Stomach Mucus Research Articles

A comprehensive review of oral chitosan drug delivery systems: Applications for oral insulin delivery

Abstract Pharmaceutical scientists have long struggled to develop reliable and efficient systems of administering insulin orally due to multiple barriers, including stomach acidity, enzymatic degradation, and mucus barriers. However, various strategies were developed to avoid insulin degradation in the gastrointestinal tract (GIT) and promote membrane permeability and biological activity. Among these strategies, chitosan polymer-based carriers are widely researched due to their ability to protect insulin in the alimentary canal and deliver it effectively through the intestinal mucosa, improving its bioavailability. To improve chitosan properties, chemical and physical modifications have been developed, and recently, nanoparticles, microparticles, and beads of chitosan exhibited potential systems for oral insulin delivery (OID). This review facilitates an outline of the types of diabetes mellitus, insulin biosynthesis, and gastrointestinal barriers against oral insulin. Moreover, the limitations of subcutaneous insulin delivery and alternative routes of administration are also discussed. As an ideal and most convenient oral administration route, the challenges of safe insulin delivery through the GIT and strategies to elevate its bioavailability are highlighted. In addition, this review focuses on recent advancements in chitosan based carriers for OID and their potential future applications.

Effects of Olea oleaster leaf extract and purified oleuropein on ethanol-induced gastric ulcer in male Wistar rats.

Evaluating the effect of fresh Oleaster leaf extract (OLE) and purified oleuropein (OLR) on ethanol-induced gastric ulcers in rats. HPLC analysis demonstrates the presence of various polyphenol compounds such as ligstroside, luteolin derivative, oleuropein, and comselogoside. Gastric ulcer was induced by administration of ethanol by the gastric gavage route. The olive leaf extract was analyzed by HPLC-PDA-ESI-MS, and OLR was purified. These two compounds were given 2 hr before gastric ulcer induction by ethanol. This study verified that OLE and purified OLR protect from ethanol-induced gastric ulceration and damage, evidenced by the significant decrease in gastric ulcer urea (by 74 and 58% respectively) and stomach mucus content (by 169 and 87% respectively). In addition, the ulcer index (UI) and curative index (CI) levels in the stomach of the rats treated with this supplement were also suppressed by 55 and 46%, respectively. OLE and OLR also decreased the gastric myeloperoxidase (MPO) activity and ameliorated the nitric oxide (NO) content. OLE and OL also ingestion suppressed gastric tumor necrosis factor-alpha (TNF-α) and interleukin (IL-6) rates. Macroscopic and histological findings revealed that OLE and OLR protect from gastric hemorrhage, severe disruption of the gastric mucosa, and neutrophil infiltration. Overall, the findings demonstrate that OLE and OLR have both promising potential with regard to the inhibition of gastric hemorrhage and lesions.

Genetic susceptibility to Helicobacter pylori and the progression of gastrointestinal cancer

The Helicobacter pylori bacteria are spiral-shaped and grow in the stomach's mucus. During its life cycle, H. pylori produces an enzyme called urease that converts urea into ammonia. This enzyme allows the organism to survive a severe, acidic environment by converting urea into ammonia. Molecular genetic studies have identified polymorphisms functional as biomarkers of hereditary predisposition to stomach cancer. Several genes involved in inflammation have been linked to stomach cancer development. Recently, these genes' potential pathogenic and carcinogenic effects have been investigated (APC, CDH1, IL-1, BAX, NOS2, KRAS and MSH2). All these genes' processes have been researched to understand better their potential as biomarkers of gastric carcinogenesis. An in-depth analysis will be required to determine the genetic characteristics of stomach cancer related to H. pylori. It is imperative to research a variety of ethnicities to further use this influence as a critical and fundamental risk factor for stomach illness.

Pomegranate Juice Attenuates Anti-ulcer in Indomethacin-induced Peptic Ulcer

Introduction: Pomegranate (Punica granatum L.) is a well-known fruit that grows in tropical and subtropical areas of the world. In this study, we wanted to find out how pomegranate juice (POMJ) affected rats with gastric ulcers caused by standard drugs. Indomethacin is the most common drug causes gastric ulcer also, most of the NSAID drugs have harmful side effects, so studies have focused on finding an alternative natural solution. Methods: In this study, 25 male albino rats were used and were split into four groups of five rats each. These groups were called control, pomegranate, indomethacin, and standard. The examination took one week to complete. Indomethacin saline suspension (100 mg/kg rat weight) caused gastric ulcers. Pomegranate peel juice (5-10%) reduced stomach ulcer area and ulcer index, gastric juice volume, and acidity. Pomegranate juice restores stomach mucus content and tissue at the histological level. Results: Rats that were given indomethacin and then given pomegranate juice were significantly less likely to get a gastric ulcer. It also lowered the ulcer index to 0.7093±0.36 showing that 52.25 % prevention. Conclusion: The study's macroscopical and microscopical results showed that pomegranate juice might be able to reduce the ulceration caused by indomethacin in a rat model. Pomegranate as a protective food supplement against gastric ulcers.

The Potential Gastro-Protective Effect of Qaysum (Achillea fragrantissima) Against Ethanol-Induced Gastric Ulcer in Wistar Albino Rats.

Gastric ulcer (GU) is among the peak prevalent syndromes. This study investigates the defensive properties of Achillea fragrantissima (Forssk.) Sch.Bip. extract (AFE) against ethanol-induced stomach lesions. Twenty-eight rats were allocated into negative control, positive control, AFE + ethanol, and omeprazole ethanol. In serum and gastric homogenates, oxidative stress displays (e.g., malondialdehyde (MDA), decreased glutathione (GSH), superoxide dismutase enzyme (SOD), and catalase enzyme (CAT)) and inflammatory parameters (e.g., tumor necrosis factor-alpha (TNF-α)) were estimated. GU markers (gastric lesions, ulcer index (UI), pH) were evaluated, and gastric histopathological examinations were performed. The positive control cluster exhibited severe gastric mucosal injuries, reduced stomach mucus secretion, and pH of gastric content. Furthermore, AFE-pretreated rats displayed meaningfully increased periodic acid-Schiff (PAS) countenance in their stomach epithelial layers. Pretreatment with AFE reduced stomach lesions, UI, MDA, and TNF-α levels, while mucus, pH, CAT, GSH, and SOD levels increased. Stomach examination showed significant improvement in gastric mucosa reduced edema and leukocyte infiltration of the submucosal level in pretreatment with the AFE and omeprazole groups versus the ethanol group. Additionally, AFE extracts increase the intensity of the stomach epithelium's PAS. The acute toxicity experiment with an advanced dosage of 5 g/kg AFE did not exhibit any signs of toxicity in the rats. In conclusion, the AFE reduced the effect of ethanol on the gastric mucosa, which may be due to its antioxidants and anti-inflammatory properties.

Mucosal Adhesive Chitosan Nanogel Formulations of Antibiotics and Adjuvants (Terpenoids, Flavonoids, etc.) and Their Potential for the Treatment of Infectious Diseases of the Gastrointestinal Tract.

Bacterial infections are usually found in the stomach and the first part of the small intestine in association with various pathologies, including ulcers, inflammatory diseases, and sometimes cancer. Treatment options may include combinations of antibiotics with proton pump inhibitors and anti-inflammatory drugs. However, all of them have high systemic exposure and, hence, unfavorable side effects, whereas their exposure in stomach mucus, the predominant location of the bacteria, is limited. Chitosan and nanogels based on chitosan presumably are not absorbed from the gastrointestinal tract and are known to adhere to the mucus. Therefore, they can serve as a basis for the local delivery of antibacterial drugs, increasing their exposure at the predominant location of therapeutic targets, thus improving the risk/benefit ratio. We have used E. coli ATCC 25922 (as a screening model of pathogenic bacteria) and Lactobacilli (as a model of a normal microbiome) to study the antibacterial activity of antibacterial drugs entrapped in a chitosan nanogel. Classical antibiotics were studied in a monotherapeutic regimen as well as in combination with individual terpenoids and flavonoids as adjuvants. It has been shown that levofloxacin (LF) in combination with zephirol demonstrate synergistic effects against E. coli (cell viability decreased by about 50%) and, surprisingly, a much weaker effect against Lactobacilli. A number of other combinations of antibiotic + adjuvant were also shown to be effective. Using FTIR and UV spectroscopy, it has been confirmed that chitosan nanogels with the drug are well adsorbed on the mucosal model, providing prolonged release at the target location. Using an ABTS assay, the antioxidant properties of flavonoids and other drugs are shown, which are potentially necessary to minimize the harmful effects of toxins and radicals produced by pathogens. In vivo experiments (on sturgeon fish) showed the effective action of antibacterial formulations developed based on LF in chitosan nanogels for up to 11 days. Thus, chitosan nanogels loaded with a combination of drugs and adjuvants can be considered as a new strategy for the treatment of infectious diseases of the gastrointestinal tract.

Stem bark methanolic extract of Bauhinia thonningii (Schum) demonstrates gastroprotective properties against in vivo ethanol-induced injury

Background: Stomach ulcer is one of the diseases that many patients suffer from all over the world, and it causes damage to the intestinal wall. Some research has shown that Bauhinia thonningii extract, which has been traditionally used to treat a variety of ailments, including stomach ulcers, has powerful antioxidant and mucus-increasing properties. Objective:This research is aimed at studying the mechanism(s) through which methanolic (MBST) and chloroform (CBST) extracts of B. thonningii stem bark protects against ethanol-induced stomach damage in rats. Material and Methods: MBST and CBST were evaluated in vivo for their cytoprotective qualities employing stomach acidity, mucus content, macroscopic and microscopic methods, lipid peroxidation, nitric oxide, mass spectroscopy, 2D gel electrophoresis, and biochemical indicators. These extracts were tested in vitro on lipopolysaccharide/interferon-stimulated rat cells. Additionally, in-vivo, and in-vitro toxicity investigations were conducted. FRAP, DPPH, and ORAC tests were used to determine the antioxidant activity of MBST and CBST. Chemical and spectroscopic approaches were used to analyze the phytochemistry of MBST and CBST.Results: The gross and histological characteristics of B. thonningii proved its anti-ulcerogenic effects. MBST has gastroprotective effects by modulating lipid peroxidation and proteomics indicators [heat shock protein (Hsp60), disulfide isomerase (ERp60), protein disulfide-isomerase, creatine kinase B, cytosolic malate dehydrogenase, peroxiredoxin-6, and ATP synthase]. MBST and CBST have substantial impacts on nitric oxide both in-vitro and in-vivo. In comparison to CBST, methanolic extract (MBST) demonstrated greater gastroprotective properties, polyphenolic content, and antioxidant activity. The plant extracts did not show any toxicity in-vitro or in-vivo. MBST shows anti-ulcer action, which may be ascribed to its ability to reduce ethanol-triggered oxidative injury, to intervene in proteomic mechanisms, and to modulate nitric oxide.Conclusion:The present study found that stem bark extracts of Bauhinia thonningii Schum have cytoprotective activities against in vivo ethanol-induced damage due to its powerful antioxidant and mucus-increasing capabilities. Bauhinia thonningii warrants more attention since it may provide an exciting novel medication for the treatment of acute erosive gastropathy.Keywords: Bauhinia thonningii Schum;polar and non-polar extraction; peptic ulcer; nitric oxide; proteomics

Core-shell nanosystems designed for effective oral delivery of polypeptide drugs.

The stomach acid degradation, mucus clearance and intestinal epithelial impermeability severely limit the oral delivery of polypeptide drugs. To simultaneously address the three major barriers, novel self-assembled core-shell nanosystems (CA-NPs) were designed. The fabricated shell of citric acid cross-linked carboxymethyl cellulose (CA-CMC) wrapped on core nanoparticles (HA-NPs) maintained the integrity of CA-NPs in the stomach. When CA-NPs passed through the stomach, the CA-CMC shell was gradually degraded to release the core HA-NPs in the intestine. HA-NPs with numerous hydrophilic groups and mannose side chains rapidly penetrated through the mucus layer and efficiently transcellular transported via the glucose transporter (GLUT)-mediated and paracellular transport through reversible opening of tight junctions (TJs) by CA-CMC. The oral bioavailability and therapeutic effects of CA-NPs-loaded polypeptide colistin against Escherichia coli (E. coli) bacteremia in mice were significantly increased compared with the native colistin, respectively. Good safety was observed following oral daily delivery for 14 consecutive days. Thus, CA-NPs may offer a promising strategy for the oral delivery of polypeptide drugs.

Incidence of parasitic infection in adult and juvenile Clarias gariepinus in a private fish farm, Yola, Adamawa state

The study was conducted in Gesedaddo’s farm, Yola, Adamawa state, Nigeria to determine the prevalence of parasites infecting Clarias gariepinus between June to November, 2016. A total of one hundred and thirty-two (132) fish were sampled for parasitic investigation. Out of these, cultured adults (66) and cultured juveniles (66) respectively were procured from the farm and examined for parasites using the keys of fresh water fish parasite pictorial guide and were examined for parasitic infections using direct wet mount microscopy and stained smears. A total number of 43 adult Clarias gariepinus were infected out of which 132 parasites were identified, while in juvenile Clarias gariepinus, a total number of 10 fish were infected in which 30 parasites were identified in Gesedaddo’s farm. Seven (7) classes of parasites and eleven (11) parasite species, which are namely, Piscinoodinium, (Dinoflagellata), Coccidia, Spironucleus vortens, (Flagellata), Chilodonella, Tetrehymena, (Motile ciliate), Capillaria, Contracaecum, (Nematoda), Microsporidians, (Protozoa), Saprolegnia sp, (Oomycota), Digeneans, and Planarian (Trematoda) were recorded from the gills, stomach, intestine, and skin mucus of the cultured Clarias gariepinus on the farm. Parasitic infestation was higher in the intestine with 63 (47.73) and the least was identified 6 (4.55) on the skin for adult Clarias gariepinus while the highest number of parasites identified in juvenile Clarias gariepinus was found on the skin with total number of 11 (36.67). Among the class of parasites identified, it was recorded that the highest parasitic load occurred most in the class protozoan with 45 (34.09%) and 17 (56.67) in adult and Juvenile C. gariepinus respectively. The Chi square value shows that there was no significant difference (p>0.05) between the prevalence and intensity of parasitic infection in adults and juvenile C. gariepinus based on sex. Parasitic infestations in the adult and juvenile female were significantly higher than in the adult and juvenile male in cultured Clarias gariepinus. There was a significant difference between incidence of infestation, standard length and body weight of Clarias gariepinus while there was no significant difference (p> 0.05) between parasitic load.

Interleukin-13 level accompanying with Helicobacter pylori gastric infection in Kirkuk city Abstract

Background: Helicobacter pylori recognized as the most common cause of chronic gastritis and an important pathogenic factor in peptic ulcer, after colonization and stomach mucus layers caused increase in the levels of anti-inflammatory cytokine such as IL-13.
 The aims of this study is compare of IL-13 levels among treated patients with H. Pylori gastric infection, patients with H. Pylori gastric infection without treatment and healthy person
 Materials and Methods: The study was conducted in Kirkuk city from the September 2020 to March 2020, ELISA test used for interleukin -13 with peptic ulcer diseases (PUD).
 Results: Elevated levels of IL-13 reported in patients with acute and chronic H. pylori gastric infection compared to control group (44.74+8.18). A moderate significant in IL-13 level determined in infected patients without treatment, previously treated patients (140.12+45.36 vs 105+22.71). While, there was a high significant difference when these two groups and compared with the control group (44.74+8.18)).
 Conclusion: IL-13 levels is highest in patients with H. pylori gastric infection in compare healthy person.

Bacteria-targeting chitosan/carbon dots nanocomposite with membrane disruptive properties improve eradication rate of Helicobacter pylori

We designed a bacteria-targeting and membrane disrupting nanocomposite for successful antibiotic treatment of Helicobacter pylori (H. pylori) infections in the present study. The antibacterial nanocomposite was prepared from thiolated-ureido-chitosan (Cys-U-CS) and anionic poly (malic acid) (PMLA) via electrostatic interaction decorated with dual functional ammonium citrate carbon quantum dots (CDs). Cys-U-CS serves as a targeting building block for attaching antibacterial nanocomposite onto bacterial cell surface through Urel-mediated protein channel. Simultaneously, membrane disrupting CDs generate ROS and lyse the bacterial outer membrane, allowing antibiotics to enter the intracellular cytoplasm. As a result, Cys-U-CS/PMLA@CDs nanocomposite (UCPM-NPs) loaded with the antibiotic amoxicillin (AMX) not only effectively target and kill bacteria in vitro via Urel-mediated adhesion but also efficiently retain in the stomach where H. pylori reside, serving as an effective drug carrier for abrupt on-site release of AMX into the bacterial cytoplasm. Furthermore, since thiolated-chitosan has a mucoadhesive property, UCPM-NPs may adhere to the stomach mucus layer and pass through it swiftly. According to our results, bacterial targeting is crucial for guaranteeing successful antibiotic treatment. The bacteria targeting UCPM-NPs with membrane disruptive ability may establish a promising drug delivery system for the effective targeted delivery of antibiotics to treat H. pylori infections.

Evaluation of the effect of hydroalcoholic and flavonoid-enriched extracts of Dracocephalum kotschyi on indomethacin-induced gastric ulcer in rats.

Background and purpose:Dracocephalum kotschyi (Zaringiah) is a fragrant wild medicinal plant found in Iran. Traditionally, it is used for the treatment of rheumatism, asthma, and gastrointestinal ailments. So far no investigation has been done on the beneficial or side effects of D. kotschyi on peptic ulcer. Therefore, this research was performed to find out whether D. kotschyi extract would induce peptic ulcer or could alleviate existing peptic ulcer.Experimental approach:Effect of hydroalcoholic (DKHE) and flavonoid extracts (DKFE) of D. kotschyi were determined in normal or indomethacin-induced gastric ulcer rats (n = 6) and compared with the vehicle and ranitidine treated controls. All the treatments were carried out orally and 24 h later the stomach mucus was visually examined for peptic ulcers. A section of the stomach was taken for microscopic histopathological examinations while another section of the stomach was used for measurement of myeloperoxidase (MPO) and malondialdehyde (MDA) activities.Findings/Results:Oral administration of the DKHE and DKFE alone, did not cause any sign of gastric ulcer induction. The D. kotschyi extracts not only didn’t aggravate the induced ulcer but also significantly prevented the severity of gastric ulcer induction by indomethacin. In addition, DKHE and DKFE inhibited MPO (up to 58.2%) and MDA (up to 44.2%) activities indicating their anti-inflammatory and antioxidant potential action on the stomach-induced ulcer.Conclusion and implication:Usage of D. kotschyi extracts is not associated with gastric ulcer induction and its co-administration with NSAIDs would be beneficial for controlling both the inflammation and preventing gastric ulcer in diseases such as rheumatism.

Smart drug delivery against Helicobacter pylori: pectin-coated, mucoadhesive liposomes with antiadhesive activity and antibiotic cargo.

The first step in the development of Helicobacter pylori pathogenicity is the receptor-mediated adhesion to the gastric epithelium. Inhibition of outer membrane proteins of H. pylori (e.g. BabA) by antiadhesive drugs will contribute to reduced recolonization and infection. Pectin from apple inhibits the BabA and LPS-mediated adhesion of H. pylori to human stomach cells. Pectin-coated liposomes with encapsulated amoxicillin were characterized for polydispersity, zeta potential, encapsulation efficiency, stability, and amoxicillin release. Coated liposomes did not influence the viability of AGS and HT29-MTX cells up to 100 μg/mL but exert cytotoxicity against H. pylori at 10 μg/mL. Pectin-coating of liposomes provoked direct interaction and subsequent binding of the particles to surface structures of H. pylori, and interaction with mucus from porcine stomach and mucus secreted by HT29-MTX cells. Laser scanning microscopy of H. pylori and AGS cells together with liposomes indicated co-aggregation. The mucoadhesive effect seems interesting as stomach cells are covered by a mucus layer. H. pylori is able to penetrate and cross the mucin rapidly to reach pH-neutral epithelium to escape the acidic environment, followed by interaction with epithelial cells. In summary, all experimental evidence is consistent with a specific interaction of pectin-coated liposomes with mucins and surface structures of H. pylori. As the coated liposomes show mucoadhesion to the negatively charged mucins, docking to stomach mucin, mucus penetration, and recognition of and adhesion to H. pylori, they can be considered a novel type of multifunctional drug carriers for local antibiotic therapy against H. pylori. KEY POINTS: • Smart, multifunctional mucoadhesive liposomes • Specific targeting against BabA/LPS of Helicobacter pylori • Inhibition of bacterial adhesion of H. pylori to human host cells • Release of antibiotic cargo.

Immuno-histochemical features of chronic gastro-duodenitis in children with connective tissue dysplasia

Aim of the work: Better predicting the outcome of chronic gastro-duodenitis (CGD) and plan therapeutic intervention in children with connective tissue dysplasia (CTD) requires the accurate account of the pathological processes associated with CTD. Evaluations of histochemical and immune-histochemical changes in the small intestinal (SI) and stomach mucosa, particularly changes in collagen IV expression, improve the diagnostics of chronic CGD and predicting the disease outcome, providing a rationale for therapy approaches.The aim of research: to define histochemical and immuno-histochemical characteristics of stomach and duodenal mucus in children with CGD combined with CTD.Materials and methods. Stomach and SI biopsies from 63 children with CTD were examined using histological, histochemical and immune-histochemical approaches. Collagen Type IV (Ab-3) expression in each group was measured indirectly via streptavidin-peroxidase assay (Thermo Scientific), while the content of neutral glycosaminoglycanes was examined by PAS-staining.Results. Most patients without CTD have elevated PAS-reaction OR=7,0 (CI 1,14–42,971), when 87.5 % of children with CGD on a CTD background show significant decrease or absence of PAS-positive staining. The highest number of children with PAS-negative staining was identified in the groups with pronounced CTD. In children with the combined pathologies, the intensity of Collagen IV expression in BM of surface and glandular epithelium is 1.72 times (р=0.003) higher than in children without dysplasia while its spread is also 1.6 times higher (р=0.009)Conclusions. The greatest number of children having PAS-negative staining was found in a group with well manifested CTD, which reflects the changes in saliva production, the decrease in mucins and mucoids, and also changes in physicochemical properties of the mucus that lead to a true mucus dystrophy. In children having CGD combined with CTD, the Collagen IV expression in BM of surface and glandular epithelium is 1.72 times higher than in children without dysplasia, while its spread is 1.6 times higher. This indicates the damage of epithelial and endothelial BM and is one of the major causes of fibrosis development.

The gastro protective effects of Cibotium barometz hair on ethanol-induced gastric ulcer in Sprague-Dawley rats.

Background Cibotium barometz is a medical herb used traditionally in the Malaysian peninsula for several ailments, including gastric ulcer. The aim of this study was assessment the anti-ulcer effects of C. barometz hair on ethanol-induced stomach hemorrhagic abrasions in animals. Seven groups of Sprague Dawley (SD) rats were administered 10% Tween 20 in the normal control and ulcer control groups, and omeprazole 20 mg/kg and 62.5, 125, 250, and 500 mg/kg of C. barometz hair extract in the experimental groups. After 60 min, the normal control group of rats was orally administered 10% Tween 20, while absolute ethanol was orally administered to the groups of ulcer control, omeprazole and experimental groups. Stomachs of the rats were examined macroscopically and histologically. Homogenates of stomachs were used to evaluate endogenous antioxidant enzyme activities.ResultsRats pre-fed with plant extract presented a significant decrease in the sore area, increased pH of gastric contents and preserved stomach wall mucus compared to the ulcer group. Histologically, rats pre-fed with C. barometz hair extract showed mild to moderate disruptions of the surface epithelium while animals pre-fed with absolute ethanol showed severe disruptions of the stomach epithelium with edema and leucocyte penetration of the submucosal layer. A Periodic acid Schiff (PAS) staining revealed that each rat pre-treated with the plant extract displayed an intense uptake of stomach epithelial glycoprotein magenta color compared to the ulcer control group. Immunohistochemical analysis revealed that rats pre-fed with the plant extract showed an up-regulation of the heat shock protein 70 (HSP70) and down-regulation of Bax proteins compared to ulcer control rats. Homogenates of the stomach tissue demonstrated significant increases in the endogenous antioxidant enzymatic activity and decreased lipid peroxidation (MDA) in rats pre-treated with C. barometz hair extract compared with the ulcer control rats. In acute toxicity, the liver and kidney revealed no hepatotoxic or nephrotoxic effects histologically.ConclusionsThe gastric cytoprotective action of C. barometz hair extract might be attributed to antioxidants, an increase in gastric pH, stomach mucus preservation, increased endogenous antioxidant enzymes, decreased lipid peroxidation, up-regulation of HSP70 and down-regulation of Bax proteins.

Intestinal mucus acts is a maturation factor for dendritic cells

BackgroundGastrointestinal (GI) epithelial cells are covered by a thick layer of mucus which acts as a barrier, shielding the host epithelium from the luminal contents. Secreted mucus is expelled from goblet cells scattered throughout the GI tract, while adherent mucins are found on all epithelial cells. Mucus consists of highly glycosylated mucin proteins, primarily MUC2. Beneath the mucus and epithelial layer lies the lamina propria which contains multiple immune cell types. Intestinal dendritic cells (DCs) are professional antigen presenting cells capable of extending projections through the epithelium to sample antigen from the mucus layer and intestinal lumen. In this way, DCs are capable of interacting with antigens and metabolites from the intestinal microbiome. DCs act as sentinels in the GI tract by capturing and processing antigen, undergoing maturation, and regulating immune responses via production of cytokines. Previous studies have demonstrated that DCs are capable of extending processes through the mucus layer or acquiring antigen from antigen‐presenting goblet cells. However, little is known about the effect of mucus recognition by DCs and how this affects interaction with the microbiome. We hypothesize that intestinal mucin glycans stimulate monocytes toward DC lineages, thereby acting on innate immunity and immune/microbiota cross talk.MethodsTo assess the role of mucus in DC maturation and cytokine production the human monocyte cell line THP‐1 were matured to DC by stimulation with IL‐4 and GM‐CSF. Alternatively THP‐1 cells were stimulated with human stool mucus, mucus producing human cell line HT29‐MTX secreted mucus, pig stomach mucus or O‐linked mucus glycans. Mucus‐stimulated THP‐1 cells or IL‐4, GM‐CSF DCs were subjected to bacterial lipopolysaccharide (100 ng/ml LPS) for 3 hrs. Cells were analyzed by flow cytometry for mature DC markers CD11c and HLA and supernatants were examined for TNF production by ELISA. Human blood monocytes were isolated from whole blood and processed in the same manner.ResultsFlow cytometry data demonstrated that THP‐1 cells and human blood monocytes could be stimulated towards a DC‐like phenotype with IL‐4, GM‐CSF based on increased expression of CD11c, CD83 and HLA. Introduction of LPS resulted in an enhanced secretion of TNF in DCs compared to unstimulated monocytes or THP‐1 cells (8‐fold higher TNF). Interestingly, the presence of stool, pig stomach or HT29‐MTX cell‐derived mucus produced an increase in the CD83 hi CD11chi and CD11chiHLAhi DC populations from unstimulated THP‐1 cells. This increased DC population was also observed in gross morphology as mucus stimulated THP‐1s presented with increased diameter and projections. The ability of DCs to perform bacterial uptake in the presence of mucus was assessed using fluorescent carboxyfluorescein diacetate succinimidyl ester (CFDA‐SE) labeled bacteria. Mucus did not alter TNF production in unstimulated or LPS‐treated THP‐1 or in unstimulated or LPS‐treated DCs. However human and HT29‐MTX mucus did increase the CD11chiHLAhi population among mucus and LPS‐treated cells.ConclusionsTogether, this data indicates that intestinal mucus may act as a DC maturation factor and works to prime DC for interaction with members of the gut microbiota. This action of mucins has far‐reaching implications for immune interactions with the host and the intestinal microbiomeSupport or Funding InformationT32 DK007664

Helicobacter pylori strains vary cell shape and flagellum number to maintain robust motility in viscous environments.

The helical shape of the human stomach pathogen Helicobacter pylori has been suggested to provide mechanical advantage for penetrating the viscous stomach mucus layer. Using single-cell tracking and quantitative morphology analysis, we document marked variation in cell body helical parameters and flagellum number among H. pylori strains leading to distinct and broad speed distributions in broth and viscous gastric mucin media. These distributions reflect both temporal variation in swimming speed and morphologic variation within the population. Isogenic mutants with straight-rod morphology showed 7-21% reduction in speed and a lower fraction of motile bacteria. Mutational perturbation of flagellum number revealed a 19% increase in speed with 4 versus 3 median flagellum number. Resistive force theory modeling incorporating variation of both cell shape and flagellum number predicts qualitative speed differences of 10-30% among strains. However, quantitative comparisons suggest resistive force theory underestimates the influence of cell body shape on speed for helical shaped bacteria.

Глікопротеїни шлункового і дуоденального слизу при ульцерогенезі та при введенні екстракту фенугреку

The comparative evaluation of qualitative and quantitative composition of glycoproteins of gastric and duodenal wall surface layer of protective mucus in the normal, at the modeling of ulcers in rats and at the introduction to animals with ulcerative lesions of fenugreek extract carried out. It was shown in control (normally) the general level of glycosylation of glycoproteins gastric mucus is 1.7 times more than the duodenum. Under acute stress model ulceration in the stomach mucus decrease in hexosamine (1.4 times), galactose (2.2 times), fucose (1.3-fold) and an increase in NANA (3.6 times) observed. Under cysteamine model ulceration in duodenal mucus increase galactose (2.7 times), NANA (2.4 times), fucose (1.8-fold) but significant decrease in the amount of hexosamines 3 times compared to the control occurred. It was proved the protective effect of fenugreek extract to the wall surface mucus of the stomach and duodenum mucosa under conditions modeling ulceration in rats.

Comparison the Sensitivity of Stomach Mucus Touching Cytology and Urease Rapid Test in <italic>Helicobacter Pylori </italic> Diagnosis in Endoscopies Patients with Gastritis or Peptic Ulcer

Abstract This article does not have abstract.

Divergent Mechanisms of Interaction of Helicobacter pylori and Campylobacter jejuni with Mucus and Mucins

Helicobacter pylori and Campylobacter jejuni colonize the stomach and intestinal mucus, respectively. Using a combination of mucus-secreting cells, purified mucins, and a novel mucin microarray platform, we examined the interactions of these two organisms with mucus and mucins. H. pylori and C. jejuni bound to distinctly different mucins. C. jejuni displayed a striking tropism for chicken gastrointestinal mucins compared to mucins from other animals and preferentially bound mucins from specific avian intestinal sites (in order of descending preference: the large intestine, proximal small intestine, and cecum). H. pylori bound to a number of animal mucins, including porcine stomach mucin, but with less avidity than that of C. jejuni for chicken mucin. The strengths of interaction of various wild-type strains of H. pylori with different animal mucins were comparable, even though they did not all express the same adhesins. The production of mucus by HT29-MTX-E12 cells promoted higher levels of infection by C. jejuni and H. pylori than those for the non-mucus-producing parental cell lines. Both C. jejuni and H. pylori bound to HT29-MTX-E12 mucus, and while both organisms bound to glycosylated epitopes in the glycolipid fraction of the mucus, only C. jejuni bound to purified mucin. This study highlights the role of mucus in promoting bacterial infection and emphasizes the potential for even closely related bacteria to interact with mucus in different ways to establish successful infections.