Intestinal Mucosal Atrophy Research Articles

Helicobacter pylori surveillance study in the Eastern Anatolia Region; single center

Aim: The prevalence of Helicobacter pylori (H. pylori) varies among populations as well as among the world's populations. In this study, we aimed to investigate the frequency and effects of H. pylori in our patients living in the Eastern Anatolia Region. Materials and methods: This retrospective study was conducted with 2062 patients living in the Eastern Anatolia Region between 2021-2022 and applying to the endoscopy unit for gastroscopy. The demographic characteristics, gastroscopy findings, and histopathological characteristics of the materials taken during the endoscopy of our patients who applied to us for various indications were recorded in the hospital database. Results: The average age of the patients included in our study was 45.9±16.4 years. 1100 of these patients were women and 962 were men. 308 of the patients had gastric mucosal atrophy, 224 had intestinal metaplasia, and 1151 were H. pylori positive. Of the H. pylori-positive patients, 214 had bulbar ulcers and 48 had stomach ulcers. Intestinal metaplasia and gastric mucosal atrophy were statistically significantly associated with the age of the patients. Conclusion: H. pylori infection causes many changes in the stomach, both endoscopically and histopathologically. However, the main reason for this change is host genetics and the virulence of H. pylori.

Curcumin promotes renewal of intestinal epithelium by miR-195-3p

Ethnopharmacological relevanceTurmeric (Curcuma longa) has been used to treat gastrointestinal disorders in the Indian Ayurvedic medical system. According to the theory behind traditional Chinese medicine, turmeric can be distributed in the spleen meridian, for which it has been used as a digestive aid. Curcumin (Cur), a natural polyphenol compound originally derived from turmeric, has anti-inflammatory activity and can assist in treating inflammatory bowel disease. Aims of the studyTo investigate curcumin's protective effects on intestinal epithelium and explore the underlying miR-195-3p-related mechanisms. Materials and methodsThe miR-195-3p mimics were used to over-express miR-195-3p. The in vitro effects of Cur and miR-195-3p on the intestine were shown utilizing intestinal cryptlike epithelial cell line-6 (IEC-6) cells. By fasting for 48 h, an intestinal mucosal atrophy model of SD rats was created in vivo. Cur (25 or 50 mg/kg) was assessed for its protective effect on intestinal epithelium. Glycyrrhetinic acid (GA) with an intestinal protective effect reported in our previous research was adopted as a positive drug for the in vivo and in vitro bioactivity evaluation since there is no universally positive drug for either intestinal mucosal restitution or miR-195-3p modulation. ResultsCur protects the intestinal epithelium and promotes its repair after injury via down-regulating miR-195-3p. In vitro experiments showed that Cur inhibited the apoptosis of IEC-6 cells, stimulated their growth, and down-regulated the level of miR-195-3p in cells. When miR-195-3p was overexpressed, the viability of IEC-6 cells decreased while the apoptosis rate increased. All the above detrimental effects were alleviated after curcumin intervention. Moreover, Cur reversed the effect of miR-195-3p on its downstream occludin. In vivo, results showed that 48-h fasting impaired the integrity of the small intestinal mucosa (abnormal crypt structure and reduced goblet cell number), which was ameliorated by Cur treatment. In addition, the Cur treatment reversed both the increased expression level of miR-195-3p and decreased levels of ki-67 and occludin caused by fasting. ConclusionsCur could promote the proliferation and repair after injury of the intestinal mucosa by down-regulating miR-195-3p.

Control of Paneth cell function by HuR regulates gut mucosal growth by altering stem cell activity.

Rapid self-renewal of the intestinal epithelium requires the activity of intestinal stem cells (ISCs) that are intermingled with Paneth cells (PCs) at the crypt base. PCs provide multiple secreted and surface-bound niche signals and play an important role in the regulation of ISC proliferation. Here, we show that control of PC function by RNA-binding protein HuR via mitochondria affects intestinal mucosal growth by altering ISC activity. Targeted deletion of HuR in mice disrupted PC gene expression profiles, reduced PC-derived niche factors, and impaired ISC function, leading to inhibited renewal of the intestinal epithelium. Human intestinal mucosa from patients with critical surgical disorders exhibited decreased levels of tissue HuR and PC/ISC niche dysfunction, along with disrupted mucosal growth. HuR deletion led to mitochondrial impairment by decreasing the levels of several mitochondrial-associated proteins including prohibitin 1 (PHB1) in the intestinal epithelium, whereas HuR enhanced PHB1 expression by preventing microRNA-195 binding to the Phb1 mRNA. These results indicate that HuR is essential for maintaining the integrity of the PC/ISC niche and highlight a novel role for a defective PC/ISC niche in the pathogenesis of intestinal mucosa atrophy.

Licochalcone A promotes renewal of intestinal mucosa through modulating uc.173

Ethnopharmacological relevanceLicorice can nourish Pi (spleen) and thereby strengthening the digestive system according to the theory of traditional Chinese medicine. Licorice has been generally used in the compound prescription to treat intestinal inflammatory disease. Licochalcone A (Lico A) is one of the characteristic molecules from licorice. T-UCRs, which are transcribed from ultraconserved regions, are a new class of long noncoding RNAs related to the renewal of intestinal epithelial renewal. Aim of the studyThis study aimed to investigate the effect and the uc.173-related mechanism of Lico A on intestinal epithelial renewal. Materials and methodsIE-6 and Caco-2 cells were used to evaluate the effect of Lico A on apoptosis, proliferation, and migration of IECs. The intestinal organoid was used to investigate ex vivo effect and mechanism of Lico A promoting intestinal organoid development. C57BL/6J mice (both normal and uc.173-deficient ones) were used to examine the in vivo effect of Lico A on the renewal of intestinal mucosa. ResultsThe expression of three T-UCRs related to the intestinal mucosa renewal was altered in Lico A-treated IECs. Lico A promoted the proliferation and inhibited the apoptosis of IECs through uc.173/miR-195 pathway. The development of intestinal organoids and the renewal of intestinal mucosa of mice subjected to the 48-h FAST were all promoted by the treatment of Lico A. Moreover, the growth arrest of uc.173-deficient intestinal organoids and the atrophy of intestinal mucosa in uc.173-deficient mice could be rescued by the Lico A administration. ConclusionResults in this paper suggest that targeting T-UCRs may be the novel therapeutic approach for the promotion of epithelial regeneration, and through stimulating the regeneration of intestinal mucosa, Lico A may become a new therapeutic agent for the maintenance of intestinal epithelial integrity.

CHALLENGES IN DIFFERENTIAL DIAGNOSIS OF COELIAC DISEASE AND GLUTEN INTOLERANCE IN CHILDREN

CHALLENGES IN DIFFERENTIAL DIAGNOSIS OF COELIAC DISEASE AND GLUTEN INTOLERANCE IN CHILDREN

Serum zinc levels in cancer patients are low and difficult to elevate when complicated by liver cirrhosis: A retrospective study.

In this study, we analyzed blood zinc concentration in patients with various cancer types and the degree of improvement in relation to the underlying disease following treatment with zinc preparations. Serum zinc levels of 530 cancer patients whose blood zinc levels were measured at our hospital from 2016 to 2021 were retrospectively examined in accordance with the primary disease. Changes in zinc levels were analyzed in 155 patients whose zinc levels had been measured on 2 or more occasions in accordance with whether they had received zinc preparations. In addition, the concentration course of zinc before and after zinc formulation administration in 73 patients was examined in accordance with the presence or absence of liver cirrhosis complications. Mean serum zinc levels were below normal in all carcinomas measured, and zinc levels were significantly lower in cirrhosis-hepatocarcinoma cases than in other primary disease cases. Furthermore, serum zinc levels in patients who did not receive zinc preparations decreased significantly over time. In patients who received zinc preparations, the elevated levels of zinc after treatment were significantly lower in patients with cirrhosis than in those without cirrhosis. There was a weak inverse correlation between pre-dose zinc concentration and increased zinc concentration in patients with cirrhosis. In the analysis of covariance, the presence of liver cirrhosis was predominantly correlated with elevated zinc per dose. In summary, serum zinc levels in cancer patients are low and especially low in cancer patients with liver cirrhosis compared with those without cirrhosis after the administration of zinc preparations.

OA20 Pneumatosis intestinalis with spontaneous pneumoperitoneum in a patient with systemic sclerosis-myositis overlap syndrome: a case report and review of the literature

OA20 Pneumatosis intestinalis with spontaneous pneumoperitoneum in a patient with systemic sclerosis-myositis overlap syndrome: a case report and review of the literature

Gut-Barrier Disruption After Laparoscopic Versus Open Major Liver Resection in the Rat

BackgroundMajor liver resection may compromise gut-barrier function, increasing the risk of postoperative infectious complications. The aim of the present experimental study was to compare the effect of the laparoscopic versus the open technique for major liver resection on integrity as well as inflammatory and immune responses of the gut barrier. MethodsWistar rats were subjected to open 70% hepatectomy (group H), laparoscopic 70% hepatectomy (group LH), sham operation (group S) or no intervention (group C). At various timepoints (1 hour–1 week) after operation, ileal tissue was excised for oxidative state assessment (TBARS levels), histopathologic examination, histomorphometric analysis, immunohistochemical assessment of the mitotic and apoptotic activity, and tissue expression of inflammatory (interleukin-6, tumor necrosis factor-α, nuclear factor-κB and vascular cell adhesion molecule-1) and immune response biomarkers (CD4+ and CD8+ T-lymphocytes) of the intestinal mucosa. ResultsNo changes were noted in oxidative state. The histopathologic profile was less deteriorated in group LH compared to group H. Intestinal mucosa atrophy was less intense in group LH compared to group H and was related to an equally compromised crypt cell mitotic activity. Tissue overexpression of interleukin-6, tumor necrosis factor-α, nuclear factor-κΒ, vascular cell adhesion molecule-1, CD4+, and CD8+ T-lymphocytes was less pronounced in group LH compared to group H. ConclusionThe employment of the laparoscopic technique for major liver resection in the rat attenuated disruption of the gut barrier compared to the open procedure. This was related to less pronounced inflammatory and immune responses of the intestinal mucosa.

The protective effects of hepatocyte growth factor on the intestinal mucosal atrophy induced by total parenteral nutrition in a rat model

PurposeTotal parental nutrition (TPN) causes gastrointestinal mucosal atrophy. The present study investigated the effects of hepatocyte growth factor (HGF) on the intestinal mucosal atrophy induced by TPN.MethodsRats underwent jugular vein catheterization and were divided into four groups: oral feeding (OF), TPN alone (TPN), TPN plus low-dose HGF (0.3 mg/kg/day; TPNLH), and TPN plus high-dose HGF (1.0 mg/kg/day; TPNHH). On day 7, rats were euthanized, and the small intestine was harvested and evaluated histologically. The expression of c-MET, a receptor of HGF, and nutrition transporter protein were evaluated using quantitative polymerase chain reaction.ResultsThe jejunal villus height (VH) and absorptive mucosal surface area in the TPNHH group were significantly higher than in the TPN group (p < 0.05). The VH in the ileum showed the same trend only in the TPNHH group, albeit without statistical significance. The crypt cell proliferation rate (CCPR) of the jejunum in both HGF-treated groups was significantly higher than in the TPN group (p < 0.01). The expression of c-MET and transporter protein in all TPN-treated groups was decreased compared with that in the OF group.ConclusionHGF attenuated TPN-associated intestinal mucosal atrophy by increasing the villus height, which was associated with an increase in CCPR.

Changes in the microstructure of the small intestine of sheep infected naturally with Paramphistomum cervi after treatment with Antitrem

It is clear that the chemical structure of a drug and its process, which are the determinants of the degree of activity an anthelmintic have on the organs and tissues of trematodes, as well as their hosts. This study demonstrates changes in the microstructure of the small intestine of sheep with impulsive Paramphistomiasis after treatment with Antitrem. Seven days after giving “Antitrem (contain oxyclosanide and pyrantela pamoate, OLKAR Release, Russia)” at a dose of 200 mg/kg once perorally, fixed in 70% alcohol and administered according to generally accepted histological methods, the small intestine of the sheep which it was administered to was impulsively attacked by Paramphistomum cervi. Partial atrophy of intestinal mucosa, common dystrophic changes in the epithelium, and destruction of individual goblet cells represented the microstructural changes in the small intestine of infected sheep with Paramphistomum cervi after treatment with Antitrem. Microstructural changes in the small intestine of the sheep are composed of proliferative procedures, a reduction in the content of carbohydrate compounds, and a change in the protein component in the tissues of the organ and stagnation of the secretory product in the cells.

Extracellular vesicles isolated from milk can improve gut barrier dysfunction induced by malnutrition

Malnutrition impacts approximately 50 million children worldwide and is linked to 45% of global mortality in children below the age of five. Severe acute malnutrition (SAM) is associated with intestinal barrier breakdown and epithelial atrophy. Extracellular vesicles including exosomes (EVs; 30–150 nm) can travel to distant target cells through biofluids including milk. Since milk-derived EVs are known to induce intestinal stem cell proliferation, this study aimed to examine their potential efficacy in improving malnutrition-induced atrophy of intestinal mucosa and barrier dysfunction. Mice were fed either a control (18%) or a low protein (1%) diet for 14 days to induce malnutrition. From day 10 to 14, they received either bovine milk EVs or control gavage and were sacrificed on day 15, 4 h after a Fluorescein Isothiocyanate (FITC) dose. Tissue and blood were collected for histological and epithelial barrier function analyses. Mice fed low protein diet developed intestinal villus atrophy and barrier dysfunction. Despite continued low protein diet feeding, milk EV treatment improved intestinal permeability, intestinal architecture and cellular proliferation. Our results suggest that EVs enriched from milk should be further explored as a valuable adjuvant therapy to standard clinical management of malnourished children with high risk of morbidity and mortality.

The Farnesoid X Receptor Agonist Tropifexor Prevents Liver Damage in Parenteral Nutrition-fed Neonatal Piglets.

Intestinal failure-associated liver disease (IFALD) is a life-threatening complication for patients with intestinal failure who receive long-term parenteral nutrition (PN). We evaluated the effects of the farnesoid X receptor agonist tropifexor on a neonatal piglet model of IFALD fed with PN. The piglets received PN and tropifexor for 14 days, then levels of liver enzymes, bile acid metabolism, inflammation, and intestinal barrier markers were assessed using quantitative real-time PCR. Fibroblast growth factor (FGF) 19 serum levels were determined using enzyme-linked immunosorbent assays. Bile acids were determined in liver, serum, and intestinal contents, and the microbiome was sequenced in different intestinal segments. The PN model was established in newborn piglets. The levels of serum liver enzymes, pro-inflammatory factors, and oxidative stress increased in the livers of piglets fed with PN, but not in those fed with PN and tropifexor. Tropifexor stimulated FGF19 expression in ileal epithelial cells, increased portal FGF19 levels, then inhibited cholesterol 7α-hydroxylase expression in the liver. Tropifexor increased the relative abundance of bacteria associated with bile salt hydrolase and 7α-dehydrogenation in the contents of ileum and altered the composition of bile acids in serum, liver, and intestinal contents. Tropifexor also inhibited intestinal inflammation, alleviated intestinal mucosal atrophy, and improved the intestinal barrier. Tropifexor might prevent liver damage in neonatal piglets receiving PN by altering the composition of intestinal microbiota and bile acids. Tropifexor also alleviates intestinal inflammation and preserves the intestinal barrier.

Safra reflüsü bulunan ve bulunmayan gastrit hastalarında gastrik mukozal atrofi, intestinal metaplazi ve Helicobacter pylori durumu: Safra iyi mi kötü mü?

Background and Aims: To investigate the relation between bile reflux and gastric mucosal atrophy, intestinal metaplasia, and Helicobacter pylori status in patients with gastritis. Materials and Methods: A total of 217 patients (mean ± SD; age: 33.2±7.9 years; 51.2% males) with gastritis were divided into two groups: patients with intragastric bile reflux (n = 134; confirmed by pathology in 20 patients) and without bile reflux (control group; n = 83). The status of Helicobacter pylori and presence of intestinal metaplasia and gastric atrophy were evaluated with respect to the presence of bile reflux. Results: A positive Helicobacter pylori status, intestinal metaplasia, and gastric atrophy were observed in 85 (39.2%), 72 (33.2%), and 66 (30.4%) patients, respectively. No significant difference was noted between patients with gastritis with or without bile reflux in terms of a positive Helicobacter pylori status (38.8% vs. 45.8%), intestinal metaplasia (32.8% vs. 33.7%), and gastric atrophy (30.6% vs. 30.1%). However, the pathological confirmation of bile reflux gastritis was associated with a significantly lower rate of Helicobacter pylori positivity (0.0% vs. 45.6%; p = 0.001), intestinal metaplasia (5.0% vs. 37.7%; p = 0.009), and gastric atrophy (0.0% vs. 36.0%; p = 0.003). In patients with bile reflux (n = 134), the intestinal metaplasia and gastric mucosal atrophy rates were similar with respect to the H. pylori status. Conclusion: The rates of Helicobacter pylori positivity, intestinal metaplasia, and gastric atrophy were similar in patients with gastritis with or without bile reflux. However, the frequency of Helicobacter pylori, intestinal metaplasia, and gastric mucosal atrophy was lower in patients with pathologically confirmed biliary gastritis.

Fecal Microbiota Transplantation and Hydrocortisone Ameliorate Intestinal Barrier Dysfunction and Improve Survival in a Rat Model of Cecal Ligation and Puncture-Induced Sepsis.

Sepsis is a life-threatening syndrome which can progress to multiple organ dysfunction with high mortality. Intestinal barrier failure exerts a central role in the pathophysiological sequence of events that lead from sepsis to multiple organ dysfunction. The present study investigated the role of hydrocortisone (HC) administration and fecal microbiota transplantation (FMT) in several parameters of the gut barrier integrity, immune activation, and survival, in a model of polymicrobial sepsis in rats. Forty adults male Wistar rats were randomly divided into four groups: sham (group I), cecal ligation and puncture (CLP) (group II), CLP + HC (2.8 mg/kg, intraperitoneally single dose at 6 h) (group III), and CLP + FMT at 6 h (group IV). At 24 h post-CLP, ileal tissues were harvested for histological and immunohistochemical analyses while endotoxin, IL-6, and IL-10 levels in systemic circulation were determined. In a second experiment the same groups were observed for 7 days for mortality, with daily administration of hydrocortisone (group III) and FMT (group IV) in surviving rats. HC administration and FMT significantly reduced mortality of septic rats by 50%. These interventions totally reversed intestinal mucosal atrophy by increasing villous density and mucosal thickness (μm, mean ± SD: Group I: 620 ± 35, Group II: 411 ± 52, Group III: 622 ± 19, Group IV: 617 ± 44). HC and FMT reduced the apoptotic body count in intestinal crypts whereas these increased the mitotic/apoptotic index. Activated caspase-3 expression in intestinal crypts was significantly reduced by HC or FMT (activated caspase-3 (+) enterocytes/10 crypts, mean ± SD: Group I: 1.6 ± 0.5, Group II: 5.8 ± 2.4, Group III: 3.6 ± 0.9, Group IV: 2.3 ± 0.6). Both treatments increased Paneth cell count and decreased intraepithelial CD3(+) T lymphocytes and inflammatory infiltration of lamina propria to control levels. In the sham group almost the total of intestinal epithelial cells expressed occludin (92 ± 8%) and claudin-1 (98 ± 4%) and CLP reduced this expression to 34 ± 12% for occludin and 35 ± 7% for claudin-1. Administration of HC significantly increased occludin (51 ± 17%) and claudin-1 (77 ± 9%) expression. FMT exerted also a significant restoring effect in tight junction by increasing occludin (56 ± 15%) and claudin-1 (84 ± 7%) expression. The beneficial effects of these treatments on gut barrier function led to significant reduction of systemic endotoxemia (EU/mL, mean ± SD: Group I: 0.93 ± 0.36, Group II: 2.14 ± 1.74, Group III: 1.48 ± 0.53, Group IV: 1.61 ± 0.58), while FMT additionally decreased IL-6 and IL-10 levels. Fecal microbiota transplantation and stress dose hydrocortisone administration in septic rats induce a multifactorial improvement of the gut mechanical and immunological barriers, preventing endotoxemia and leading to improved survival.

Evaluation of upper endoscopic findings in patients with restless legs syndrome and gastric complaints.

The effect of gastrointestinal system disorders on Restless Legs Syndrome/Willis-Ekbom disease (RLS/WED) has been previously demonstrated by using serological tests. However, this association has not been supported by histopathological studies so far. To investigate the relationship between RLS/WED, upper endoscopic imaging and histopathological results in patients diagnosed with RLS who underwent endoscopy because of gastrointestinal system (GIS) complaints. Case-control study, including 100 patients diagnosed with RLS who presented dyspeptic complaints and underwent upper GIS endoscopy and 106 age- and sex-matched controls. RLS diagnosis was evaluated according to the four main diagnostic criteria determined by the International RLS Study Group. All patients underwent upper GIS endoscopic intervention and at least one gastric and/or antral biopsy. There was no significant difference between patients and controls in relation to endoscopically seen gastric ulcer, duodenal ulcer, gastroesophageal reflux disease (GERD) findings and Helicobacter pylori (HP) positivity (p>0.05). Intestinal metaplasia and mucosal atrophy were more common in RLS/WED patients compared to controls (p=0.026 and p=0.017, respectively). Additionally, ferritin levels were found to be lower than the reference value. The detection of increased severity of intestinal metaplasia, mucosal atrophy, and gastric inflammation in RLS/WED patients with dyspeptic complaints may entail the close gastrointestinal system evaluation of these patients. However, larger randomized and controlled trials are required on this subject where patients are evaluated by upper GIS endoscopic biopsy.

Effect of prodigiosin on the alleviation of the intestinal inflammation of weaned rats based on 1H-NMR spectroscopy study and biochemistry indexes

Weaning results in intestinal dysfunction, mucosal atrophy, transient anorexia, and intestinal barrier defects. In this study, the effect of prodigiosin (PG) on the intestinal inflammation of weaned rats was investigated by using 1 H-NMR spectroscopy and biochemistry indexes to regulate the intestinal metabolism. After administration for 14 days, the body mass of the PG group was increased by 1.29‑ and 1.26-fold compared with those of the control and alcohol groups, respectively, using a dose of 200 μg PG·kg-1 body weight per day. PG increased organic acid content and decreased moisture, pH values, and free ammonia in feces. In addition, PG alleviated the intestinal inflammation of weaned rats. The analysis of 1 H-NMR signal peak attribution and the model validation of metabolic data of feces contents showed that PG significantly affected the metabolism of small molecular compounds in the intestinal tract of weaned rats. This study presents the promising alternative of using PG to alleviate intestinal inflammation effectively in the intestinal tract of weaned rats.

Çölyak Hastalığında Glutensiz Diyet Tedavisi: Bir Olgu Sunumu

Çölyak hastalığı, genetik olarak yatkın bireylerde, gluten ve ilişkili proteinlerin tüketimiyle bağırsak mukozasının atrofiye uğramasına neden olan, immün aracılı kronik bağırsak hastalığıdır. Çölyak hastalığının tek tedavisi yaşam boyu katı glutensiz diyet uygulamaktır. Özellikle çocukluk döneminde tanı alan bireylerin, sağlıklı yaşıtları ile benzer büyüme ve gelişme sürecini sürdürebilmesi için diyete uyum şarttır. Glutensiz diyet tedavisinin diyetisyen kontrolünde sıkı bir şekilde takip edilmesi diyete uyumu artırarak kısa sürede serolojik ve klinik bulguların düzelmesini sağlayabilir. Bu yazıda çölyak hastalığı tanısı ile izlenen olguda, glutensiz beslenme tedavisinin önemi ve uygulaması tartışılmıştır.

PO-105 Exercise regulates HMGB1 / TLR4 / NF- κ B pathway by H2S to improve OJ intestinal injury

Objective To study the effect of aerobic exercise on the damage of intestinal mucosal barrier function caused by obstructive jaundice（OJ）and to explore its mechanism of action.&#x0D; Methods 50 male KM mice were randomly divided into 5 groups: sham operation group (S), model group (M), exercise group (TM), DL-Propargylglycine + exercise (PT) group and sodium hydrosulfide + exercise (NT) group.In addition to the S group which are in the common bile duct to the abdominal wall hanging 48 hours to build mouse obstructive jaundice model. In the PT group, PAG (40 mg/kg) was intraperitoneally injected 7 days after surgery; NaHS (50 μmol/kg) was intraperitoneally injected in the NT group 7 days after surgery; TM group, NT group and PT group were graded at 0%, and the speed was 10m/min no weight training (30min/day).After 6 weeks, HE staining was used to observe the morphological changes of the intestinal mucosa.Biochemical analysis was used to detect the concentration of hydrogen sulfide (H2S) in blood and ileum, and total bilirubin (TBIL), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) Liver function, diamine oxidase (DAO), D-lactic acid intestinal barrier function biochemical index; qRT-PCR and immunohistochemical staining were used to observe the expression changes of H2S-mediated related channel mRNA and protein（HMGB1, TLR4 and NF-Kbp6）in intestinal tissues.&#x0D; Results HE staining showed that the intestinal mucosa of group M was atrophied and the villus was broken.Compared with M group, the intestinal mucosa arrangement in TM group was relatively regular. Compared with TM group, intestinal mucosa atrophy in PT group, fluff hair loss, sparseness and disorder, partial mucosa The layer was separated from the lamina propria and the gland was severely damaged. The intestinal mucosa of the NT group was relatively regular, and the changes of intestinal mucosa atrophy were restored. Serum test results showed that H2S levels were higher in the TM group than in the M group; compared with the TM group, the PT group decreased and the NT group increased. DAO level: The TM group was lower than the M group; compared with the TM group, the PT group was elevated and the NT group was decreased. Changes in serum D-lactic acid levels were similar to DAO. The results of qRT-PCR and immunohistochemical staining showed that the expressions of HMGB1, TLR4 and NF-Kbp6 mRNA and protein in the intestinal tissues of mice in TM group were significantly lower than those in M group and PT group, and the mRNA and protein expression levels in NT group were the lowest.&#x0D; Conclusions Aerobic exercise inhibits the HMGB1 / TLR4 / NF-κB signaling pathway through the H2S / CSE system, thereby exerting a protective effect on the intestinal mucosal barrier.

Aryl hydrocarbon receptor/IL-22/Stat3 signaling pathway is involved in the modulation of intestinal mucosa antimicrobial molecules by commensal microbiota in mice.

Compelling evidence demonstrates the crucial role of the commensal microbiota in host physiology and the detrimental effects of its perturbations following antibiotic treatment. However, the effects of commensal microbiota on intestinal mucosa antimicrobial molecules have not been elucidated systematically. Here, we investigate the impacts of antibiotic-induced depletion and subsequent restoration of the intestinal microbiota on the murine antimicrobial molecules in intestinal mucosa. Our results demonstrate that depletion of commensal microbiota leads to intestinal mucosa atrophy and reduction of antimicrobial molecules, including lysozyme, regenerating islet-derived protein 3 gamma (RegIIIγ), and cryptdin 5 mRNA, whereas subsequent reconstitution of intestinal microbiota by fecal microbiota transplantation (FMT) rescues mucosa morphology and antimicrobials. Importantly, our study shows that down-regulation of aryl hydrocarbon receptor (AhR), interleukin-22 (IL-22), and phosphorylated Stat3 (p-Stat3) is associated with decreased antimicrobials, which might mediate the antibiotic-associated intestinal mucosa injury. Last, exogenous activation of the AhR/IL-22/Stat3 signaling pathway with the AhR agonist 6-formylindolo(3,2-b)carbazole (Ficz) rescued antimicrobial molecule levels markedly after antibiotic treatment to levels similar to those following reconstitution of intestinal microbiota by FMT. Together, our results demonstrate that the AhR/IL-22/Stat3 signaling pathway is involved in the modulation of intestinal mucosa antimicrobial molecules by commensal microbiota and suggest this pathway as a promising target in the treatment of antibiotic-associated gut barrier damage.

Glucagon-Like Peptide-2 Improve Intestinal Mucosal Barrier Function in Aged Rats.

Glucagon-like peptide-2 (GLP-2) plays a major role in repairing impaired intestinal mucosa, but its mechanism in the improvement of intestinal barrier function during the aging process remains unclear. In this study, 26-month-old male Sprague-Dawley rats were randomized to control group and GLP-2 group treated with a dose of 250 μg•kg-1•d-1 by intraperitoneal injection. After 14 days of treatment, intestinal mucosal morphometric changes were observed by light microscopy and transmission electron microscopy (TEM). Small intestinal permeability was evaluated by fluorescein isothiocyanate (FITC)-labeled dextran. The mRNA and protein expression of Zonula Occludens-1 (ZO-1), occludin, claudin-1 and the GLP-2 receptor (GLP-2R) were detected by Real-time PCR and Western blot. Our results showed that GLP-2 administration significantly improved the age-related atrophy of intestinal mucosa and villi and increased small intestinal permeability. The mRNA and protein expression of ZO-1and occludin in ileum were up regulated in the GLP-2-treated old rats. In addition, the serum GLP-2 levels were negatively correlated with small intestinal permeability measured by FITC-dextran levels (r=-0.610, P<0.01). Taking all these data together, it is concluded that GLP-2 improved small intestinal epithelial barrier function in aged rats mainly by facilitating intestinal mucosa growth, alleviating the increased small intestinal permeability and increasing ZO-1 and occludin expression. Our observations provide evidence for the clinical significance of GLP-2 in preventing the intestinal epithelial barrier dysfunction during aging.