American Journal of Physiology. Gastrointestinal and Liver Physiology

Serotonin is a highly conserved and ubiquitous signalling molecule involved in a vast variety of biological processes. Approximately 90% of serotonin is produced in the gastrointestinal tract, where it is suggested to act as a prominent regulatory molecule in the inflammatory bowel diseases (IBD) Crohn's disease (CD) and ulcerative colitis (UC). Extracellular and circulating serotonin levels are thought to be elevated during intestinal inflammation, but the underlying mechanisms has been poorly understood. The data on human material is limited, contradictory and in need of further investigation and substantiating...

Vertical sleeve gastrectomy (VSG) is the best current therapy for remission of obesity and its co-morbidities. It is understood to alter the enterohepatic circulation of bile acids in vivo. Fibroblast growth factor 19 (FGF19) in human and its murine orthologue Fgf15 plays a pivotal role in this bile acid driven enterohepatic signaling. The present study evaluated the metabolic outcomes of VSG in Fgf15 deficient mice. 6-8 weeks old male wildtype mice (WT) and Fgf15 deficient mice (KO) were fed a high fat diet (HFD) for 8 weeks...

The enterohepatic circulation of bile acids comprises a tightly regulated process of hepatic bile acid secretion, intestinal reabsorption and transport back to the liver. Disruption of this process has significant consequences for both gastrointestinal, liver and whole-body homeostasis and therefore offers opportunities for therapeutic intervention. In this review we discuss the effects of (pharmacological) interruption of the enterohepatic circulation at different levels. Recently, several studies have been published on ileal interruption of the enterohepatic circulation of bile acids, targeting the apical-sodium dependent bile acid transporter (ASBT, SLC10A2), as therapy for various diseases...

Advances in molecular biology that identified the many carrier-mediated organic anion transporters and advances in microscopy that have provided a more detailed anatomy of the canalicular conduit provide for an updating of the concept of osmotically determined canalicular flow. For the most part water flow is not trans-membrane but via specific pore proteins in both the hepatocyte and the tight junction. These pores independently regulate the rate at which water flows in response to and osmotic gradient and therefore are determinants of canalicular bile acid concentration...

Circadian rhythms are biological systems that synchronize cellular circadian oscillators with the organism's daily feeding-fasting or rest-activity cycles in mammals. Circadian rhythms regulate nutrient absorption and utilization at the cellular level, and are closely related to obesity and metabolic disorders. Bile acids are important modulators that facilitate nutrient absorption and regulate energy metabolism. Here, we provide an overview of the current connections and future perspectives between the circadian clock and bile acids metabolism as well as related metabolic diseases...

Altered intestinal permeability plays a role in many pathologic conditions. Intestinal permeability is a component of the intestinal barrier. This barrier is a dynamic interface between the body and the food and pathogens that enter the gastrointestinal tract. Therefore, dietary components can directly affect this interface, and many metabolites produced by the host enzymes or the gut microbiota can act as signaling molecules or exert direct effects on this barrier. Our aim was to examine the effects of diet components on the intestinal barrier in health and disease states...

Recent studies on humans and their key experimental model, the mouse, have begun to uncover the importance of gastrointestinal (GI) microbiota and Enteric Nervous System (ENS) interactions during developmental windows spanning from conception to adolescence. Disruptions in GI microbiota and ENS during these windows by environmental factors particularly antibiotic exposure have been linked to increased susceptibility of the host to several diseases. Mouse models have provided new insights to potential signalling factors between the microbiota and ENS...

Pancreatic cancer (PC) is a malignant tumor that is difficult to diagnose and treat. Circular RNAs (circRNAs) are biomarkers that may be used to diagnose certain cancers or act as targets for cancer treatment. We aimed to explore the functions of human circular RNA 001587 (hsa_circRNA_001587) on the progression of PC and the underlying mechanism. The expression pattern of hsa_circRNA_001587 and microRNA-223 (miR-223) in PC tissues and cells was determined by RT-qPCR. Dual-luciferase reporter gene assay, RNA-pull down, Argonaute 2 (AGO2) immunoprecipitation assay, and Northern blot analysis were applied to verify the binding relationships among hsa_circRNA_001587, miR-223 and solute carrier family 4 member 4 (SLC4A4)...

Capsaicin powerfully evokes the swallowing reflex and is a known therapeutic agent for improving dysphagia and preventing aspiration pneumonia. However, the role of capsaicin-sensitive nerves in the initiation of swallowing evoked by various natural stimuli remains unclear. To explore this question, we blocked laryngeal capsaicin-sensitive nerves following the co-application of QX-314 and capsaicin (QX/Cap), and investigated the effects on swallowing evoked by mechanical and chemical stimulation in anesthetized rats...

BACKGROUND AND AIMS: Severe acute pancreatitis (SAP) includes persistent systemic inflammation (SIRS) and multi-organ failure (MOF). The mechanism of transition from SIRS to MOF is unclear. We developed a fluid compartment model and used clinical data to test predictions. METHODS: The model includes vascular, interstitial and "third space" compartments with variable permeability of plasma proteins at the capillaries. Consented patients from UPMC Presbyterian Hospital were studied...

Portal and hepatic circulation can now be safely accessed using endoscopic ultrasound (EUS). EUS-guided needle access of the portal vein is performed clinically at select tertiary centers for measurement of portal pressure gradients in patients with chronic liver disease and sampling of portal venous thrombus to diagnose malignancy. We propose that this novel clinical technique can be applied in research studies to allow blood collection from and profiling of portal and hepatic circulation. In this technical report, we present and highlight the technical aspects, feasibility and safety of EUS - guided portal venous blood collection...

The first contractile waves in the developing embryonic gut are purely myogenic, they only involve smooth muscle. Here, we provide evidence for a transition from smooth-muscle to Interstitial Cell of Cajal (ICC) driven contractile waves in the developing chicken gut. In-situ hybridization staining for ANO1, a known ICC marker, shows that ICCs are already present throughout the gut as from embryonic day 7 (E7). We devised a protocol to reveal ICC oscillatory and propagative calcium activity in embryonic gut whole-mount and find that the first steady calcium oscillations in ICCs occur at E14...

Parkinson's diseases (PD) is a common neurodegenerative disorder characterized by motor and gastrointestinal (GI) deficits. Despite its prevalence, the pathophysiology of PD is not well understood. Recent studies highlight the role of gut microbiota in neurological disorders. In this review, we summarize the potential role of gut microbiota in the pathophysiology of PD. We first describe how gut microbiota can be influenced by factors predisposing individuals to PD such as environmental toxins, aging, and host genetics...

Obesity is linked to non-alcoholic steatohepatitis. PPARα regulates lipid metabolism. CYP2A5 is a potential antioxidant and CYP2A5 induction by ethanol is CYP2E1-dependent. High fat diet (HFD)-induced obesity and steatosis are more severe in CYP2A5 knockout (cyp2a5-/-) mice than in wild-type mice although PPARα is elevated in cyp2a5-/- mice. To examine why the up-regulated PPARα failed to prevent the enhanced steatosis in cyp2a5-/- mice, we abrogate the up-regulated PPARα in cyp2a5-/- mice by cross-breeding cyp2a5-/- mice with PPARα knockout (pparα-/-) mice to create pparα-/-/cyp2a5-/- mice...

Regular aerobic exercise has numerous benefits on human physiology, arguably by serving as a hormetic stressor resulting in positive adaptations over time. It has long been known that aerobic exercise at a variety of intensities and durations induces intestinal permeability, which is a feature of many pathologies of the gastrointestinal tract and metabolic diseases. Given the health benefits of exercise, it seems unlikely that intestinal permeability induced by exercise outweighs the positive adaptations. In fact, a growing body of evidence suggests adoption of exercise regimens lasting weeks to months improves indicators of intestinal permeability...

Small intestinal neuroendocrine tumors (SI-NET) are serotonin-secreting well-differentiated neuroendocrine tumors of putative enterochromaffin (EC) cell origin. Recent studies recognize a subset of EC cells that is label-retaining at the +4 position in the crypt and functions as a reserve intestinal stem cell (ISC). Importantly, this +4 reserve EC cell subset not only contributes to regeneration of the intestinal epithelium during injury and inflammation but also to basal crypt homeostasis at a constant rate...

Obesity and type 2 diabetes are frequently complicated by excess fat accumulation in the liver, which is known as nonalcoholic fatty liver disease (NAFLD). In this context, liver steatosis develops as a result of the deregulation of pathways controlling de novo lipogenesis and fat catabolism. Recent evidences suggest the clinical relevance of a reduction in the activity of lysosomal acid lipase (LAL), which is a key enzyme for intracellular fat disposal, in patients with NAFLD. In this review, we provided a comprehensive overview of the critical steps in hepatic fat metabolism and alterations in these pathways in NAFLD, with a special focus on lipophagy and LAL activity...

Nonalcoholic fatty-liver disease (NAFLD) is the most common cause of liver-related mortality. NAFLD is associated with obesity, hepatic fat accumulation and insulin-resistance, all of which contribute to its pathophysiology. Weight-loss is the main therapy for NAFLD and metabolic surgery is the most effective treatment for morbid obesity and its metabolic comorbidities. Although has been reported that Roux-en-Y gastric bypass can reverse NAFLD, it is unclear if such effects result from reduced weight, from a less calorie-intake or from the direct influence of surgery on mechanisms contributing to NAFLD...

Fecal continence is maintained by several mechanisms including anatomical factors, anorectal sensation, rectal compliance, stool consistency, anal muscle strength, mobility, and psychological factors. The homeostatic balance is easily disturbed, resulting in symptoms including fecal incontinence and constipation. Current technologies for assessment of anorectal function have limitations. Overlap exist between data obtained in different patient groups, and there is lack of correlation between measurements and symptoms...

The loss of the intestinal Na+ /H+ exchanger isoform 8 (NHE8) results in an ulcerative colitis-like condition with reduction of mucin production and dysbiosis, indicating that NHE8 plays an important role in intestinal mucosal protection. The aim of this study was to investigate the potential rebalance of the altered microbiota community of NHE8-deficient mice via fecal microbiota transplantation (FMT) and feeding probiotic VSL#3. We also aimed to stimulate mucin production by sodium butyrate administration via enema...