferation of T cells. Activation of T cells targets and kills several tumors, developing a strong rationale for the improvement of immunotherapeutic strategies to cancer therapy. To predict T cell epitopes for liver cancer, we designed a comprehensive immunoinformatics framework involving data mining, immunogenicity prediction, functional proteomic analysis, conservation studies, molecular modeling, and in vivo validation analysis. Read More

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http://dx.doi.org/10.1152/ajpgi.00068.2020DOI Listing
June 2020
3.798 Impact Factor

Immune modulating effects of additional supplementation of estradiol combined with testosterone in murine testosterone-deficient NAFLD model.

Am J Physiol Gastrointest Liver Physiol 2020 Jun 4;318(6):G989-G999. Epub 2020 May 4.

Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan.

Nonalcoholic fatty liver disease (NAFLD) is associated with testosterone deficiency. However, NAFLD patients generally do not respond to treatment with testosterone alone. We investigated the innate immune mechanisms underlying the effects of treatment with testosterone alone, estrogen alone, or combined testosterone and estrogen on high-fat diet (HFD)-induced NAFLD due to testosterone deficiency. Read More

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http://dx.doi.org/10.1152/ajpgi.00310.2019DOI Listing

HDAC6-dependent ciliophagy is involved in ciliary loss and cholangiocarcinoma growth in human cells and murine models.

Am J Physiol Gastrointest Liver Physiol 2020 Jun 27;318(6):G1022-G1033. Epub 2020 Apr 27.

The Hormel Institute, University of Minnesota, Austin, Minnesota.

Reduced ciliary expression is reported in several tumors, including cholangiocarcinoma (CCA). We previously showed primary cilia have tumor suppressor characteristics, and HDAC6 is involved in ciliary loss. However, mechanisms of ciliary disassembly are unknown. Read More

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http://dx.doi.org/10.1152/ajpgi.00033.2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7311663PMC

Letter to Editor: Takeda-G protein receptor-5 signaling mitigates parenteral nutrition-associated liver disease: public health impact.

Authors:
Saumya Pandey

Am J Physiol Gastrointest Liver Physiol 2020 May;318(5):G928-G929

Department of Clinical Research, Indira-IVF Hospital, Udaipur, India.

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http://dx.doi.org/10.1152/ajpgi.00073.2020DOI Listing

Reply to "Letter to Editor: Takeda-G Protein Receptor-5 signaling mitigates parenteral nutrition-associated liver disease: public health impact".

Authors:
Joseph F Pierre

Am J Physiol Gastrointest Liver Physiol 2020 May;318(5):G930

Department of Pediatrics, University of Tennessee Health Science Center, Memphis, Tennessee.

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http://dx.doi.org/10.1152/ajpgi.00080.2020DOI Listing

Dopamine D2 receptor activator quinpirole protects against trypsinogen activation during acute pancreatitis via upregulating HSP70.

Am J Physiol Gastrointest Liver Physiol 2020 Jun 20;318(6):G1000-G1012. Epub 2020 Apr 20.

Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Trypsinogen activation is the hallmark of acute pancreatitis (AP) independent of intra-acinar NF-κB activation and inflammation. We previously found that dopamine (DA) receptor 2 (DRD2) activation controls inflammation during AP via PP2A-dependent NF-κB activation. In this study, we sought to examine whether DRD2 signaling mediates trypsinogen activation and the underlying mechanisms. Read More

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http://dx.doi.org/10.1152/ajpgi.00354.2019DOI Listing
June 2020
3.798 Impact Factor

Microbiota-neuroimmune cross talk in stress-induced visceral hypersensitivity of the bowel.

Am J Physiol Gastrointest Liver Physiol 2020 Jun 20;318(6):G1034-G1041. Epub 2020 Apr 20.

Tytgat Institute for Liver and Intestinal Research, Amsterdam University Medical Centers, Amsterdam, The Netherlands.

Visceral hypersensitivity of the lower gastrointestinal tract, defined as an increased response to colorectal distension, frequently prompts episodes of debilitating abdominal pain in irritable bowel syndrome (IBS). Although the pathophysiology of IBS is not yet fully elucidated, it is well known that stress is a major risk factor for development and acts as a trigger of pain sensation. Stress modulates both immune responses as well as the gut microbiota and vice versa. Read More

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http://dx.doi.org/10.1152/ajpgi.00196.2019DOI Listing

Pharmacological activation of TGR5 promotes intestinal growth via a GLP-2-dependent pathway in mice.

Am J Physiol Gastrointest Liver Physiol 2020 May 20;318(5):G980-G987. Epub 2020 Apr 20.

Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Glucagon-like peptide (GLP)-1 and -2-secreting L cells have been shown to express the bile acid receptor Takeda G protein-receptor-5 (TGR5) and increase secretion upon receptor activation. Previous studies have explored GLP-1 secretion following acute TGR5 activation, but chronic activation and GLP-2 responses have not been characterized. In this study, we aimed to investigate the consequences of pharmacological TGR5 receptor activation on L cell hormone production in vivo using the specific TGR5 agonist RO5527239 and the GLP-2 receptor knockout mouse. Read More

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http://dx.doi.org/10.1152/ajpgi.00062.2020DOI Listing

Gut leakage enhances sepsis susceptibility in iron-overloaded β-thalassemia mice through macrophage hyperinflammatory responses.

Am J Physiol Gastrointest Liver Physiol 2020 May 20;318(5):G966-G979. Epub 2020 Apr 20.

Faculty of Medicine, Department of Microbiology, Chulalongkorn University, Bangkok, Thailand.

Iron overload induces intestinal-permeability defect (gut leakage), and gut translocation of organismal molecules might enhance systemic inflammation and sepsis severity in patients with thalassemia (Thal). Hence, iron administration in Hbb mice, heterozygous β-globin-deficient Thal mice, was explored. Oral iron administration induced more severe secondary hemochromatosis and gut leakage in Thal mice compared with wild-type (WT) mice. Read More

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http://dx.doi.org/10.1152/ajpgi.00337.2019DOI Listing

Changes in specific esophageal neuromechanical wall states are associated with conscious awareness of a solid swallowed bolus in healthy subjects.

Am J Physiol Gastrointest Liver Physiol 2020 May 13;318(5):G946-G954. Epub 2020 Apr 13.

Department of Gastroenterology and Hepatology, College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia.

Esophageal neuromechanical wall states are the physical manifestations of circular muscle inhibition and contraction resulting from neural inputs and leading to bolus propulsion. A novel method infers esophageal neuromechanical wall states through simultaneous determination of pressure and diameter in vivo using impedance manometry. We hypothesized that changes in esophageal neuromechanical wall states relate to conscious awareness of esophageal bolus passage ("bolus perception"). Read More

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http://dx.doi.org/10.1152/ajpgi.00235.2019DOI Listing

Mechanical roles of anterograde and retrograde intestinal peristalses after feeding in a larval fish ().

Am J Physiol Gastrointest Liver Physiol 2020 Jun 13;318(6):G1013-G1021. Epub 2020 Apr 13.

Department of Finemechanics, Graduate School of Engineering, Tohoku University, Sendai, Japan.

Transport in gut is important, not only for digestion, metabolism, and nutrient uptake, but also for microbiotic circumstance in the digestive tract; however, the effects of mixing and pumping in the intestine have not been fully clarified. Therefore, in this study, we quantitatively explored intestinal mixing and pumping, represented using a dispersion coefficient and pressure rise in zebrafish larvae, which is a model organism for vertebrate digestive studies, over time by measuring transport phenomena after feeding. Here we provide the first quantitative evidence of the roles of anterograde and retrograde intestinal peristalses in the larval fish of after feeding in terms of digestive pumping and mixing functions by an in vivo imaging of intestinal propagation waves in the larval intestine. Read More

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http://dx.doi.org/10.1152/ajpgi.00165.2019DOI Listing

Small molecules, big effects: microbial metabolites in intestinal immunity.

Am J Physiol Gastrointest Liver Physiol 2020 May 6;318(5):G907-G911. Epub 2020 Apr 6.

Department of Microbiology, University of Pennsylvania, Philadelphia, Pennsylvania.

The mammalian intestine is host to a vast number of microbial organisms. The immune system must balance tolerance with innate and adaptive defense mechanisms to maintain homeostasis with the microbial community. Interestingly, microbial metabolites have been shown to play a role in shaping the host immune response, thus assisting with adaptations that have significant implications for human health and disease. Read More

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http://dx.doi.org/10.1152/ajpgi.00263.2019DOI Listing

Human intestinal enteroids as a model of -induced enteritis.

Am J Physiol Gastrointest Liver Physiol 2020 May 30;318(5):G870-G888. Epub 2020 Mar 30.

Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas.

is an important nosocomial pathogen that produces toxins to cause life-threatening diarrhea and colitis. Toxins bind to epithelial receptors and promote the collapse of the actin cytoskeleton. toxin activity is commonly studied in cancer-derived and immortalized cell lines. Read More

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http://dx.doi.org/10.1152/ajpgi.00045.2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7272722PMC

Fermentable fibers induce rapid macro- and micronutrient depletion in Toll-like receptor 5-deficient mice.

Am J Physiol Gastrointest Liver Physiol 2020 May 23;318(5):G955-G965. Epub 2020 Mar 23.

Department of Physiology and Pharmacology, University of Toledo College of Medicine and Life Sciences, Toledo, Ohio.

Functional fermentable fibers are considered essential for a healthy diet. Recently, we demonstrated that gut microbiota dysbiotic mice fed an inulin-containing diet (ICD) developed hepatocellular carcinoma (HCC) within 6 mo. In particular, a subset of Toll-like receptor 5-deficient (T5KO) mice prone to HCC exhibited rapid onset of hyperbilirubinemia (HB) and cholemia; these symptoms provide rationale that ICD induces cholestasis. Read More

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http://dx.doi.org/10.1152/ajpgi.00349.2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7276927PMC
May 2020
3.798 Impact Factor