Regulation Of Intestinal Function Research Articles

Clostridium butyricum regulates intestinal barrier function via trek1 to improve behavioral abnormalities in mice with autism spectrum disorder

BackgroundAutism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder that has been found to be associated with dysregulation of gastrointestinal functions and gut microbial homeostasis (the so-called “gut-brain axis”). ASD is often accompanied by poor performances in social interaction and repetitive behaviors. Studies on the gut-brain axis provide novel insights and candidate targets for ASD therapeutics and diagnosis. Based on the ASD mice model, this work aims to reveal the mechanisms behind the interaction of intestinal barrier function and probiotics in ASD mouse models.ResultsWe found an altered intestinal barrier in both BTBR T+ Itpr3tf/J (BTBR) and valproic acid (VPA) mice, including increased intestinal permeability, decreased expression of intestinal tight junction proteins (claudin1, claudin3, and occludin), and increased levels of IL-6, TNF-α, and IFN-γ. Based on intestinal microbial alternation, C. butyricum can drive reduced expression of histone deacetylases 1 (HDAC1) and enhanced intestinal barrier function, significantly promoting behavioral abnormalities of ASD in BTBR mice. In parallel, we confirmed that C. butyricum was involved in the regulation of intestinal function by the Trek1 channel, indicating that it is a target of C. butyricum/butyric acid to improve intestinal barrier function in ASD mice.ConclusionsOur finding provides solid evidence for the gut microbiota involved in ASD through the brain-gut axis. In addition, the probiotics C. butyricum hold promise to improve gut health and ameliorate behavioral abnormalities associated with ASD.

Surgery-induced gut microbial dysbiosis promotes cognitive impairment via regulation of intestinal function and the metabolite palmitic amide

BackgroundPerioperative neurocognitive disorders (PND) are the most common postoperative complications with few therapeutic options. Gut microbial dysbiosis is associated with neurological diseases; however, the mechanisms by which the microbiota regulates postoperative gastrointestinal and cognitive function are incompletely understood.MethodsBehavioral testing, MiSeq 16S rRNA gene sequencing, non-target metabolism, intestinal permeability detection, protein assays, and immunofluorescence staining were employed to discern the impacts of surgery on microbial profiles, intestinal barriers, serum metabolism, and the brain. Interventions in mice included fecal microbiota transplantation, the anti-inflammatory agent dexamethasone, Lactobacillus supplementation, indole propionic acid supplementation, and palmitic amide administration.ResultsSurgery-induced cognitive impairment occurs predominantly in aged mice, and surgery-induced alterations in the microbiota composition profile exacerbate intestinal barrier disruption in aged mice. These adverse effects can be mitigated by transferring microbiota from young donors or by bolstering the intestinal barrier function using dexamethasone, Lactobacillus, or indole propionic acid. Moreover, microbiota composition profiles can be restored by transplanting feces from young mice to aged surgical mice, improving neuropathology and cognitive function, and these effects coincide with increased intestinal permeability. Metabolomic screening identified alterations in metabolites in mouse serum after surgery, especially the increase in palmitic amide. Palmitic amide levels in serum and brain can be decreased by transplanting feces from young mice to aged surgical mice. Oral palmitic amide exacerbates cognitive impairment and neuropathological changes in mice.ConclusionsGut microbial dysbiosis in mice after surgery is a key mechanism leading to cognition dysfunction, which disrupts the intestinal barrier and metabolic abnormalities, resulting in neuroinflammation and dendritic spine loss. Intestinal barrier damage and high level of palmitic amide in old mice may be the cause of high incidence of PND in the elderly. Preoperative microbiota regulation and intestinal barrier restoration may be of therapeutic benefit in preventing PND.9Ey9teFKZKXmrKtD72aS7bVideo

A Critical Review of Kaempferol in Intestinal Health and Diseases.

Kaempferol, a secondary metabolite found in plants, is a naturally occurring flavonoid displaying significant potential in various biological activities. The chemical structure of kaempferol is distinguished by the presence of phenyl rings and four hydroxyl substituents, which make it an exceptional radical scavenger. Most recently, an increasing number of studies have demonstrated the significance of kaempferol in the regulation of intestinal function and the mitigation of intestinal inflammation. The focus of the review will primarily be on its impact in terms of antioxidant properties, inflammation, maintenance of intestinal barrier function, and its potential in the treatment of colorectal cancer and obesity. Future research endeavors should additionally give priority to investigating the specific dosage and duration of kaempferol administration for different pathological conditions, while simultaneously conducting deeper investigations into the comprehensible mechanisms of action related to the regulation of aryl hydrocarbon receptor (AhR). This review intends to present novel evidence supporting the utilization of kaempferol in the regulation of gut health and the management of associated diseases.

Nutritional correction after extensive combined bowel resections: new approaches to rehabilitation

Introduction . Metabolic correction of the consequences of extensive (especially combined) intestinal resections requires enormous efforts due to weight loss, a decrease in plasma albumin concentration of less than 30 g/l, electrolyte disorders, organ failure, etc. There are consequences in the form of short small intestine syndrome, postcolectomy syndrome and the combined consequences of resections of the small and large intestine. The most severe changes are after combined thin-thick-intestinal resections, the prevalence of which continues to increase. Nevertheless, the data on the occurrence of combined resections (thin-colon) are very contradictory. Aim . To analyze the effectiveness of nutritional correction programs in SBS syndrome due to extensive combined small-colonic resections and to characterize possible ways of correcting metabolic complications with the help of nutritional correction, taking into account the optimization of absorption in the intestine. Materials and methods . We examined 208 patients with combined extensive resection of the small intestine with right-sided hemicolectomy (65% of men and 35% of women). Metabolic changes, nutritional characteristics and reparation under the influence of nutritional correction in this category of patients are described. Results . Data on the restoration of lost functions are presented, which is based on the analysis of the mechanisms of adaptation and cellular regeneration. Regenerative aspects of hormonal (enteroglucagon) regulation of intestinal functions after its extensive resection and artificial alimentation are closely related. Conclusion . It is advisable to introduce teduglutide into the treatment structure to stimulate rehabilitation absorption processes after extensive combined intestinal resections.

PPARγ activation inhibits endocytosis of claudin-4 and protects against deoxynivalenol-induced intestinal barrier dysfunction in IPEC-J2 cells and weaned piglets

The role of peroxisome proliferator activated receptor gamma (PPARγ) in the regulation of adipocyte differentiation has been well characterized. Besides adipose tissue, PPARγ is also highly expressed in the intestine. However, the functional role of PPARγ in the regulation of intestinal function still remains poorly understood. In the present study, we sought to understand the role of PPARγ activation on regulation of intestinal barrier function in intestinal porcine epithelial cells (IPEC-J2) and weaned piglets exposed to the mycotoxin, deoxynivalenol (DON). PPARγ activation by rosiglitazone and troglitazone, two pharmacological PPARγ ligands, increased the protein expression of tight junction proteins (TJP), claudin-3 and 4. PPARγ inhibition increased endocytosis of claudin-4 which was reversed by its activation with troglitazone. DON exposure decreased the protein expression of TJP, and also significantly suppressed PPARγ transcriptional activity. Interestingly, PPARγ activation reversed the reduction of claudin-3 and 4 caused by DON in vitro and in vivo. PPARγ activation also partially restored the transepithelial electrical resistance (TEER) and reduced the permeability of fluorescein isothiocyanate-dextran (FITC-dextran) that have been negatively impacted by DON. These effects were lost in the presence of a specific PPARγ antagonist or in PPARγ knockout cells, confirming the importance of PPARγ in the regulation of intestinal barrier function and integrity. Likewise, in weaned pigs exposed to DON, the PPARγ agonist pioglitazone mitigated the impaired villus-crypt morphology caused by DON. Therefore, pharmacological and natural bioactive compounds with PPARγ stimulatory activities could be effective in preventing DON-induced gut barrier dysfunction.

PSVIII-B-14 Peroxisome Proliferator-Activated Receptor Gamma Activation Protects Against Deoxynivalenol-Induced Intestinal Barrier Dysfunction in Jejunal Ipec-J2 Cells

Abstract The role of peroxisome proliferator activated receptor gamma (PPARg) in the regulation of lipid metabolism, adipocyte differentiation and inflammatory response has been well characterized. Besides adipose tissue, PPARg is also highly expressed in the intestine. However, the functional role of PPARg in the regulation of intestinal function still remains poorly understood. In the present study we sought to understand the role of PPARg activation on intestinal barrier function in IPEC-J2 cells exposed (2mM, 24hr) to the mycotoxin, deoxynivalenol (DON). PPARg activation by rosiglitazone and troglitazone dose-dependently increased (P < 0.05) the protein expression of tight junction proteins (TJP), claudin-3 and 4. On the contrary, the protein abundance of claudin-3 and 4 was dose-dependently decreased by PPARg antagonist, T0070907. DON exposure decreased the protein expression of TJP, and also significantly suppressed (P < 0.05) PPARg transcriptional activity. Consistent with the therapeutic benefits of PPARg agonists, pretreatment of cells with PPARg agonists (40 mM) reversed (P < 0.05) the reduction of claudin-3 and 4 induced by DON exposure. Immunofluorescence analysis showed that the decreased membrane presence of claudin-4 and ZO-1 induced by DON was also reversed by troglitazone. Effect of PPARg activation also included partial restoration of transepithelial electrical resistance (TEER) and reduction of FITC-dextran permeability that have been disrupted by DON. However, the protective effects of PPARg agonist against DON exposure was abolished by PPARg antagonist, confirming the importance of PPARg in the observed effects of the agonists. This shows the importance of PPARg activity in the maintenance of intestinal epithelial cells homeostasis and barrier function, especially during periods of metabolic stress induced by the mycotoxin, DON. Therefore, pharmacological and natural bioactive compounds with PPARg agonist activity could be effective in preventing DON-induced gut barrier dysfunction in vivo.

Inhibitory Effect of Lactobacillus plantarum KFY02 Fermented Lemon Juice on Obesity and Intestinal Regulation in Mice Fed with High-fat Diet

The purpose of this study was to observe the fat reducing effect of lemon juice fermented by Lactobacillus plantarum KFY02 and its regulation on intestinal flora. This study induced obesity in mice through the establishment of high-fat diet, the experimental mice were divided into normal group, model group, Lactobacillus plantarum KFY02 group, unfermented lemon juice group and fermented lemon juice group, and biochemical kits, section observation and quantitative PCR were used to detect the related indexes of mouse serum and tissue, and the composition of intestinal microorganisms was observed by detecting the expression of microorganisms in feces. The results showed that Lactobacillus plantarum KFY02, unfermented lemon juice and fermented lemon juice could effectively reduce the body weight of obese mice, reduce the organ index of liver and epididymal adipose tissue in obese mice, and reduce the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AKP), total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C) and raise high density lipoprotein cholesterol (HDL-C) in serum and liver tissue of obese mice, and also could increase the contents of total cholesterol (TC), triglyceride (TG) and total protein (TP) in mouse feces. H&E pathological observation showed that Lactobacillus plantarum KFY02, unfermented lemon juice and fermented lemon juice could also reduce liver tissue lesions and adipocyte enlargement and accumulation caused by obesity. qPCR results showed that Lactobacillus plantarum KFY02, unfermented lemon juice and fermented lemon juice could up-regulate PPAR-α, CPT-1, LPL, CYP7A1 and down-regulate C/EBPα, PPAR-γ mRNA expression in liver tissue of obese mice induced by high fat diet, meanwhile, they could also up-regulate the expression of Bacteroidetes, Lactobacillus sp., Bifidobacterium sp. and down-regulate the expression of Firmicutes. These results showed that Lactobacillus plantarum KFY02, unfermented lemon juice and fermented lemon juice could reduce fat in mice, and the effect of fermented lemon juice was the best. The fat reduction effect of fermented lemon juice on mice was directly related to its regulation of intestinal function and microbial composition. It could be seen that lemon juice fermented by Lactobacillus plantarum KFY02 had good lipid-lowering and intestinal regulation in obese mice.

The Influence of Bisphenol A (BPA) on the Occurrence of Selected Active Substances in Neuregulin 1 (NRG1)-Positive Enteric Neurons in the Porcine Large Intestine.

Bisphenol A (BPA) is a substance used in the manufacture of plastics which shows multidirectional adverse effects on living organisms. Since the main path of intoxication with BPA is via the gastrointestinal (GI) tract, the stomach and intestine are especially vulnerable to the impact of this substance. One of the main factors participating in the regulation of intestinal functions is the enteric nervous system (ENS), which is characterized by high neurochemical diversity. Neuregulin 1 (NRG1) is one of the lesser-known active substances in the ENS. During the present study (performed using the double immunofluorescence method), the co-localization of NRG1 with other neuronal substances in the ENS of the caecum and the ascending and descending colon has been investigated under physiological conditions and after the administration of BPA. The obtained results indicate that NRG1-positive neurons also contain substance P, vasoactive intestinal polypeptide, a neuronal isoform of nitric oxide synthase and galanin and the degree of each co-localization depend on the type of enteric plexus and the particular fragment of the intestine. Moreover, it has been shown that BPA generally increases the degree of co-localization of NRG1 with other substances.

Centrally administered butyrate improves gut barrier function, visceral sensation and septic lethality in rats

Short chain fatty acids readily crosses the gut-blood and blood–brain barrier and acts centrally to influence neuronal signaling. We hypothesized that butyrate, a short-chain fatty acid produced by bacterial fermentation, in the central nervous system may play a role in the regulation of intestinal functions. Colonic permeability and visceral sensation was evaluated in rats. Septic lethality was evaluated in a sepsis model induced by subcutaneous administration of both lipopolysaccharide and colchicine. Intracisternal butyrate dose-dependently improved colonic hyperpermeability and visceral nociception. In contrast, subcutaneous injection of butyrate failed to change it. Intracisternal orexin 1 receptor antagonist or surgical vagotomy blocked the central butyrate-induced improvement of colonic hyperpermeability. The improvement of intestinal hyperpermeability by central butyrate or intracisternal orexin-A was blocked by cannabinoid 1 or 2 receptor antagonist. Intracisternal butyrate significantly improved survival period in septic rats. These results suggest that butyrate acts in the central nervous system to improve gut permeability and visceral nociception through cannabinoid signaling. Endogenous orexin in the brain may mediate the reduction of intestinal hyperpermeability by central butyrate through the vagus nerve. We would suggest that improvement of leaky gut by central butyrate may induce visceral antinociception and protection from septic lethality.

Microecological treatment of hyperuricemia using Lactobacillus from pickles

BackgroundHyperuricemia is one of the important risk factors for gout, arteriosclerosis, cardiovascular and cerebrovascular disease. Lactobacillus has attracted much attention due to its role in the regulation of intestinal function and tumor resistance, but its ability to reduce uric acid is unclear. Pickles are a traditional fermented food rich in lactic acid bacteria (LAB).ResultsLAB strains were isolated from 18 pickles and their tolerance to acid bile salts, trypsin, pepsin were evaluated after screening by nucleoside degradation. 16S rDNA sequence analysis was used to identify LAB strains. Furthermore, we established rat model of hyperuricemia and demonstrated that Lactobacillus could alleviate hyperuricemia and reduce kidney injury.ConclusionThis study suggests that microecological treatment with Lactobacillus represents a feasible option for patients with chronic hyperuricemia.

Short-chain fatty acids augment rat duodenal mucosal barrier function.

What is the central question of this study? Small intestinal epithelium is exposed to high concentrations of short-chain fatty acids (SCFAs), but their role in regulating intestinal mucosal barrier function and motility is not fully understood. What is the main finding and its importance? By perfusing the duodenal segment in anaesthetized rats, we show that acetate and propionate significantly decrease mucosal paracellular permeability and transepithelial net fluid flux and increase mucosal bicarbonate secretion. Likewise, SCFAs administered i.v. decrease mucosal permeability but decrease bicarbonate secretion. Altered luminal chemosensing or aberrant signalling in response to SCFAs might contribute to symptoms observed in patients with suppressed mucosal barrier function. Short-chain fatty acids (SCFAs) are produced by bacterial fermentation in the large intestine, particularly from diets containing fibres and carbohydrates. The small intestinal epithelium is exposed to SCFAs derived mainly from oral bacteria or food supplementation. Although luminal nutrients are important in regulation of intestinal functions, the role of SCFAs in regulation of small intestinal mucosal barrier function and motility has not been fully described. The aim of the present study was to elucidate the effects of acetate and propionate on duodenal mucosal barrier function and motility. Rats were anaesthetized with thiobarbiturate, and a 30mm segment of proximal duodenum with an intact blood supply was perfused. The effects on duodenal bicarbonate secretion, blood-to-lumen clearance of 51 Cr-EDTA, motility and transepithelial net fluid flux were investigated. Perfusion of the duodenum with acetate or propionate significantly decreased mucosal paracellular permeability and transepithelial net fluid flux and significantly increased bicarbonate secretion. Acetate or propionate administered as an i.v. infusion decreased the mucosal paracellular permeability, but significantly decreased bicarbonate secretion. Luminal SCFAs changed the duodenal motility pattern from migrating motor complexes to fed patterns. Systemic administration of glucagon-like peptide-2 induced increases in both bicarbonate secretion and net fluid absorption, but did not change motility. Glucagon-like peptide-2 infusion during luminal perfusion of SCFAs significantly reduced the motility. In conclusion, SCFAs decreased duodenal paracellular permeability and net fluid flux. Short-chain fatty acids induced opposite effects on bicarbonate secretion after luminal and i.v. administration. Presence of SCFAs in the lumen induces fed motility patterns. Altered luminal chemosensing and aberrant signalling in response to SCFAs might contribute to symptoms observed in patients with suppressed barrier function.

Roles of Biogenic Amines in Intestinal Signaling.

Biogenic amines in the gastrointestinal tract are important metabolites of dietary protein and amino acids with the help of gut digestive enzymes and microbes, which play a crucial role in the regulation of intestinal functions, including digestion, absorption, and local immunity. However, high concentrations of biogenic amines can induce adverse reactions and are harmful to animal's health. Therefore, it is crucial to have a clear understanding of how different biogenic amines interact with a body's intestinal function signaling pathways and to monitor the content of biogenic amines in the gastrointestinal tract. And in turn, the proper concentration of dietary protein and balanced amino acids for humans and livestock could be given. Though numerous methods have been developed and improved for the detection of biogenic amines in foods or wines much less attention has been paid directly to the determination of amine levels in the gastrointestinal tract. In this article, we mainly focus on the interaction of amines with the intestinal function signaling pathway and the broad impacts on animal physiology, and our modified method to accurately and quickly detect the biogenic amines in the digesta of an animal intestine.

THE SIGNIFICANCE OF BREASTFEEDING FOR THE INFANT GROWTH AND DEVELOPMENT: A REVIEW

Based on the literature, the review shows the real value of breast milk as the most optimal type of postnatal feeding of infants. We describe biological mechanisms that are supposed to mediate the influence of breastfeeding on maturation of immune response, regulation of intestinal functions, trophic effect on small and large intestinal mucosa, its microflora and somatic growth of an infant. In infancy, the protective properties of breast milk against intestinal infections are largely related to its prebiotic effect. According to the results of the studies on the structure of the milk fat mycella envelope, their protein not only participate in bacterial adhesion, but also exert substantial anti-microbial activity due to presence of antimicrobial components. We discuss the role of protective nutrients, such as zinc, iron, iodine, selenium and vitamin A and review the results of studies performed in various countries and aimed at evaluation of an association between the type of feeding of an infant in the 1 year of life and the risk of development of somatic abnormalities. A strong influence of micronutrient deficiencies in the pregnant and breastfeeding woman on delay of in utero development has been shown, as well as its contribution to formation of congenital ab- st normalities of any organ or system, connective tissue dysplasia, initiation and development of alimentary-related conditions in infants.

Effect of continuous ingestion of a beverage prepared with Lactobacillus gasseri CP2305 inactivated by heat treatment on the regulation of intestinal function

Commercialized products containing live lactic acid bacteria (LAB) are available for the purpose of modifying gastrointestinal function. In contrast, the impact of sterilized LAB, especially rod-shaped LAB, on intestinal regulation is not fully understood. Here, we examined the beneficial effects of sterilized Lactobacillus gasseri CP2305 (CP2305) as a “paraprobiotic” on gastrointestinal function in a double-blind, placebo-controlled trial. Subjects (n=39) were healthy individuals who had a tendency toward constipation (n=20) or frequent bowel movements (n=19). They included both genders (15 males and 24 females) and were 20–70years of age (mean 44.4±12.4years). Subjects with constipation or frequent bowel movements were randomly divided into two groups, and they ingested either an artificially acidified milk-based placebo beverage or a heat-inactivated CP2305 fermented milk (FM)-based beverage for 3weeks. Subjects kept a stool diary to record the frequency of bowel movements, the feeling after defecation and the fecal conditions. Fresh fecal samples were collected to evaluate the fecal characteristics and to analyze the fecal metabolites and the composition of intestinal microbiota. The stool characteristics, including the subjective and objective Bristol stool scale scores, output, and color tone, were improved in the heat-inactivated CP2305 FM-based beverage group (CP2305 group), especially in subjects who had a tendency toward constipation. Analyses of the fecal samples showed that the concentrations of short-chain fatty acids (SCFAs) were significantly increased in the CP2305 group. The population of Clostridium cluster IV was significantly increased in the CP2305 group. The heat-inactivated CP2305 FM had a beneficial effect on the regulation of intestinal function. Improvement was observed chiefly in subjects that had a tendency toward constipation. These results suggest that heat-inactivated CP2305 functions as a “paraprobiotic”.

Up-regulation of intestinal type 1 taste receptor 3 and sodium glucose luminal transporter-1 expression and increased sucrose intake in mice lacking gut microbiota

The chemosensory components shared by both lingual and intestinal epithelium play a critical role in food consumption and the regulation of intestinal functions. In addition to nutrient signals, other luminal contents, including micro-organisms, are important in signalling across the gastrointestinal mucosa and initiating changes in digestive functions. A potential role of gut microbiota in influencing food intake, energy homeostasis and weight gain has been suggested. However, whether gut microbiota modulates the expression of nutrient-responsive receptors and transporters, leading to altered food consumption, is unknown. Thus, we examined the preference for nutritive (sucrose) and non-nutritive (saccharin) sweet solutions in germ-free (GF, C57BL/6J) mice compared with conventional (CV, C57BL/6J) control mice using a two-bottle preference test. Then, we quantified mRNA and protein expression of the sweet signalling protein type 1 taste receptor 3 (T1R3) and α-gustducin and Na glucose luminal transporter-1 (SGLT-1) of the intestinal epithelium of both CV and GF mice. Additionally, we measured gene expression of T1R2, T1R3 and α-gustducin in the lingual epithelium. We found that, while the preference for sucrose was similar between the groups, GF mice consumed more of the high concentration (8%) of sucrose solution than CV mice. There was no difference in either the intake of or the preference for saccharin. GF mice expressed significantly more T1R3 and SGLT-1 mRNA and protein in the intestinal epithelium compared with CV mice; however, lingual taste receptor mRNA expression was similar between the groups. We conclude that the absence of intestinal microbiota alters the expression of sweet taste receptors and GLUT in the proximal small intestine, which is associated with increased consumption of nutritive sweet solutions.

Regulation of intestinal phosphate cotransporter NaPi IIb by ubiquitin ligase Nedd4-2 and by serum- and glucocorticoid-dependent kinase 1.

Serum and glucocorticoid-inducible kinase 1 (SGK1) is highly expressed in enterocytes. The significance of the kinase in regulation of intestinal function has, however, remained elusive. In Xenopus laevis oocytes, SGK1 stimulates the epithelial Na(+) channel by phosphorylating the ubiquitin ligase Nedd4-2, which regulates channels by ubiquitination leading to subsequent degradation of the channel protein. Thus the present study has been performed to explore whether SGK1 regulates transport systems expressed in intestinal epithelial cells, specifically type IIb sodium-phosphate (Na(+)-P(i)) cotransporter (NaPi IIb). Immunohistochemistry in human small intestine revealed SGK1 colocalization with Nedd4-2 in villus enterocytes. For functional analysis cRNA encoding NaPi IIb, the SGK isoforms and/or the Nedd4-2 were injected into X. laevis oocytes, and transport activity was quantified as the substrate-induced current (I(P)). Exposure to 3 mM phosphate induces an I(P) in NaPi IIb-expressing oocytes. Coinjection of Nedd4-2, but not the catalytically inactive mutant (C938S)Nedd4-2, significantly downregulates I(P), whereas the coinjection of (S422D)SGK1 markedly stimulates I(P) and even fully reverses the effect of Nedd4-2 on I(P). The effect of (S422D)SGK1 on NaPi IIb is mimicked by wild-type SGK3 but not by wild-type SGK2, constitutively active (T308D,S473D)PKB, or inactive (K127N)SGK1. Moreover, (S422D)SGK1 and SGK3 phosphorylate Nedd4-2. In conclusion, SGK1 stimulates the NaPi IIb, at least in part, by phosphorylating and thereby inhibiting Nedd4-2 binding to its target. Thus the present study reveals a novel signaling pathway in the regulation of intestinal phosphate transport, which may be important for regulation of phosphate balance.

Probiotics in gastroenterology

Probiotics are defined as live microorganisms of human origin. Their use may favorably influence human health and ameliorate or prevent certain diseases. Prebiotics are non-digestible foodstuffs (fiber, oligofructans - "colonic foods"), which enter the colon and are metabolized by the probiotics. Probiotics should fulfill the following criteria: Phenotypic and genotypic classification, no pathogenic properties, human origin, application in the living state, resistance to gastric acid and bile, ability to adhere to colonocytes, ability to colonize the gut, clinically proved favorable health-effect, and safety. Experimental and clinical studies supplied evidence of the possible use of probiotics in the following diseases: Traveler's diarrhea, antibiotic-associated diarrhea, relapsing Clostridium difficile colitis, infantile diarrhea, rotavirus enteritis, inflammatory bowel disease, irritable bowel syndrome, colon cancer, peritonitis, acute pancreatitis, and diarrhea associated with HIV infection. Probiotics displayed the following effects in these studies: Involvement in production of essential nutrients of the colonic mucosa, beneficial effect on intestinal immunity, recovery of the disturbed gut mucosal barrier and prevention of microbial translocation, elimination of toxins and eradication of microbial pathogens, production of steroids from cholesterol and reduction of its pool in circulation, participation in regulation of intestinal functions, reduced incidence of chemically induced colon tumors in rodents. Probiotics open new therapeutic modalities in a number of diseases and it may be expected that their importance will increase with growing knowledge and experience.

Upregulation of Reg 1α and GW112 in the epithelium of inflamed colonic mucosa

BACKGROUND AND AIMSColonic epithelium is involved in the regulation of intestinal function and mucosal immune responses, and its function is altered in inflammatory bowel disease (IBD). However, a comprehensive analysis...

Glycosphingolipid (GSL) microdomains as attachment platforms for host pathogens and their toxins on intestinal epithelial cells: activation of signal transduction pathways and perturbations of intestinal absorption and secretion.

Glycosphingolipid (GSL)-enriched microdomains are used as cellular binding sites for various pathogens including viruses and bacteria. These attachment platforms are specifically associated with transducer molecules, so that the binding of host pathogens (or their toxins) to the cell surface may result in the activation of signal transduction pathways. In the intestinal epithelium, such pathogen-induced dysregulations of signal transduction can elicit a severe impairment of enterocytic functions. In this study, we demonstrate that the interaction of a bacterial toxin (cholera toxin) and a viral envelope glycoprotein (HIV-1 gp120) with the apical plasma membrane of intestinal cells is mediated by GSL-enriched microdomains that are associated with G regulatory proteins. These microbial proteins induce a GSL-dependent increase of intestinal fluid secretion by two mechanisms: activation of chloride secretion and inhibition of Na+ -dependent glucose absorption. Taken together, these data support the view that GSL-enriched microdomains in the apical plasma membrane of enterocytes are involved in the regulation of intestinal functions.

Modulation of Barrier Function of Small Intestinal Epithelial Cells by Lamina Propria Fibroblasts in Response to Lipopolysaccharide: Possible Role of TNFα in Inducing Barrier Dysfunction

Recent evidence suggests an interaction between immune, enteric neural and fibroblasts in the regulation of intestinal function. Earlier, we have reported that lipopolysaccharide (LPS) induced cell proliferation, collagen synthesis and production of proinflammatory mediators in lamina propria fibroblasts. In this report, we investigated the change in transepithelial resistance (TER) as a marker of epithelial barrier function by lipopolysaccharide (LPS) and its modulation by human small intestinal lamina propria fibroblasts (HSILPF). Epithelial cells incubated with LPS alone did not show any change in the TER at any concentration or prolonged exposure. However, co-cultivation of epithelial cells with lamina propria fibroblasts which had been exposed to LPS resulted in a rapid decrease in TER by 2 hr. The decrease in the TER was continued till 8 hr followed by returning to the basal level by 24 hr. The supernatant of LPS-treated HSILPF was less effective in causing a fall in the TER than HSILPF itself. The fall in TER was accompanied by loosening of tight junctions as depicted by increased penetration of horse radish peroxidase (HRP) across the epithelial cells from the apical to the basal side. Increased incorporation of 3[H]thymidine (tritiated thymidine) in epithelial cells was observed at 48 hr in the presence of LPS-treated HSILPF. The decrease in TER during the early time period in epithelial cells was abrogated to 70% by incubating the LPS-treated HSILPF and the conditioned medium of LPS-treated HSILPF with anti-TNFalpha antibody, and not with antibody to other cytokines like IL1alpha, IL1beta, IL6 and IL8. Overall, these results suggest that TNFalpha produced by HSILPF in response to LPS as a soluble form cause a decrease in the TER and loosening of tight junctions, and such early changes in the epithelial barrier may contribute to local inflammation in the gut.