American Journal of Physiology. Gastrointestinal and Liver Physiology

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. As SARS-CoV-2 infects the human body through the combination of ACE2 in the gastrointestinal tract, the mechanism underlying the gastrointestinal symptoms may involve damage to the intestinal mucosal barrier and promotion of the production of inflammatory factors, causing cytokine storms...

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...

25-Hydroxyvitamin D3 -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. 25OHD) inside the intestinal lumen. We hypothesized that 25OHD-Gluc would elicit a VDR-dependent mRNA response in the colon after cleavage by gut microbiota. The activity of 25OHD-Gluc was investigated by measuring expression of cytochrome P450 24A1 (Cyp24) mRNA both in vitro and in vivo...

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. Wnt, Notch, and other epithelial control signals feed into these cis-regulatory DNA elements, which are also common loci of polymorphisms and mutations that confer disease risk...

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...

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. We therefore investigated whether the administration of broad spectrum antibiotics in conjunction with SBS in zebrafish (ZF) would replicate these systemic effects observed in humans in order to identify potentially druggable targets to aid in the management of SBS and resulting IFALD...

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. METHODS: In an observational before-and-after intervention study, the ureagenesis capacity was quantified by functional hepatic nitrogen clearance (FHNC) in nine CHC patients with cirrhosis and ten healthy volunteers...

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. We hypothesized that OCA administration during hypercholanemic pregnancy will improve maternal and fetal bile acid and lipid profiles...

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. This study uses a longitudinal study design to compare the effects of a narrow-spectrum (ridinilazole) or broad-spectrum antibiotic (vancomycin) on intestinal bile acid profiles and their associations with gut bacteria over the course of C...

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. One hallmark of NASH are changes in mitochondrial morphology and function that are accompanied by a blocked flow of electrons in the respiratory chain, which increases formation of mitochondrial reactive oxygen species in a self-perpetuating vicious cycle...

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. Cholesterol saturation index of patients with gallstone was significantly higher than that of the controls...

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. Cyclic adenosine monophosphate (cAMP)-activated ion transport was examined in the presence or absence of SGK1 and PI3K inhibitors...

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. Active K+ absorption was determined by measuring 86 Rb+ (K+ surrogate) fluxes in colonic epithelia mounted under voltage clamp conditions...

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. Female pigs (n=12; 2-3 months old; 25.6 ± 2.2 kg) had surgically-implanted catheters across portal-drained viscera (PDV), splanchnic area (SPL), liver, kidney, and hindquarter muscle...

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. GKN1/GKN2 loss is highly co-ordinated, with both genes showing parallel downregulation during human and mouse GC development, suggesting joint transcriptional control...

BACKGROUND AND AIMS: Hyaluronic acid (HA), a glycosaminoglycan in the extracellular matrix, binds to CD44 and TLR4. We previously demonstrated that TLR4 predominately mediated HA stimulation of Lgr5+ stem cell proliferation, crypt fission and intestinal growth in postnatal mice. Here we address which cell type expresses the relevant TLR4 in driving intestinal growth and the downstream events from TLR4 activation. METHODS: Studies were done in 14-day-old mice: wild type (WT), mice deficient in either cyclooxygenase2 (COX2), myeloid cell TLR4 or epithelial cell EGFR...

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...

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 utilisation...

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. While there are isolated examples of xenometabolites influencing host health and disease, wide-scale characterization of these metabolites remain limited. We developed a metabolomics platform ("XenoScan") using liquid chromatography-mass spectrometry to characterize a range of known and suspected xenometabolites and their derivatives...

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. We therefore aimed to explore the ileal transcriptome to gain knowledge about CD. METHODS: We performed whole transcriptome gene expression analysis on ileocecal resections from CD patients and inflammatory bowel disease-free controls, as well as on a CD-independent cohort to replicate selected results...