Showing papers in "American Journal of Physiology-gastrointestinal and Liver Physiology in 2019"
TL;DR: Application of immunohistochemical markers of hepatocyte injury may serve as a more objective tool for distinguishing NASH from NAFL, facilitating improved resolution of hepatic molecular changes associated with progression of NAFLD.
Abstract: Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in Western countries. NAFLD is associated with the metabolic syndrome and can progress to the more serious form, nonalcohol...
143 citations
TL;DR: It is concluded thatExosomes in bovine milk alter microbial communities in non-bovine species, suggesting that exosomes and their cargos participate in the crosstalk between bacterial and animal kingdoms.
Abstract: This is the first report that exosomes from bovine milk alter microbial communities in mice. This report suggests that the gut microbiome facilitates cell-to-cell communication by milk exosomes acr...
75 citations
TL;DR: It is suggested that HFD promotes colitis by aggravating mucosal oxidative stress, which rapidly drives mucosal inflammation and increases intestinal mucosal barrier permeability.
Abstract: This study demonstrates high-fat diet feeding promotes colitis in a 2,4,6-trinitrobenzenesulfonic acid-induced experimental colitis model in mice. The underlying mechanism is that high-fat diet ind...
65 citations
TL;DR: This work defines the components of the intestinal barrier, reviews available modalities to assess its structure and function in humans, and provides a conceptual framework by which evidence could be developed to support the notion that diet can reinforce human intestinal barrier function to restore normal function and potentially reduce the risk for disease.
Abstract: A reduction in intestinal barrier function is currently believed to play an important role in pathogenesis of many diseases, as it facilitates passage of injurious factors such as lipopolysaccharid...
63 citations
TL;DR: It is discussed how incorporating the germ-organ concept, ecological assumptions and immunological principles into a theoretical framework for microbiota research provides a functional definition for dysbiosis.
Abstract: Advances in data collection technologies reveal that an imbalance (dysbiosis) in the composition of host-associated microbial communities (microbiota) is linked to many human illnesses. This associ...
54 citations
TL;DR: This is the first study revealing that microRNA- 23a (miR-23a) promotes hepatic fibrosis through the phosphatase and tensin homolog/phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin/Snail signaling pathway, and long noncoding RNA (lncRNA) growth arrest-specific transcript 5 (GAS5) can act as a sponge platform for miR-
Abstract: This is the first study revealing that microRNA-23a (miR-23a) promotes hepatic fibrosis through the phosphatase and tensin homolog/phosphatidylinositol 3-kinase/protein kinase B/mammalian target of...
52 citations
TL;DR: LncRNA PVT1 competitively binds to miR-214-3p to up-regulate the expression of IRS1 through activation of the PI3K/Akt signaling pathway, thus accelerating CRC progression, and is suggested to be a potential target of therapeutic strategies for CRC treatment.
Abstract: This study mainly suggests that long noncoding (lnc)RNA plasmacytoma variant translocation 1 (PVT1) is a downregulated lncRNA in colorectal cancer (CRC), accelerating CRC progression. Strikingly, l...
51 citations
TL;DR: The small and large intestine have a very high paracellular Pi permeability that may favor monovalent Pi fluxes and allows efficient uptake of Pi even in the absence of active transcellular Pi uptake.
Abstract: The paracellular permeability for phosphate is high along the entire axis of the small and large intestine. There is a slight preference for monovalent phosphate. Paracellular phosphate fluxes do n...
49 citations
TL;DR: It is demonstrated that RDX8940, a potent, selective, minimally systemic oral TGR5 agonist, improves liver steatosis and insulin sensitivity in a mouse model of NAFLD and does not inhibit gallbladder emptying in mice, indicating that RDx8940 may have therapeutic potential in patients withNAFLD/NASH.
Abstract: Takeda G protein-coupled receptor 5 (TGR5) agonists have potential as a treatment for nonalcoholic steatohepatitis and nonalcoholic fatty liver disease (NAFLD) but have until now been associated wi...
49 citations
TL;DR: It is found that feeding LR did not affect clinical phenotype or inflammatory biomarkers in plasma and stool, but LR increased the proportion of Foxp3+ regulatory T cells (Tregs) in the intestine and exerted a major impact on the plasma metabolome.
Abstract: Oral administration of Lactobacillus reuteri DSM 17938 (LR) to healthy breastfed mice promotes intestinal immune tolerance and is linked to proliferation of beneficial gut microbiota. LR upregulate...
46 citations
TL;DR: The effects of multiple nitric oxide-dependent and -independent pharmaceutical agents on fenestrations of the liver sinusoidal endothelium are demonstrated and indicate that age-related defenestration can be reversed pharmacologically, which has potential translational relevance for dyslipidemia and insulin resistance.
Abstract: We demonstrate the effects of multiple nitric oxide-dependent and -independent pharmaceutical agents on fenestrations of the liver sinusoidal endothelium. Fenestrations are reorganized in response ...
TL;DR: The intestinal microbiome plays a major role in the pathogenesis of liver disease, with a hallmark event being dysbiosis, or an imbalance of pathobionts and beneficial bacteria with the associated...
Abstract: The intestinal microbiome plays a major role in the pathogenesis of liver disease, with a hallmark event being dysbiosis, or an imbalance of pathobionts and beneficial bacteria with the associated ...
TL;DR: Cytoprotective effects of SC79 against TNF-α act through both AKT-mediated activation of NF-κB and upregulation of FLIPL/S, which suggests that SC79 is likely a promising therapeutic agent for ameliorating the development of liver injury.
Abstract: SC79 protects hepatocytes from TNF-α-mediated apoptosis and mice from Gal/LPS-induced liver injury and damage. Cytoprotective effects of SC79 against TNF-α act through both AKT-mediated activation ...
TL;DR: It is suggested that intestinal dysbiosis due to impaired intestinal barrier may be the key cause of metabolic disorders in hyperuricemia mice.
Abstract: Hyperuricemia is associated with many metabolic diseases. However, the underlying mechanism remains unknown. We constructed a hyperuricemic mouse model to explore the relationship between intestina...
TL;DR: Individuals with diabetes after acute pancreatitis have significantly higher intrapancreatic fat percentage, visceral fat volume, and V/S fat volume ratio, and levels of C-reactive protein during AP are significantly associated with VFV, whereas biliary AP is significant associated with intrapANCreaticfat percentage.
Abstract: Individuals with diabetes after acute pancreatitis have significantly higher intrapancreatic fat percentage and visceral fat volume compared with individuals without diabetes after acute pancreatit...
TL;DR: In male cirrhotic Veterans, combat-related PTSD is associated with cognitive impairment, lower microbial diversity, higher pathobionts and lower autochthonous taxa composition and altered gut-brain axis functionality.
Abstract: Posttraumatic stress disorder (PTSD) in veterans with cirrhosis was associated with poor cognitive performance. This was associated with lower gut microbial diversity in PTSD with higher pathobiont...
TL;DR: It is demonstrated that bile acids are potent and direct promoters of colonic glucagon-like-peptide 1 and peptide-YY secretion and provided convincing evidence that basolateral Takeda-G protein-coupled-receptor 5 activation is mediating the effects of bile acid in the colon.
Abstract: By the use of isolated perfused rodent colon preparations we show that bile acids are potent and direct promoters of colonic glucagon-like-peptide 1 and peptide-YY secretion. The study provides con...
TL;DR: Three noninvasive biomarkers that can be used to identify patients with progressive liver fibrosis, monitor response to antifibrotic therapy, and also identify the spontaneous fibrosis regression phenotype are presented.
Abstract: In this study we report two biomarkers of collagen fragments (PRO-C3 and C6M) that are able to identify liver fibrosis progressors while one biomarker (PRO-C5) identified liver fibrosis regressors
TL;DR: It is shown for the first time that the MMP-9-induced increase in intestinal TJ permeability in vitro and in vivo was mediated by the p38 kinase signal transduction pathway upregulation of MLCK gene activity and that therapeutic targeting of these pathways can prevent the M Parliamentary metalloproteinase-9 increase.
Abstract: MMP-9 is highly elevated in patients with IBD. IBD patients have compromised intestinal TJ barrier function manifested by an increase in intestinal permeability and intestinal inflammation. This st...
TL;DR: An overview is provided on the EV classification, biogenesis and secretion pathways which are conserved across cell types, and isolation and characterization methods, and the potential biomarker and therapeutic uses of circulating EVs.
Abstract: Extracellular vesicles (EVs) are membrane-defined nanoparticles released by most cell types. The EVs released by cells may differ quantitatively and qualitatively from physiological states to disea...
TL;DR: Evidence is discussed regarding the role of microbes in promoting CeD, and the specific pathways triggered by microbes that could participate in CeD pathogenesis, to develop optimal microbiota modulating strategies to help prevent CeD.
Abstract: The prevalence of celiac disease (CeD) has increased in the last decades, suggesting a role for environmental factors in addition to gluten. Several cohort studies have shown that different gastroi...
TL;DR: This review focuses on recent advances in understanding of ISC identity, behavior, and regulation during homeostasis and injury-induced repair, as revealed by two major animal models used to study regeneration of the small intestine: Drosophila melanogaster and Mus musculus.
Abstract: The gastrointestinal (GI) tract renews frequently to sustain nutrient digestion and absorption in the face of consistent tissue stress. In many species, proliferative intestinal stem cells (ISCs) a...
TL;DR: Current knowledge on the roles of pancreatic and mucosal enzymes in PC and SM digestion, and its implications in intestinal and liver diseases, bacterial choline metabolism in the gut, and cholesterol absorption are summarized.
Abstract: The digestion of choline phospholipids is important for choline homeostasis, lipid signaling, postprandial lipid and energy metabolism, and interaction with intestinal bacteria. The digestion is mediated by the combined action of pancreatic and mucosal enzymes. In the proximal small intestine, hydrolysis of phosphatidylcholine (PC) to 1-lyso-PC and free fatty acid (FFA) by the pancreatic phospholipase A2 IB coincides with the digestion of the dietary triacylglycerols by lipases, but part of the PC digestion is extended and must be mediated by other enzymes as the jejunoileal brush-border phospholipase B/lipase and mucosal secreted phospholipase A2 X. Absorbed 1-lyso-PC is partitioned in the mucosal cells between degradation and reacylation into chyle PC. Reutilization of choline for hepatic bile PC synthesis, and the reacylation of 1-lyso-PC into chylomicron PC by the lyso-PC-acyl-CoA-acyltransferase 3 are important features of choline recycling and postprandial lipid metabolism. The role of mucosal enzymes is emphasized by sphingomyelin (SM) being sequentially hydrolyzed by brush-border alkaline sphingomyelinase (alk-SMase) and neutral ceramidase to sphingosine and FFA, which are well absorbed. Ceramide and sphingosine-1-phosphate are generated and are both metabolic intermediates and important lipid messengers. Alk-SMase has anti-inflammatory effects that counteract gut inflammation and tumorigenesis. These may be mediated by multiple mechanisms including generation of sphingolipid metabolites and suppression of autotaxin induction and lyso-phosphatidic acid formation. Here we summarize current knowledge on the roles of pancreatic and mucosal enzymes in PC and SM digestion, and its implications in intestinal and liver diseases, bacterial choline metabolism in the gut, and cholesterol absorption.
TL;DR: This mini review focuses on the recent data on the mechanisms of NASH, focusing on lipid mediators and their potential as therapeutic targets in NASH.
Abstract: Nonalcoholic fatty liver disease (NAFLD) comprises a spectrum of histopathological phenotypes ranging from simple steatosis to more severe liver disease associated with cell injury, including nonalcoholic steatohepatitis (NASH), advanced fibrosis, and cirrhosis. Only a subset of patients with NAFLD develop NASH from yet incompletely understood mechanisms. Emerging data suggest lipid species other than triglycerides as contributors to the pathogenesis of NASH. In this mini review, we focus on the recent data on the mechanisms of NASH, focusing on these lipid mediators and their potential as therapeutic targets in NASH.
TL;DR: Histamine-producing Lactobacillus reuteri can suppress development of inflammation-associated colon cancer in an established mouse model and novel strategies for suppression of intestinal inflammation and colorectal neoplasia could be developed.
Abstract: Histamine-producing Lactobacillus reuteri can suppress development of inflammation-associated colon cancer in an established mouse model. The net effects of histamine may depend on the relative act...
TL;DR: It is found that renin was highly induced in colonic biopsies from patients with ulcerative colitis or Crohn's disease, and colonic renin and ANG II levels were markedly increased in a 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis model, indicating that the colonic RAS is activated in colitis.
Abstract: This study demonstrates that the local renin-angiotensin system in the colon is activated in colitis development, which promotes mucosal T helper cell activation through the JAK2/STAT pathway. Thes...
TL;DR: 3-D image data reveal the human pancreatic afferent and efferent innervation patterns and provide the anatomical foundation for future high-definition analyses of neural remodeling in human Pancreas diseases.
Abstract: Modern three-dimensional (3-D) histology with multiplex optical signals identifies the afferent and efferent innervation patterns of human pancreas, which otherwise cannot be defined with standard ...
TL;DR: A mini-review of the physiological mechanisms that mediate sex-dependent disparities in functional gastrointestinal disorders are discussed, including the influence of estrogen on GI motility and sensitivity; and stress modulation of the brain-gut axis.
Abstract: Symptoms of functional gastrointestinal disorders (FGIDs), including fullness, bloating, abdominal pain, and altered gastrointestinal (GI) motility, present a significant clinical problem, with a r...
TL;DR: The combination of CCl4intoxication with WD validate previous data suggesting it as an appropriate model for human NASH, providing a model suitable for further basic research and drug testing.
Abstract: Alcoholic fatty liver disease with significant fibrosis is generated within 7 wk using carbon tetrachloride as a fibrosis accelerator and administering gradually ethanol (up to 16%) in mice. The si...
TL;DR: The data indicate that reactivation of autophagy and lysosome function through the restoration of transcription factor EB contribute to reversal of fatty liver and injury following EtOH withdrawal.
Abstract: Here, using an animal model, we show mechanisms of reversal of fatty liver and injury following ethanol withdrawal. Our data indicate that reactivation of autophagy and lysosome function through th...