Mucus Layer Research Articles

Human Mesofluidic Intestinal Model for Studying Transport of Drug Carriers and Bacteria Through a Live Mucosal Barrier.

The intestinal mucosal barrier forms a critical interface between lumen contents such as bacteria, drugs, and drug carriers and the underlying tissue. Current in vitro intestinal models, while recapitulating certain aspects of this barrier, generally present challenges with respect to imaging transport across mucus and uptake into enterocytes. A human mesofluidic small intestinal chip was designed to enable facile visualization of a mucosal interface created by growing primary human intestinal cells on a vertical hydrogel wall separating channels representing the intestinal lumen and circulatory flow. Type I collagen, fortified via cross-linking to prevent deformation and leaking during culture, was identified as a suitable gel wall material for supporting primary organoid-derived human duodenal epithelial cell attachment and monolayer formation. Addition of DAPT and PGE2 to culture medium paired with air-liquid interface culture increased the thickness of the mucus layer on epithelium grown within the device for 5 days from approximately 5 mm to 50 μm, making the model suitable for revealing intriguing features of interactions between luminal contents and the mucus barrier using live cell imaging. Time-lapse imaging of nanoparticle diffusion within mucus revealed a zone adjacent to the epithelium largely devoid of nanoparticles up to 4.5 hr after introduction to the lumen channel, as well as pockets of dimly lectin-stained mucus within which particles freely diffused, and apparent clumping of particles by mucus components. Multiple particle tracking conducted on the intact mucus layer in the chip revealed significant size-dependent differences in measured diffusion coefficients. E. coli introduced to the lumen channel were freely mobile within the mucus layer and appeared to intermittently contact the epithelial surface over 30 minute periods of culture. Mucus shedding into the lumen and turnover of mucus components within cells were visualized. Taken together, this system represents a powerful tool for visualization of interactions between luminal contents and an intact live mucosal barrier.

Nanoparticles as Drug Delivery Vehicles for People with Cystic Fibrosis.

Cystic Fibrosis (CF) is a life-shortening, genetic disease that affects approximately 145,000 people worldwide. CF causes a dehydrated mucus layer in the lungs, leading to damaging infection and inflammation that eventually result in death. Nanoparticles (NPs), drug delivery vehicles intended for inhalation, have become a recent source of interest for treating CF and CF-related conditions, and many formulations have been created thus far. This paper is intended to provide an overview of CF and the effect it has on the lungs, the barriers in using NP drug delivery vehicles for treatment, and three common material class choices for these NP formulations: metals, polymers, and lipids. The materials to be discussed include gold, silver, and iron oxide metallic NPs; polyethylene glycol, chitosan, poly lactic-co-glycolic acid, and alginate polymeric NPs; and lipid-based NPs. The novelty of this review comes from a less specific focus on nanoparticle examples, with the focus instead being on the general theory behind material function, why or how a material might be used, and how it may be preferable to other materials used in treating CF. Finally, this paper ends with a short discussion of the two FDA-approved NPs for treatment of CF-related conditions and a recommendation for the future usage of NPs in people with Cystic Fibrosis (pwCF).

Mind the Particle Rigidity: Blooms the Bioavailability via Rapidly Crossing the Mucus Layer and Alters the Intracellular Fate of Curcumin.

Overcoming intestinal epithelial barriers to enhance bioavailability is a major challenge for oral delivery systems. Desirable nanocarriers should simultaneously exhibit rapid mucus penetration and efficient epithelial uptake; however, they two generally require contradictory structural properties. Herein, we proposed a strategy to construct multiperformance nanoparticles by modifying the rigidity of amphiphilic nanostructures originating from soy polypeptides (SPNPs), where its ability to overcome multibarriers was examined from both in vitro and in vivo, using curcumin (CUR) as a model cargo. Low-rigidity SPNPs showed higher affinity to mucin and were prone to getting stuck in the mucus layer. When they reached epithelial cells, they tended to be endocytosed through the clathrin and macropinocytosis pathways and further transferred to lysosomes, showing severe degradation and lower transport of CUR. Increased particle rigidity generally improved the absorption of CUR, with medium-rigidity SPNPs bloomed maximum plasma concentration of CUR by 80.62-fold and showed the highest oral bioavailability. Results from monocultured and cocultured cell models demonstrated that medium-rigidity SPNPs were least influenced by the mucus layer and changes in rigidity significantly influenced the endocytosis and intracellular fate of SPNPs. Those with higher rigidity preferred to be endocytosed via a caveolae-mediated pathway and trafficked to the ER and Golgi, facilitating their whole transcytosis, and avoiding intracellular metabolism. Moreover, rigidity modulation efficiently induces the reversible opening of intercellular tight junctions, which synergistically improves the transport of CUR into blood circulation. This study suggested that rigidity regulation on food originated amphiphilic peptides could overcome multiple physiological barriers, showing great potential as natural building block toward oral delivery.

A Strategic Blend of Stabilizing Polymers to Control Particle Surface Charge for Enhanced Mucus Transport and Cell Binding.

Mucus layers, viscoelastic gels abundant in anionic mucin glycoproteins, obstruct therapeutic delivery across all mucosal surfaces. We found that strongly positively charged nanoparticles (NPs) rapidly adsorb a mucin protein corona in mucus, impeding cell binding and uptake. To overcome this, we developed mucus-evading, cell-adhesive (MECS) NPs with variable surface charge using Flash NanoPrecipitation, by blending a neutral poly(ethylene glycol) (PEG) corona for mucus transport with a small amount, 5 wt%, of polycationic dimethylaminoethyl methacrylate (PDMAEMA) for increased cell targeting. In vitro experiments confirmed rapid mucus penetration and binding to epithelial cells by MECS NPs, suggesting a breakthrough in mucosal drug delivery.

Microbial Fermentation and Therapeutic Potential of p-Cymene: Insights into Biosynthesis and Antimicrobial Bioactivity

p-Cymene (p-C) [1-methyl-4-(1-methylethyl)-benzene] is a monoterpene found in a variety of plants and has several biological activities, including antioxidant, anti-inflammatory, antimicrobial, and anticancer properties. This paper explores the microbial fermentation pathways involved in the biosynthesis of p-C, with an emphasis on its potential as a therapeutic agent. Through microbial and biochemical processes, p-C can be produced using renewable precursors such as limonene and 1,8-cineole. Recent advances in fermentation technology have enhanced the efficiency of p-C production, highlighting its role in various industries. Additionally, this paper reviews the antimicrobial bioactivity of p-C, focusing on its ability to inhibit pathogens and modulate immune responses. The integration of microbial biosynthesis and fermentation methods offers a sustainable approach to producing p-C for applications in the perfume, cosmetics, food, and pharmaceutical sectors. Understanding these biosynthetic pathways is crucial for advancing the use of p-C as a bio-based chemical with therapeutic potential. In particular, p-C inhibits the expression of cytokine signal 3 in intestinal inflammation and modulates antioxidant and immunomodulatory systems to protect barrier cells and maintain the mucus layer.

Dual-layer probiotic encapsulation using metal phenolic network with gellan gum-tamarind gum coating for colitis treatment

Probiotic oral therapy has been recognised as an effective treatment for inflammatory bowel disease (IBD). However, the efficacy of probiotics is often diminished due to their limited resistance to harsh gastrointestinal conditions. Therefore, the importance of designing innovative strategies for oral probiotic delivery for the effective treatment of IBD is increasingly recognised. In this study, we present a novel encapsulation strategy of Lactobacillus plantarum (L.P) using the dual-layer system consisting of a tannic acid‑calcium network and polysaccharide coating (gellan gum-tamarind gum) named L.P-C/T-G/T. This double-layer encapsulation system not only does not affect the normal proliferation of probiotics and provide protection, but also endows probiotics with more functions. More specifically, the acid resistance ability of the encapsulated probiotics is increased by 10 times, the free radical scavenging rate is enhanced by 5 times, and the intestinal retention time can be prolonged by 6–12 h. In the DSS-induced murine colitis model, it significantly alleviated colon shortening, inhibited ROS overexpression, and promoted the repair and regeneration of the mucus layer. This dual-layer encapsulation approach for a single probiotic demonstrates a significant advancement in probiotic delivery technology, offering hope for a comprehensive approach to the treatment of colitis and potentially other gastrointestinal disorders.

Water-soluble garlic polysaccharide (WSGP) improves ulcerative colitis by modulating the intestinal barrier and intestinal flora metabolites

WSGP has demonstrated significant potential for various bioactive effects. However, limited research has explored their anti-ulcerative colitis (UC) effects and mechanism on the colonic system and gut microbial metabolites. We evaluated the ameliorative effects of WSGP on the UC mice model. Using H&E to assess histological injury of colon morphology, AB-PAS staining to detect mucin secretion from goblet cells and the mucous layer, IF to evaluate the expression of intercellular tight junction proteins, ELISA to measure inflammatory factors, WB analysis to measure protein expression of inflammatory signaling pathways, RT-qPCR to quantify gene transcription of inflammatory factors, and LC-MS to analyze metabolites in mouse cecum contents. WSGP supplementation increased food intake, body weight, and colon length while reducing disease activity and histological scores in colitis-afflicted mice. WSGP mitigated colonic tissue damage and restored intestinal barrier integrity by suppressing NF-κB/STAT3 signaling, thereby decreasing gene transcription, protein expression of proinflammatory factors, and nitric oxide production. Additionally, WSGP improved UC by altering the variety of intestinal microbial metabolites. This study demonstrates that WSGP supplementation attenuates UC mice by suppressing the NF-κB/STAT3 signaling pathway, enhancing mucosal barrier function, reducing pro-inflammatory cytokines, and modulating gut microbial metabolites.

A mucoadhesive-to-penetrating nanomotors-in-hydrogel system for urothelium-oriented intravesical drug delivery

Intravesical therapy (IT) is widely used to tackle various urological diseases. However, its clinical efficacy is decreased by the impermeability of various barriers presented on the bladder luminal surface, including the urinary mucus layer and the densely packed tissue barrier. In this study, we report a mucoadhesive-to-penetrating nanomotors-in-hydrogel system for urothelium-oriented intravesical drug delivery. Upon intravesical instillation, its poloxamer 407 (PLX) hydrogel gelated and adhered to the urothelium to prolong its intravesical retention. The urea afterwards diffused into the hydrogel, thus generating a concentration gradient. Urease-powered membrane nanomotors (UMN) without asymmetric surface engineering could catalyze the urea and migrate down this concentration gradient to deeply and unidirectionally penetrate the urothelial barrier. Moreover, the intravesical hybrid system-delivered gemcitabine could effectively inhibit the bladder tumor growth without inducing any side effect. Therefore, our mucoadhesive-to-penetrating nanomotors-in-hydrogel system could serve as an alternative to IT to meet the clinical need for more efficacious therapeutics for urological diseases.Graphical

Possible sink of missing ocean plastic: Accumulation patterns in reef-building corals in the Gulf of Thailand

Individual coral polyps contain three distinct components—the surface mucus layer, tissue, and skeleton; each component may exhibit varying extent of microplastic (MP) accumulation and serve as a short- or long-term repository for these pollutants. However, the literature on MP accumulation in wild corals, particularly with respect to the different components, is limited. In this study, we investigated the adhesion and accumulation of MPs in four coral species, including both large (Lobophyllia sp. and Platygyra sinensis) and small (Pocillopora cf. damicornis and Porites lutea) polyp corals collected from Si Chang Island in the upper Gulf of Thailand. The results revealed that MP accumulation varied significantly among the four coral species and their components. Specifically, P. cf. damicornis exhibited the highest degree of accumulation (2.28 ± 0.34 particles g−1 w.w.) [Tukey's honestly significant difference (HSD) test, p < 0.05], particularly in their skeleton (52.63 %) and with a notable presence of high-density MPs (Fisher's extract test, p < 0.05). The most common MP morphotype was fragment, accounting for 75.29 % of the total MPs found in the coral. Notably, the majority of MPs were black, white, or blue, accounting for 36.20 %, 15.52 %, and 11.49 % of the samples, respectively. The predominant size range of MP particles was 101–200 μm. Nylon, polyacetylene, and polyethylene terephthalate (PET) were the prevalent polymer types, accounting for 20.11 %, 14.37 %, and 9.77 % of the identified samples, respectively. In the large polyp corals, while MP shapes, colors, and sizes exhibited consistent patterns, remarkable differences were noted in the polymer types across the three components. The findings of this study improve the understanding of MP accumulation and its fate in coral reef ecosystems, underscoring the need for further investigation into MP-accumulation patterns in reef-building corals worldwide.

Antibiotics damage the colonic mucus barrier in a microbiota-independent manner.

Antibiotic use is a risk factor for development of inflammatory bowel diseases (IBDs). IBDs are characterized by a damaged mucus layer, which does not separate the intestinal epithelium from the microbiota. Here, we hypothesized that antibiotics affect the integrity of the mucus barrier, which allows bacterial penetrance and predisposes to intestinal inflammation. We found that antibiotic treatment led to breakdown of the colonic mucus barrier and penetration of bacteria into the mucus layer. Using fecal microbiota transplant, RNA sequencing followed by machine learning, ex vivo mucus secretion measurements, and antibiotic treatment of germ-free mice, we determined that antibiotics induce endoplasmic reticulum stress in the colon that inhibits colonic mucus secretion in a microbiota-independent manner. This antibiotic-induced mucus secretion flaw led to penetration of bacteria into the colonic mucus layer, translocation of microbial antigens into circulation, and exacerbation of ulcerations in a mouse model of IBD. Thus, antibiotic use might predispose to intestinal inflammation by impeding mucus production.

146 The effects of antimicrobials and antimicrobial associated diarrhea on the fecal microbiome of the horse

Abstract Antibiotics are commonly given to horses to treat known bacterial infections or as prophylaxis against the development of infection. Diarrhea is a recognized adverse effect of antimicrobial administration in horses (antimicrobial associated diarrhea, AAD). In veterinary referral centers, AAD has a reported incidence of 22 to 94% (McGorum, 2010), while horses with AAD are 4.5 times more likely to die compared with horses with other types of colitis (Woods and Cohen, 1999). Although all antibiotics have potential to induce diarrhea, some have increased risk due to low oral absorption, biliary excretion, or enterohepatic recycling. The role of dysbiosis in the gut microbiota is a key feature in the pathogenesis of AAD. Disruption of commensal bacteria of the hindgut allows for pathogen overgrowth and alteration in microbial metabolic function. To date, 16S rRNA sequencing has been used to characterize the effects of penicillin, trimethoprim sulfa, doxycycline, erythromycin, ceftiofur, enrofloxacin, oxytetracycline and metronidazole on the fecal microbiome in healthy horses (Costa et al., 2015; Arnold et al., 2020; Liepman, 2022). Regardless of mechanism of action, antibiotics typically reduce diversity (species richness and evenness) and alter the bacterial community structure of the fecal microbiome, even when animals maintain normal health status and fecal character (Arnold et al., 2021). These effects typically require at least 30 days before the microbiome returns to baseline (Gomez et al, 2023). In horses with colitis, changes in the microbiome are often significant. Horses with AAD demonstrate the most severe disruption of the fecal microbiome compared with horses with Salmonella or undifferentiated colitis. These changes are evident from the phylum to species level, and include important phyla such as Bacteroidetes, Firmicutes, Fibrobacter and Verrucomicrobia (Arnold et al., 2020; Liepman, 2022; Costa et al., 2015). Alterations in the microbiota result in functional metabolic changes that are clinically manifested by diarrhea. Potential changes include alterations in the metabolism of bile acids, carbohydrates including short chain fatty acids, amino acids, lipids and proteins. There is also evidence that antimicrobials increase intestinal permeability via effects on tight junction proteins and by compromising the barrier function provided by the mucus layer between the enterocytes and gut lumen. Recent work comparing horses on antimicrobials that did and did not develop diarrhea confirm that horses with diarrhea have depletion of Verrocomicrobia and metabolites related to gastrointestinal barrier function (Arnold et al., 2021).

Functional Effects of Probiotic Lactiplantibacillus plantarum in Alleviation Multidrug-Resistant Escherichia coli-Associated Colitis in BALB/c Mice Model.

Multidrug-resistant Escherichia coli (MDR-E. coli) is a global health concern. Lactic acid bacteria (LAB) are important probiotics that have beneficial effects on health, and in recent years, their influences in preventing foodborne pathogens-induced colitis have attracted much attention. Therefore, this study aimed to investigate the oral administration of Lactiplantibacillus plantarum NWAFU-BIO-BS29 as an emerging approach to alleviate MDR-E. coli-induced colitis in BALB/c mice model. To illustrate the mode of action of NWAFU-BIO-BS29 interventions with the gut microbiota and immune responses, the changes on the colonic mucosal barrier, regulatory of the gene expressions of inflammatory cytokines, re-modulating the intestinal microflora, and changes in physiological parameters were studied. The results indicated that daily supplementation of 200 µL fresh bacteria for 7days had ameliorated the associated colitis and partially prevented the infection. The modes of action by ameliorating the inflammatory response, which destructed villous and then affected the intestinal barrier integrity, reducing the secretion of interleukins (6 and β) and tumor necrosis factor (TNF-α) in serum by 87.88-89.93%, 30.73-35.98%, and 19.14-22.32%, respectively, enhancing the expressions of some epithelial integrity-related proteins in the mouse mucous layer of mucins 2 and 3, Claudin-1, and Occludin by 130.00-661.85%, 27.64-57.35%, 75.52-162.51%, and 139.36-177.73%, respectively, and 56.09-73.58% for toll-like receptor (TLR4) in colon tissues. Notably, the mouse gut microbiota analysis showed an increase in the relative abundance of beneficial bacteria, including Lactobacillus, Bacteriodales bacterium, Candidatus Saccharimonas, Enterorhabdus, and Bacilli. Furthermore, the probiotic promoted the proliferation of epithelia and goblet cells by increasing short-chain fatty acids (SCFAs) levels by 19.23-31.39%. In conclusion, L. plantarum NWAFU-BIO-BS29 has potential applications and can be considered a safe dietary supplement to ameliorate the colitis inflammation symptoms of MDR-E. coli infection.

Design of Auto-Adaptive Drug Delivery System for Effective Delivery of Peptide Drugs to Overcoming Mucus and Epithelial Barriers.

Oral administration of peptide represents a promising delivery route, however, it is hindered by the harsh gastrointestinal environment, leading to low in vivo absorption. In this study, auto-adaptive protein corona-AT 1002-cationic liposomes (Pc-AT-CLs) are constructed with the characteristic of hydrophilic and electrically neutral surface properties for the encapsulation of liraglutide. BSA protein corona is used to coat AT-CLs reducing the adherence of mucus, and may fall off after penetrating the mucus layer. Transmucus transport experiment demonstrated that the mucus penetration amount of Pc-AT-CLs are 1.45 times that of AT-CLs. After penetrating the mucus layer, AT-CLs complete transmembrane transport by the dual action of AT and cationic surface properties. Transmembrane transport experiment demonstrated that the apparent permeability coefficient (Papp) of AT-CLs is 2.03 times that of CLs. In vivo tests demonstrated that Pc-AT-CLs exhibited a significant hypoglycemic effect and enhanced the relative bioavailability comparing to free liraglutide. Pc-AT-CLs protect liraglutide from degradation, facilitate its absorption, and ultimately improve its oral bioavailability.

Ex vivo electrical bioimpedance measurements and Cole modelling on the porcine colon and rectum

Different pathological changes in the large intestine wall, associated with the development of different chronic diseases, including colorectal cancer, could be reflected in electrical bioimpedance readings. Thickness and composition of the mucus bilayer covering it in the luminal side, abundance of bacteria of the intestinal microbiota, the permeability of the epithelium and inflammation are some of these. However, scientific literature on electrical passive properties of the large intestine is scarce. In this study, complex impedance measurements at 8 frequencies were carried out on 6 specimens of porcine colorectal tissue, within half ab hour post-mortem, obtained from a local abattoir. For 5 different distances, measured proximally from the border of the anus, 3 readings were taken at 3 different points with a tetrapolar probe. The results show 2 different dielectric dispersions in the α and β regions and it seems that there is a relationship between the values of resistivities and the thickness of the wall. Also, parameter values both for the Cole and the geometrical models are given. Another set of electrical bioimpedance readings was carried out in order to assess the effect of the mucus layer on electrical properties of the tissue. It seems that these layers are related to the low frequency dispersion. Finally, electrical passive properties of porcine colorectal tissue, reported in this work, give reference values and behaviour patterns that could be applied for further research in human medicine, based on bioimpedance measurements.

ELP1, the Gene Mutated in Familial Dysautonomia, Is Required for Normal Enteric Nervous System Development and Maintenance and for Gut Epithelium Homeostasis.

Familial dysautonomia (FD) is a rare sensory and autonomic neuropathy that results from a mutation in the ELP1 gene. Virtually all patients report gastrointestinal (GI) dysfunction and we have recently shown that FD patients have a dysbiotic gut microbiome and altered metabolome. These findings were recapitulated in an FD mouse model and moreover, the FD mice had reduced intestinal motility, as did patients. To understand the cellular basis for impaired GI function in FD, the enteric nervous system (ENS; both female and male mice) from FD mouse models was analyzed during embryonic development and adulthood. We show here that not only is Elp1 required for the normal formation of the ENS, but it is also required in adulthood for the regulation of both neuronal and non-neuronal cells and for target innervation in both the mucosa and in intestinal smooth muscle. In particular, CGRP innervation was significantly reduced as was the number of dopaminergic neurons. Examination of an FD patient's gastric biopsy also revealed reduced and disoriented axons in the mucosa. Finally, using an FD mouse model in which Elp1 was deleted exclusively from neurons, we found significant changes to the colon epithelium including reduced E-cadherin expression, perturbed mucus layer organization, and infiltration of bacteria into the mucosa. The fact that deletion of Elp1 exclusively in neurons is sufficient to alter the intestinal epithelium and perturb the intestinal epithelial barrier highlights a critical role for neurons in regulating GI epithelium homeostasis.

Human milk oligosaccharide 2’-fucosyllactose protects against high-fat diet-induced obesity by changing intestinal mucus production, composition and degradation linked to changes in gut microbiota and faecal proteome profiles in mice

ObjectiveTo decipher the mechanisms by which the major human milk oligosaccharide (HMO), 2’-fucosyllactose (2’FL), can affect body weight and fat mass gain on high-fat diet (HFD) feeding in mice. We...

Cellular and Microbial In Vitro Modelling of Gastrointestinal Cancer.

Human diseases are multifaceted, starting with alterations at the cellular level, damaging organs and their functions, and disturbing interactions and immune responses. In vitro systems offer clarity and standardisation, which are crucial for effectively modelling disease. These models aim not to replicate every disease aspect but to dissect specific ones with precision. Controlled environments allow researchers to isolate key variables, eliminate confounding factors and elucidate disease mechanisms more clearly. Technological progress has rapidly advanced model systems. Initially, 2D cell culture models explored fundamental cell interactions. The transition to 3D cell cultures and organoids enabled more life-like tissue architecture and enhanced intercellular interactions. Advanced bioreactor-based devices now recreate the physicochemical environments of specific organs, simulating features like perfusion and the gastrointestinal tract's mucus layer, enhancing physiological relevance. These systems have been simplified and adapted for high-throughput research, marking significant progress. This review focuses on in vitro systems for modelling gastrointestinal tract cancer and the side effects of cancer treatment. While cell cultures and in vivo models are invaluable, our main emphasis is on bioreactor-based in vitro modelling systems that include the gut microbiome.

Tricholoma matsutake heptapeptide prevents gastric mucosa injury by regulating oxidative stress‐related mitochondrial function and mucous layer integrity

AbstractShort‐term excessive alcohol consumption easily leads to ethanolic gastric injury. Recent research on bioactive functional factors in preventing and treating ethanol‐induced acute gastric injury has garnered attention. This study explored the direct protective effects of the Tricholoma matsutake‐derived peptide Ser–Ala–Pro–Trp–Gly–Leu–Ala (SAPWGLA) on ethanol‐induced acute gastric damage. The results showed that SAPWGLA showed dose‐dependent protection against gastric mucosal injury, including the regulation of oxidative stress and mitochondrial function, as well as the enhancement of mucosal barrier integrity. SAPWGLA maintained normal mitochondrial metabolism by alleviating intracellular reactive oxygen species (ROS) accumulation; 400 mg/mL SAPWGLA reduced ROS levels by 81.72 ± 1.55% and reversed the decrease of MMP by ethanol to 1.22 ± 0.01 (J‐aggregates/monomer) in GES‐1 cells. Also, SAPWGLA enhanced the tight junctions between GES‐1 cells. In addition, SAPWGLA improved the integrity of the mucosal barrier by maintaining the balance of the mucus layer and regulating the expression of TJ proteins. Daily oral administration of SAPWGLA (50 mg/kg) exhibited a restoration in hexosamine to 10.76 ± 0.73 mg/g prot, a regulation in claudin‐1, occludin, and ZO‐1 (1.21‐, 1.39‐, and 0.73‐fold of the control group). These findings suggest that SAPWGLA can be a potential novel therapeutic approach to dealing with acute gastric injury caused by ethanol.

Orally Ingested Micro- and Nano-Plastics: A Hidden Driver of Inflammatory Bowel Disease and Colorectal Cancer.

Micro- and nano-plastics (MNPLs) can move along the food chain to higher-level organisms including humans. Three significant routes for MNPLs have been reported: ingestion, inhalation, and dermal contact. Accumulating evidence supports the intestinal toxicity of ingested MNPLs and their role as drivers for increased incidence of colorectal cancer (CRC) in high-risk populations such as inflammatory bowel disease (IBD) patients. However, the mechanisms are largely unknown. In this review, by using the leading scientific publication databases (Web of Science, Google Scholar, Scopus, PubMed, and ScienceDirect), we explored the possible effects and related mechanisms of MNPL exposure on the gut epithelium in healthy conditions and IBD patients. The summarized evidence supports the idea that oral MNPL exposure may contribute to intestinal epithelial damage, thus promoting and sustaining the chronic development of intestinal inflammation, mainly in high-risk populations such as IBD patients. Colonic mucus layer disruption may further facilitate MNPL passage into the bloodstream, thus contributing to the toxic effects of MNPLs on different organ systems and platelet activation, which may, in turn, contribute to the chronic development of inflammation and CRC development. Further exploration of this threat to human health is warranted to reduce potential adverse effects and CRC risk.

A Microphysiological System with an Anaerobic Air-Liquid Interface and Functional Mucus Layer for Coculture of Intestinal Bacteria and Primary Human Colonic Epithelium.

Coculture of intestinal bacteria with primary human intestinal epithelium provides a valuable tool for investigating host-colon bacterial interactions and for testing and screening therapeutics. However, most current intestinal model systems lack key physiological features of the in vivo colon, such as both a proper oxygen microenvironment and a mucus layer. In this work, a new in vitro colonic microphysiological system is demonstrated with a cell-derived, functional mucus that closely resembles the in vivo colonic mucosa and apical microenvironment by employing an anaerobic air-liquid interface culture. The human primary colon epithelial cells in this new in vitro system exhibit high cell viability (>98%) with ≈100 μm thick functional mucus layer on average. Successful coculture of model anaerobic gut bacterial strains Lactobacillus rhamnosus GG and Anaerobutyricum hallii without loss in human cell viability demonstrates that this new model can be an invaluable tool for future studies of the impact of commensal and pathogenic bacteria on the colon.