Mucin Layer Research Articles

Enhanced creaminess of plant-based milk via enrichment of papain hydrolyzed oleosomes

There is an increased consumer demand for plant-based milk in substituting dairy milk due to the ethical, health concerns and environmentally-friendly choice. However, perceived creaminess as dominant attributes present a big challenge in consumer acceptance for those milk alternatives. In this study, we developed a novel and easily scalable strategy to enhance the creaminess of soy milk via enrichment of oleosomes. The soybean oleosome creams were extracted and hydrolyzed with papain, resulting in formation of oil droplets with more phospholipid and less protein at the surface, which significantly reduce friction coefficient in the presence of saliva (from 0.15 to 0.03 at a speed around 50 mm/s). Moreover, blending papain-hydrolyzed oleosome creams with raw soy milk enables the creation of a plant-based milk that matches the nutritional profile, lubrication properties, and creaminess of full-fat dairy milk. QCM-D and passive microrheology were employed to characterize hydration of oleosomes into the mucin layer and relevant viscosity change, suggesting that papain hydrolyzed oleosome might decrease friction coefficient via hydration lubrication mechanism. This approach could be applied to enhance the creaminess mouthfeel and nutritional profile of plant-based milk.

A Comprehensive Review about Risks of Type-II Diabetes on Ocular Tear Film

Millions of people worldwide suffer from diabetes mellitus (DM), which can lead to systemic issues in a number of organs. Ocular problems, such as dry eye syndrome (DES), are among its less well-known side effects. This review delves into the interactions between diabetes and the composition of tear films, emphasizing alterations in the mucin, aqueous and lipid layer. Dry eye symptoms are exacerbated by induced changes in the components of the tear film in diabetes DM, which lead in decrement in tear production, increment in tear evaporation and tear film instability. Lipid layer is a lubricant, that reduces friction between the ocular surface and the eyelids which promotes high-quality, smooth refractive surface. The lacrimal function unit shields the tear film, preserves the normal function of the ocular surface. The mucin layer is secreted by the conjunctival goblet cells, in hyperglycemia the functionality of the cells are reduced thus, the mucin secretion is also altered which causes instability of the tear film. Diabetic patients can have their tear film integrity assessed with the help of diagnostic methods like Schirmer's Test and Tear Break- Up Time (TBUT). In order to relieve symptoms and maintain ocular health, there should be a complete management of diabetes and the induced tear film disorders.

Aging by autodigestion.

The mechanism that triggers the progressive dysregulation of cell functions, inflammation, and breakdown of tissues during aging is currently unknown. We propose here a previously unknown mechanism due to tissue autodigestion by the digestive enzymes. After synthesis in the pancreas, these powerful enzymes are activated and transported inside the lumen of the small intestine to which they are compartmentalized by the mucin/epithelial barrier. We hypothesize that this barrier leaks active digestive enzymes (e.g. during meals) and leads to their accumulation in tissues outside the gastrointestinal tract. Using immune-histochemistry we provide evidence in young (4 months) and old (24 months) rats for significant accumulation of pancreatic trypsin, elastase, lipase, and amylase in peripheral organs, including liver, lung, heart, kidney, brain, and skin. The mucin layer density on the small intestine barrier is attenuated in the old and trypsin leaks across the tip region of intestinal villi with depleted mucin. The accumulation of digestive enzymes is accompanied in the same tissues of the old by damage to collagen, as detected with collagen fragment hybridizing peptides. We provide evidence that the hyperglycemia in the old is accompanied by proteolytic cleavage of the extracellular domain of the insulin receptor. Blockade of pancreatic trypsin in the old by a two-week oral treatment with a serine protease inhibitor (tranexamic acid) serves to significantly reduce trypsin accumulation in organs outside the intestine, collagen damage, as well as hyperglycemia and insulin receptor cleavage. These results support the hypothesis that the breakdown of tissues in aging is due to autodigestion and a side-effect of the fundamental requirement for digestion.

Studies on the Probiotic, Adhesion, and Induction Properties of Artisanal Lactic Acid Bacteria: to Customize a Gastrointestinal Niche to Trigger Anti-obesity Functions.

The primary goals of this work are to explore the potential of probiotic lactic acid bacteria's (LAB) mucin/mucus layer thickening properties and to identify anti-obesity candidate strains that improve appropriate habitat for use with the Akkermansia group population in the future. The HT-29 cell binding, antimicrobial properties, adhesion to the mucin/mucus layer, growth in the presence of mucin, stability during in vitro gastrointestinal (GI) conditions, biofilm formation, and mucin/mucus thickness increment abilities were all assessed for artisanal LAB strains. Sixteen LAB strains out of 40 were chosen for further analysis based on their ability to withstand GI conditions. Thirteen strains remained viable in simulated intestinal fluid, while most showed high viability in gastric juice simulation. Furthermore, 35.9-65.4% of those 16 bacteria adhered to the mucin layer. Besides, different lactate levels were produced, and Streptococcus thermophilus UIN9 exhibited the highest biofilm development. In the HT-29 cell culture, the highest mucin levels were 333.87µg/mL with O. AK8 at 50mM lactate, 313.38µg/mL with Lactobacillus acidophilus NRRL-B 1910 with initial mucin, and 311.41µg/mL with Lacticaseibacillus casei NRRL-B 441 with initial mucin and 50mM lactate. Nine LAB strains have been proposed as anti-obesity candidates, with olive isolates of Lactiplantibacillus plantarum being particularly important due to their ability to avoid mucin sugar consumption. Probiotic LAB's attachment to the colonic mucosa and its ability to stimulate HT-29 cells to secrete mucus are critical mechanisms that may support the development of Akkermansia.

Effect of Endurance Exercise Training on Gut Microbiota and ER Stress

Regular exercise as part of one’s lifestyle is well-recognized for its beneficial effect on several diseases such as cardiovascular disease and obesity; however, many questions remain unanswered regarding the effects of exercise on the gut environment. This study aimed to investigate the impact of long-term endurance exercise on modulating inflammation and endoplasmic reticulum (ER) stress. Fifteen-week-old male Sprague-Dawley (SD) rats were subjected to six months of endurance treadmill training, while age-matched controls remained sedentary. Results showed that IL-6 mRNA levels in colon tissues were significantly higher in the exercise group compared to the sedentary group. Exercise activated a significant ER stress-induced survival pathway by increasing BiP and phosphorylation of eIF2α (p-eIF2α) expressions in the liver and colon, while decreasing CHOP in the liver. Gene expressions of MUC2, Occludin, and Claudin-2 were increased in the colon of the exercise group, indicating enhanced intestinal integrity. Furthermore, the data showed a positive correlation between microbiota α-diversity and BiP (r = 0.464~0.677, p < 0.05). Populations of Desulfovibrio C21 c20 were significantly greater in the exercise group than the sedentary group. Additionally, predicted functions of the gut microbial community in terms of enzymes and pathways supported the enhancement of fatty-acid-related processes by exercise. These findings suggest that prolonged endurance exercise can affect the colon environment, which is likely related to changes in inflammation, ER stress, mucin layers and tight junctions, associated with modifications in the gut microbiome.

Multifunctional cerium oxide nanozymes with high ocular surface retention for dry eye disease treatment achieved by restoring redox balance

Dry eye disease (DED) is a kind of multifactorial ocular surface disease that displays ocular discomfort, visual disturbance, and tear film instability. Oxidative stress is a fundamental pathogenesis in DED. An imbalance between the reactive oxygen species (ROS) level and protective enzyme action will lead to oxidative stress, cell dysfunction, tear hyperosmolarity, and inflammation. Herein, a multifunctional cerium oxide nanozyme with high ocular surface retention property was designed to neutralize over-accumulated ROS and restore redox balance. Cerium oxide nanozymes were fabricated via branched polyethylenimine-graft-poly (ethylene glycol) nucleation and dispersion, followed by phenylboronic acid (PBA) functionalization (defined as Ce@PB). Due to the dynamic chemical bonding formation between the PBA segment and the cis-diol groups in the mucin layer of the tear film, Ce@PB nanozymes possess good adhesive capability to the ocular surface, thus extending the drug's retention time. On the other hand, Ce@PB nanozymes could mimic the cascade processes of superoxide dismutase and catalase to maintain intracellular redox balance. In vitro and in vivo studies suggest that such multifunctional nanozymes possess good biocompatibility and hemocompatibility. More importantly, Ce@PB nanozymes treatment in the animal model could repair corneal epithelial defect, increase the number of goblet cells and promote tear secretion, thus achieving an effective treatment for DED. Statement of significance•PBA-functionalized bPEI-g-PEG-based cerium oxide (Ce@PB) nanozymes were designed and fabricated.•The Ce@PB nanozymes have superoxide dismutase (SOD) and catalase (CAT) enzyme-like activity scavenging excessive intracellular reactive oxygen species (ROS).•The Ce@PB nanozymes demonstrate extended retention on the ocular surface and can effectively treat dry eye disease.

Effect of acetylcholinesterase inhibition on immune cells in the murine intestinal mucosa

The gastrointestinal tract (GI) is the largest immune organ whose function is controlled by a complex network of neurons from the enteric nervous system (ENS) as well as the sympathetic and parasympathetic system. Evolving evidence indicates that cross-communication between gut-innervating neurons and immune cells regulates many essential physiological functions including protection against mucosal infections. We previously demonstrated that following paraoxon treatment, 70 % of the mice were able to survive an oral infection with S. typhimurium, a virulent strain of Salmonella enterica serovar Typhimurium. The present study aims to investigate the effect that rivastigmine, a reversible AChE inhibitor used for the treatment of neurodegenerative diseases, has on the murine immune defenses of the intestinal mucosa. Our findings show that, similar to what is observed with paraoxon, administration of rivastigmine promoted the release of secretory granules from goblet and Paneth cells, resulting in increased mucin layer. Surprisingly, however, and unlike paraoxon, rivastigmine treatment did not affect overall mortality of infected mice. In order to investigate the mechanistic basis for the differential effects observed between paraoxon and rivastigmine, we used multi-color flowcytometric analysis to characterize the immune cell landscape in the intraepithelial (IE) and lamina propria (LP) compartments of intestinal mucosa. Our data indicate that treatment with paraoxon, but not rivastigmine, led to an increase of resident CD3+CD8+ T lymphocytes in the ileal mucosa (epithelium and lamina propria) and CD11b− CD11c+ dendritic cells in the LP. Our findings indicate the requirement for persistent cholinergic pathway engagement to effect a change in the cellular landscape of the mucosal tissue that is necessary for protection against lethal bacterial infections. Moreover, optimal protection requires a collaboration between innate and adaptive mucosal immune responses in the intestine.

Monobutyrin Can Regulate the Gut Microbiota, Which Is Beneficial for the Development of Intestinal Barrier Function and Intestinal Health in Weaned Mice.

In this study, we investigated the effect of monobutyrin (MB) on the gut microbiota and intestinal health of weaned mice. MB was administered via gavage to 21-day-old weaned mice. Samples of small intestinal and ileal contents were collected on day 1, day 7, and day 21 post-administration. Seven days of MB administration enhanced the mucin layer and morphological structure of the intestine and the integrity of the intestinal brush border. Both MB and sodium butyrate (SB) accelerated tight junction development. Compared to SB, MB modulated intestinal T cells in a distinct manner. MB increased the ratio of Treg cells in the small intestine upon the cessation of weaning. After 21 days of MB administration, enhancement of the villus structure of the ileum was observed. MB increased the proportion of Th17 cells in the ileum. MB facilitated the transition of the small intestinal microbiota toward an adult microbial community structure and enhanced the complexity of the microbial community structure. An increase in Th17 cells enhanced intestinal barrier function. The regulatory effect of MB on Th17 cells may occur through the intestinal microbiota. Therefore, MB can potentially be used to promote intestinal barrier function, especially for weaning animals, with promising application prospects.

Influence of structural organization on mucoadhesive properties of poloxamer-hyaluronic acid-based micelles and hydrogels: From molecular modelling to biointerfaces interactions

New pharmaceutical formulations have been proposed as strategies to improve transport and provide best conditions to control the drug release rate in specific biological environments, such as mucosa surfaces. Herein, formulations containing binary systems Poloxamer (PL) 407 15 % and PL 338 15 %, combined with hyaluronic acid, carrying the local anesthetic bupivacaine (BVC), were studied by molecular dynamics, while other structural parameters were determined by Dynamic Light Scattering for stablishing relationships with mucoadhesive properties and cytotoxicity evaluation. The binary system PL 407 15 %/PL 338 15 % exhibited a well-organized structural morphology, with more hydrated corona, and increased mucoadhesive properties over mucin layers. After hyaluronic acid (HA) incorporation, it was observed an increase on the force of detachment, possibly due to HA role as a linker among mucin layers independently of PL supramolecular structures. On the other hand, the addition of BVC or HA/BVC into the binary system decreased the force of detachment, as a response of augmented of compactness of these hydrogels caused by desolvation of PO core, showing the influence of all components and their chemical interactions into the structural organization and their biopharmaceutical performance relationships.

Analysis of the fecal metagenome in pelvic radiation survivors with or without chronic gastrointestinal toxicity.

e24041 Background: Whole pelvis radiation therapy (WPRT) is often used as a definitive or adjuvant treatment in patients with genitourinary, gynecologic, and gastrointestinal (GI) malignancies. Irradiation of nearby bowel can cause acute and chronic GI symptoms, which can affect patients’ quality of life. Radiation therapy has been shown to alter the microbial flora and may select for pathogenic species, which may enhance toxicity. Characteristics of the fecal metagenome in patients with or without chronic GI toxicity is unknown. Severity of GI symptoms can vary between patients who receive a similar radiation dose to normal bowel; therefore, there is a critical need to evaluate the interaction of RT and microbial species in the development of toxicity. Methods: An institutional database was used to identify survivors that completed WPRT for prostate, gynecologic, and anal cancer within the last 5 years. Patients were excluded if they had evidence of recurrent disease requiring additional therapy. Eligible patients were asked to participate via telephone. Consenting patients provided a stool sample and completed a customized PRO-CTCAE form (scale 1-5) assessing chronic GI symptoms. Comprehensive shotgun metagenomics were performed on stool. Stool was sequenced using an Illumina NextSeq500. The fecal metagenome in patients with or without chronic GI symptoms were compared. Patients were dichotomized by PRO-CTCAE diarrhea score (0-1 [mild] vs ≥2 [moderate-severe]). Raw reads were processed with Kneaddata for trimming, Kracken2 for taxonomic profiling, and Bracken for abundance estimation for bacterial, fungal and viral genomes using sequences from the National Center for Bioinformatics to determine quantitative genus and species differences. For microbial diversity assessments, estimated inverse Simpson and Shannon indices were performed. Results: Fecal metagenome and PRO-CTCAE results were available for 13 survivors. Thirty percent (n = 4) of patients reported moderate to severe diarrhea. The mean age was 66 years, 38% were male, 46% received concurrent or adjuvant chemotherapy, and the mean time from completion of WPRT to stool analysis was 34 months (range 14-62 months). Conventional radiation bowel constraints were met for each patient. Several species were enriched in patients with mild GI toxicity. Notably, Akkermansia muciniphilia had the largest differential enrichment in patients with without chronic GI toxicity. Conclusions: In this cohort of patients, A. muciniphilia, a mucin-degrading bacteria that modulates the gut barrier integrity and mucin layer thickness, was enriched in patients with no to mild diarrhea compared to patients with moderate to severe diarrhea. A. muciniphilia supplementation has been shown to decrease systemic inflammation in Western diet-fed mice. Evaluation of A. muciniphilia as a radioprotective gut bacterium warrants further evaluation.

A Systematic Study on the Physicochemical Interactions Between Polymeric Micelles and Mucin: Toward the Development of Optimal Drug Delivery Nanocarriers

AbstractThe optimal performance of drug delivery formulations, including polymeric nanoparticles, relies on particle distribution throughout the body and the interactions with biological barriers, particularly mucosal layers, which often limit their potential. A systematic and comprehensive study is presented through a multidisciplinary approach combining conventional and novel techniques for in vitro studies to understand the key molecular interactions between polymeric micelles and mucin. The results shows that polymeric micelles are integrates within the mucin layer, mirroring its viscoelastic properties, evidenced as a dissipation difference of 0.1 ± 0.44, measured by quartz crystal microbalance with dissipation. Surface‐enhanced Raman scattering reveals predominant hydrogen bonding within the mucin's hydrophilic core, while the isothermal titration calorimetry method confirms multiple non‐specific binding sites on the protein backbone. By performing the periodic acid‐Schiff stain assay, a binding amount of 0.20 mg of mucin per milligram of nanoparticles is quantified. Furthermore, motility studies show the surface binding of mucin on the polymeric nanoparticles influencing their Brownian motion. This study sheds light toward the improvement for a better drug delivery formulation and fabrication of optimal nanoparticle colloidal systems, which can advance translational drug delivery technologies into clinical application while enriching the field of surface and colloidal chemistry.

Carrageenan as a Potential Factor of Inflammatory Bowel Diseases.

Carrageenan is a widely used food additive and is seen as a potential candidate in the pharmaceutical industry. However, there are two faces to carrageenan that allows it to be used positively for therapeutic purposes. Carrageenan can be used to create edible films and for encapsulating drugs, and there is also interest in the use of carrageenan for food printing. Carrageenan is a naturally occurring polysaccharide gum. Depending on the type of carrageenan, it is used in regulating the composition of intestinal microflora, including the increase in the population of Bifidobacterium bacteria. On the other hand, the studies have demonstrated the harmfulness of carrageenan in animal and human models, indicating a direct link between diet and intestinal inflammatory states. Carrageenan changes the intestinal microflora, especially Akkermansia muciniphilia, degrades the mucous barrier and breaks down the mucous barrier, causing an inflammatory reaction. It directly affects epithelial cells by activating the pro-inflammatory nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) pathway. The mechanism is based on activation of the TLR4 receptor, alterations in macrophage activity, production of proinflammatory cytokines and activation of innate immune pathways. Carrageenan increases the content of Bacteroidetes bacteria, also causing a reduction in the number of short chain fatty acid (SCFA)-producing bacteria. The result is damage to the integrity of the intestinal membrane and reduction of the mucin layer. The group most exposed to the harmful effects of carrageenan are people suffering from intestinal inflammation, including Crohn disease (CD) and ulcerative colitis (UC).

Colon impairments and inflammation driven by an altered gut microbiota leads to social behavior deficits rescued by hyaluronic acid and celecoxib.

The exact mechanisms linking the gut microbiota and social behavior are still under investigation. We aimed to explore the role of the gut microbiota in shaping social behavior deficits using selectively bred mice possessing dominant (Dom) or submissive (Sub) behavior features. Sub mice exhibit asocial, depressive- and anxiety-like behaviors, as well as systemic inflammation, all of which are shaped by their impaired gut microbiota composition. An age-dependent comparative analysis of the gut microbiota composition of Dom and Sub mice was performed using 16S rRNA sequencing, from early infancy to adulthood. Dom and Sub gastrointestinal (GI) tract anatomy, function, and immune profiling analyses were performed using histology, RT-PCR, flow cytometry, cytokine array, and dextran-FITC permeability assays. Short chain fatty acids (SCFA) levels in the colons of Dom and Sub mice were quantified using targeted metabolomics. To support our findings, adult Sub mice were orally treatedwith hyaluronic acid (HA) (30 mg/kg) or with the non-steroidal anti-inflammatory agent celecoxib (16 mg/kg). We demonstrate that from early infancy the Sub mouse gut microbiota lacks essential bacteria for immune maturation, including Lactobacillus and Bifidobacterium genera. Furthermore, from birth, Sub mice possess a thicker colon mucin layer, and from early adulthood, they exhibit shorter colonic length, altered colon integrity with increased gut permeability, reduced SCFA levels and decreased regulatory T-cells, compared to Dom mice. Therapeutic intervention in adult Sub mice treated with HA, celecoxib, or both agents, rescued Sub mice phenotypes. HA treatment reduced Sub mouse gut permeability, increased colon length, and improved mouse social behavior deficits. Treatment with celecoxib increased sociability, reduced depressive- and anxiety-like behaviors, and increased colon length, and a combined treatment resulted in similar effects as celecoxib administered as a single agent. Overall, our data suggest that treating colon inflammation and decreasing gut permeability can restore gut physiology and prevent social deficits later in life. These findings provide critical insights into the importance of early life gut microbiota in shaping gut immunity, functionality, and social behavior, and may be beneficial for the development of future therapeutic strategies.

Current treatment options for dry eye syndrome in children

AIM: To analyze personalized therapy for dry eye syndrome (DES) in children, depending on the etiopathogenesis and severity of the disease.
 MATERIAL AND METHODS: In total, 187 children aged 3–17 years with DES were treated. Ophthalmic medicines registered in Russia from the group of local rehydrants replacing tear fluid and stabilizing tear film were used, and a comparative analysis of their effectiveness was carried out.
 RESULTS: An individual approach was implemented, and personalized therapy focused on the individual tolerability and effectiveness of medicines was developed. The principle of DES therapy is to replenish the lacrimal fluid deficiency and stabilize all layers of the tear film, considering the etiopathogenesis and severity of clinical symptoms. At this stage, the lipid layer of the tear film was normalized with the help of hypotonic oil-based preparations that can stabilize the lipid layer. All rehydrants of low, medium, and high viscosities contributed to the restoration of the water layer of the joint venture. The deficiency of the mucin layer of the tear film was compensated by hyaluronic acid and carboxymethylcellulose, which are part of the preparations that replace the tear film. The severity of DES associated with the intensity of the clinical changes in the conjunctiva and cornea was considered when designing the DES treatment regimen in children. In cases of mild and extremely severe severity, tear-replacement medicines of low viscosity showed the greatest therapeutic effectiveness. High-viscosity preparations and gels have been proven to be effective in moderate to severe DES. During the desquamation of the conjunctival and corneal epithelium, medicines with regenerating pharmacological action related to tissue repair simulators were included in the treatment regimen. Reparants included in the combined composition of tear-replacement medicines or monopreparations were used.
 CONCLUSION: The effectiveness of the DES treatment algorithm in children with various nosologies and features of etiopathogenesis was analyzed considering disease severity. The proposed schemes of personalized tear-replacement and reparative therapy make it possible to prevent a chronic disease course and occurrence of complications and preserve or restore visual acuity.

Quantification of diffusion coefficients of commonly used high-intensity sweeteners through mucin

Low- and no-calorie sweeteners reduce the amount of carbohydrates in foods and beverages. However, concerns about taste perception surrounding the role of non-nutritive sweeteners in the oral cavity remain unanswered. One of the parameters that influences taste perception is the diffusion coefficient of the sweetener molecules inside the mucin layer lining the mouth. This study investigated the impact of diffusion coefficients of common high-intensity sweeteners on taste perception focusing on the sweeteners’ diffusion through mucin. Transwell Permeable Support well plates were used to measure diffusion coefficients of samples that were collected at specific intervals to estimate the coefficients based on concentration measurements. The diffusion coefficients of acesulfame-K, aspartame, rebaudioside M, sucralose, and sucrose with and without NaCl were compared. We found that different sweeteners show different diffusion behavior through mucin and that the presence of salt enhances the diffusion. These findings contribute insights into the diffusion of high-intensity sweeteners, offer a way to evaluate diffusion coefficients in real-time, and inform the development of products with improved taste profiles.

A32 CATHELICIDIN REGULATES GOBLET CELL MUCUS SECRETION DURING CITROBACTER RODENTIUM-INDUCED COLITIS

Abstract Background Colonic goblet cells by secreting Muc2 mucin and specific proteins is critical for physically entrapping and expelling invading enteropathogens. Thus, is not surprising that Muc2-/- littermates exhibit increased susceptibility to attaching/effacing Citrobacter rodentium colonization. The colonic epithelium also secretes small cathelicidin peptide, which potentially interacts intimately with goblet cells and was presumed to accumulate within the sterile inner mucus layer as a simple antimicrobial peptide defense. Aims To determine the effects of cathelicidin on mucin secretion in goblet cells during C. rodentium-induced colitis and the impact on the mucus barrier defense. Methods We used cathelicidin-deficient (Camp-/-) mice, mouse colonoids and human colonic LS174T like-goblet epithelial cells to elucidate the mechanisms by which cathelicidin regulates goblet cell secretions. Results Camp -/- littermates infected with C. rodentium displayed increased fecal shedding and epithelial colonization. Camp-/- littermates at the peak of C. rodentium infection (7 dpi) showed a deficient mucin layer with fewer Alcian blue/PAS filled goblet cells and a reduction in fucose (UEA-1+) and N-acetylglucosamine (WGA+) glycoproteins. By transmission electron microscopy (TEM), goblet cells in Camp-/- colons were swollen and retained a large number of mucus granules during C. rodentium infection. C. rodentium infected Camp-/- littermates showed impaired reactive oxygen species (ROS) production and a transcriptomic profiling associated with decreased ROS biosynthesis and an increase in ROS negative regulators. In mucin producing LS174T colonic epithelial cells, human cathelicidin LL-37 promptly induced the secretion of goblet cell-associated TFF3 and RELMβ, via a ROS-dependent mechanism. Conclusions These findings revealed that mice lacking cathelicidin (Camp-/-) were more susceptible to C. rodentium colonization caused by defective goblet cell mucus and mucin-associated protein secretion via a ROS-dependent mechanism. Importantly, cathelicidin regulated mucus secretion revealing a non microbicidal action of this peptide with homeostatic properties on the colonic mucus barrier, critical in excluding luminal microbiota away from the epithelia to clear bacterial infections and restore gut homeostasis. Funding Agencies NSERC

Akkermansia muciniphila improves chronic colitis-induced enteric neuroinflammation in mice.

Inflammatory bowel diseases (IBD) are chronic diseases that are not fully understood. Drugs in use can only be applied for a short time due to their side effects. Therefore, research is needed to develop new treatment approaches. In addition, it has been proven that IBD causes degeneration in the enteric nervous system (ENS). In recent years, it has been discussed that probiotics may have positive effects in the prevention and treatment of inflammatory enteric degeneration. Akkermansia muciniphila (A. muciniphila) is an anaerobic bacterium found in the mucin layer of the intestinal microbiota. It has been found that the population of A. muciniphila decreases in the case of different diseases. In light of this information, the curative effect of A. muciniphila application on colitis-induced inflammation and enteric degeneration was investigated. In this study, 5 weeks of A. muciniphila treatment in Trinitro-benzene-sulfonic acid (TNBS)-induced chronic colitis model was investigated. Colon samples were examined at microscopic, biochemical, and molecular levels. Fecal samples were collected before, during, and after treatment to evaluate the population changes in the microbiota. Specific proteins secreted from the ENS were evaluated, and enteric degeneration was examined. As a result of the research, the ameliorative effects of A. muciniphila were shown in the TNBS colitis model-induced inflammation and ENS damage. In light of these results, A. muciniphila can potentially be evaluated as a microbiome-based treatment for IBD with further clinical and experimental studies.

Microbial risks associated with microplastics in the food chain and possible control measures (literature review). Part 1. Dietary intake and influence on the gut microbiota

Environmental contamination by polymer wastes and microplastics (MPs) has recently become important for health care, due to the emergence of a lot of evidence that MPs affect the health of living organisms, including humans.
 MPs commonly presented in drinking water and various groups of food products, and are found in human stool, colon tissue, and blood samples. When MPs are orally ingested, the first object for their interaction with the organism is the gastrointestinal microbiota. Considering the essential importance of the intestinal microbiota for human health, the study of the negative consequences of such contact becomes very important.
 The results of “in vitro” and “in vivo” experimental studies summarized in the review indicate MPs to have negative effects on the microbial community composition and of the intestinal barrier state, and are themselves subject to microbial degradation in the gastrointestinal tract. “In vivo” studies, the entry of MPs into the intestine is accompanied by an increase in α-diversity of the microbiota, presumably due to foreign microorganisms attached to the particles, including those in as part of biofilms formed on their surfaces.
 Competing with representatives of normal intestinal flora, these microorganisms are able to enzymatically degrade or overcome the mucosal barrier. Simultaneously the biofilm matrix associate with intestinal mucus and provides MPs particles with retention in the mucin layer and direct contact with the apical part of epitheliocytes. This leads to irritation, local inflammation, and damage to the intestinal barrier.
 MPs and their biotransformation products can also systemically affect the host organism, translocating from the intestine into the bloodstream.
 The review emphasizes that to identify and characterize the health risks associated with the intake of various MPs from food, studies assessing their interaction with the microbiota and biotransformation pathways in the intestine are necessary.

Strengthening the diffusion of sodium ions by interactions between gum Arabic and oral mucin

In present study, we explored the effect of mucin-gum arabic (GA) interactions on the structural changes of mucin network, as well as on the diffusion behaviors of sodium ions. Diffusion behaviors of sodium ions through the mucin/GA layer with various physicochemical properties were determined. Our results suggested that the introduction of GA induced the phase separation of mucin-GA binary system, which is largely driven by electrostatic interactions (electrostatic repulsion) and followed by the structural changes in the mucin layer. The mucin/GA mixed interconnected network with larger pores was formed, as revealed by transmission electron microscopy and atomic force microscopy observations, which contributed to the diffusion of sodium ions. Our findings might provide a deep understanding of GA for enhancing the salty taste perception.

Micro-interaction of montmorillonite-loaded nanoparticles with mucin promotes retention of betaxolol hydrochloride on the ocular surface and the tear film microenvironment

This work developed a triple-encapsulated nano-delivery system for topical and long-term glaucoma treatment. We encapsulated betaxolol hydrochloride (BH), a glaucoma drug loaded in refined acid-treated montmorillonite (RAMt), in hyaluronic acid/chitosan (HA/CS) cross-linked nanoparticles with high encapsulation efficiency and further wrapped them with Eudragit (ED) films to achieve dual sustained release. RAMt-BH-HA/CS@ED NPs exhibited excellent physicochemical properties for the sustained release of betaxolol hydrochloride. In vitro release experiments were performed, and the results showed that the drug release lasted for up to 8 h. Then, particle surface hydrophobicity experiments showed that the nanoparticles had both hydrophilic and hydrophobic properties. The ocular safety of the nanoparticles was confirmed by the chick embryo allantoic membrane assay and the rabbit blink frequency test. In the mucin-nanoparticle interaction experiments, the interaction between the nanoparticles and the mucin solution with high pH and low concentration (simulating the aqueous layer microenvironment of tears) was stronger than that with low pH and high concentration (simulating the tear mucin layer microenvironment of tears). Therefore, the nanoparticles showed excellent retention properties in tears and cornea. In vivo experiments in a rabbit model of elevated intraocular pressure demonstrated that the IOP-lowering effect was sustained for more than 12 hours. In conclusion, nanoparticles effectively lower IOP with excellent tolerability, and offer promising applications for long-term treatment of glaucoma.