Intestinal Mucus Research Articles

Interaction between soy hull polysaccharide and mucin with sodium-/potassium-ion treatment: interfacial property

Abstract The interaction between soy hull polysaccharide and intestinal mucus is influenced by different ions. This study investigates the effects of various concentrations of Na+/K+ on the stability, interfacial activity, and viscoelasticity of the microwave-assisted ammonium oxalate extraction of soy hull polysaccharide (MASP) in simulated intestinal fluids (SIFs) in terms of particle size, zeta potential, surface hydrophobicity, Fourier-transform infrared spectroscopy, shear rheology, and microstructure. Results showed that 1.5 % Na+/K+ causes MASP and mucin in SIFs to bind through physical adsorption; the average particle size of the MASP/SIF miscible system increases from 1,659 to 1,881 and 1,736 nm. When the ion strength is 0.5 %, MASP rapidly reduces the SIF interfacial tension. The addition of Na+/K+ causes a slight redshift in the protein amide I band and an increase in the α-helix content with respect to the decrease in the β-turn and β-sheet corner content. Furthermore, 0.5 % content of Na+ and K+ causes small MASP particles to adsorb onto the surface of mucin, while 1.5 % content of Na+ and K+ causes MASP particles to arrange above mucin after 12 h. These findings provide reference for a deeper understanding of the selection of macroelements (sodium and potassium) in the intake of polysaccharide.

In vitro and invivo investigation of the biological action of xylooligosaccharides derived from industrial waste.

Xylooligosaccharides (XOS) are prebiotics of significant biological value that can be obtained through cost-effective purification of agricultural waste. The present research featured invitro and invivo investigation of prebiotic effects of xylooligosaccharides derived from wheat bran powder and brewer's spent grain. Prebiotic activity of Lactobacillus. fermentum, Lactobacillus. casei, and Bifidobacterium spp. was investigated invitro using standard selective media. 16S rRNA quantitative PCR used for invitro and invivo investigation quantified relative abundance of Bifidobacterium spp., Lactobacillus spp., and Akkermansia. muciniphila in samples of fecal matter, cecal content, and intestinal tissue. Research revealed a favorable association between XOS concentration and both bacterial count and diameter of resultant colonies. The standard strain of L. casei showed no noticeable effect on growth rate. Bifidobacterium spp. proliferation in intestinal tissue was validated via invivo tests using XOS obtained from wheat bran powder and brewer's spent grain. Findings indicated increased prevalence of the A. muciniphila species and the presence of XOS showed a protective function in preserving the structural integrity of intestinal mucus secretions. The presence of XOS in food indicated direct association with proliferation of Bifidobacterium spp. and A. muciniphila spp. Study results suggest that XOS extracted through enzymatic hydrolysis in Mongolian food industry by-products such as wheat bran products and brewer's spent grain exhibit prebiotic properties that justify XOS manufacture on a large scale and incorporation of XOS as nutritional enhancement in food products and pharmaceuticals.

Synthesis of Thiomer/Nanoclay Nanocomposites as a Potential Drug Carrier: Evaluation of Mucoadhesive and Controlled Release Properties

Novel thiomer/nanoclay nanocomposites based on a thiomer and montmorillonite (MMT) were prepared in order to obtain a mucoadhesive material with controlled release properties for its potential use as drug carrier. The thiomer was synthesized by immobilization of L-cysteine in alginate mediated by carbodiimide reaction and further characterized by FT-IR and Ellman's reaction. Nanocomposites with growing concentrations of thiomer and MMT were prepared and analyzed by XRD, TGA and TEM. Rheological behavior of nanocomposite in contact with mucin and intestinal mucus were studied as in vitro and in situ mucoadhesion approach, showing until ∼10-fold increasing in the complex viscosity and ∼27-fold in elastic modulus when the amount of thiomer is increased. Higuchi and Korsmeyer-Peppas kinetic models were evaluated in order to study the release of deltamethrin from nanocomposite films. Release profiles showed a retard in the migration of the drug influenced by the amount of MMT (P < 0.05). Diffusion coefficient (D) showed a significant decrease (P < 0.0001) when concentration of MMT is increased reaching D = 4.18 × 10–7 m2 h–1, which resulted ∼7-fold lower in comparison with formulation without MMT. This hybrid nanocomposite can be projected as a potential mucoadhesive drug carrier with controlled release properties.

Ex-vivo investigation of probiotic bacterial adhesion to the intestinal mucus

Recent research has promoted considerable interest in the potential health benefits of the new generation of probiotics. Despite the abundance of probiotic supplements, their adhesion and thereby colonization in the intestinal tract of the host, a determining factor of probiotic efficacy, remains questionable. Indeed, the gastrointestinal tract, a multi-component and complex system, obscures the comprehensive understanding of the probiotic adhesion mechanism. This study aimed to investigate the adhesion capacity of probiotic bacteria using two ex-vivo approaches that were specifically developed to investigate the bacteria-mucus agglomeration and the viable adhesion to intestinal mucus. Five probiotic bacterial strains including Escherichia coli, Lactiplantibacillus plantarum, Faecalibacterium duncaniae, Bifidobacterium longum, and Bifidobacterium longum str. infantis were selected for the investigation. In that context, higher adhesion to mucus was demonstrated by E. coli, L. plantarum, and B. infantis, emphasizing strain-specific differences. While total agglomeration capacity ranged from 8 % to 82 %, actual viable adhesion to mucus remained rather low (0.6 %–2.9 %). SEM images revealed that morphological characteristics, chain and/or cluster forming ability, as well as the presence of surface exopolysaccharides, might have an impact on bacterial adhesion. This study contributes knowledge on probiotic adhesion as well as simple and effective ex-vivo approaches to investigate the bacterial adhesion to the intestinal mucus, which is prerequisite for further colonization in the gut of the host.

Mini-colons predict drug toxicity in vitro

Mitrofanova etal.1 engineer a human colonic invitro model capable of producing an intestinal mucus barrier, with potential applications for predicting drug-induced gastrointestinal toxicity. This improved system paves the way for more accurate and efficient drug development processes.

Effects of a multi-strain Bacillus probiotic on the intestinal microbiome, haemato-immunology, and growth performance of Nile tilapia.

The study evaluated dietary supplementation with a feed additive composed of multi-strain Bacillus for Nile tilapia Oreochromis niloticus. In vitro and in vivo assays employing culture-based microbiological methods and metagenomics were performed. Additionally, the study assessed the haemato-immunology, intestinal microbiome, and growth performance of the animals. For this, 30 juvenile Nile tilapia were used in the in vitro assay and 180 (60 + 120) in the in vivo assays. In the in vitro assay, we found evidence of adhesion of the probiotic bacteria to the intestinal mucus of fish, corroborated in the 15-day in vivo assay, in which the count of B. licheniformis was significantly higher in fish fed with probiotic when compared to fish of the control group. Furthermore, in the 50-day in vivo trial, a metagenomic analysis provided evidence for the modulation of the intestine microbiome of Nile tilapia by dietary supplementation of the probiotic. In addition, there was an increase in species richness, higher abundance of potentially probiotic autochthonous species and a lower abundance of Aeromonas sp. when the animals were fed the supplemented diet. Finally, no significant differences were observed in growth performance and haemato-immunological analyses, suggesting no harm to fish health when the product was supplemented for 15 and 50 days. The in vitro results indicate that the multi-strain probiotics were able to adhere to the intestinal mucus of Nile tilapia. Additionally, a modulation of the intestinal microbiome was evidenced in the in vivo assay.

Assessing the presence of microplastic in agriculture soils irrigated with treated waste waters using Lumbricus sp.: Ecotoxicological effects

Global water scarcity entailed the use of treated wastewater (TWW) in agriculture, however, this water can vehiculate numerous pollutants into soil and further crops such as microplastics (MPs). To date, few studies had quantified the accumulation of MPs in soils and earthworms after irrigation with TWW as well as their toxicological effects. Hence, the main objective of the present work is to evaluate the toxicity of MPs using Lumbricus sp. earthworms collected from TWW irrigated soils with an increasing gradient of time (5 years, 16 years and 24 years). MPs determination in soil, as well as in earthworms were performed. The intestinal mucus was quantified, and cytotoxicity (Lysosomal membrane stability (LMS), Catalase (CAT) and glutathione-S-Transferase (GST) activities), neurotoxicity (Acetylcholinesterase activity (AChE)) and genotoxicity (Micronuclei frequency (MNi)) biomarker were assessed. Our results revealed that the use of TWW rendered MPs accumulation in earthworms' tissues and induce alteration on the intestinal mucus. An important cytotoxicity time-depending was observed being associated with an increase on genotoxicity. Overall, the present investigation highlights the ecotoxicological risk associated with the use of TWWs as an important driver of MPs and consequently measures are necessary to reduce MPs in wastewater treatment plans to improve this non-conventional water quality.

Thiolated nanoclays as a potential mucoadhesive material: Optimization by design of experiments and multivariate regression

An integrated strategy based on design of experiments (DoE) and multivariate regression was carried out to produce an optimized surface functionalized nanoclay (Mt–SH) with potential mucoadhesive properties. A mercaptosilane was grafted in montmorillonite in order to immobilize thiol groups (–SH) on the clay. The functionalization was confirmed by IR, TGA, XRF and XRD analyses. Five variables involved in the synthesis were optimized in order to maximize two responses: mass of functionalized nanoclay and amount of thiol groups attached in the clay surface. This optimization was performed by a two–step DoE strategy using Plackett–Burman and Box–Behnken designs. The five variables and two responses were simultaneously calibrated in a single ANOVA–validated PLS regression model. Analyzing scores, loading and surface response plots, the main processing variables, interactions and quadratic terms were found achieving the optimal processing conditions for the synthesis. The quadratic model (R2 > 0.8589) predicted an optimized functionalized nanoclay of mass 3.29 ± 0.13 g of Mt–SH with 19.65 ± 0.78 μmol –SH per g Mt–SH (P < 0.05). The optimized Mt–SH was evaluated by in vitro and in situ mucoadhesion assays with porcine mucin and fresh intestinal mucus by using rheometry. The complex viscosity showed an increase of ∼54-fold higher compared to the unmodified Mt, and ∼12.8-fold increase in the elastic modulus, which indicates a more resistance to elastic deformation probably due to an increase in cross-linking points between Mt–SH and mucus. The formation of disulfide bonds between thiol groups from Mt–SH and glycoproteins in the mucin could be a reasonably explanation which shows a correlation respect other thiolated materials which show the same mucoadhesion properties. These results could project this functionalized silicate material as a potential mucoadhesive prospect for pharmaceutical applications.

A history of repeated antibiotic usage leads to microbiota-dependent mucus defects

ABSTRACT Recent evidence indicates that repeated antibiotic usage lowers microbial diversity and ultimately changes the gut microbiota community. However, the physiological effects of repeated – but not recent – antibiotic usage on microbiota-mediated mucosal barrier function are largely unknown. By selecting human individuals from the deeply phenotyped Estonian Microbiome Cohort (EstMB), we here utilized human-to-mouse fecal microbiota transplantation to explore long-term impacts of repeated antibiotic use on intestinal mucus function. While a healthy mucus layer protects the intestinal epithelium against infection and inflammation, using ex vivo mucus function analyses of viable colonic tissue explants, we show that microbiota from humans with a history of repeated antibiotic use causes reduced mucus growth rate and increased mucus penetrability compared to healthy controls in the transplanted mice. Moreover, shotgun metagenomic sequencing identified a significantly altered microbiota composition in the antibiotic-shaped microbial community, with known mucus-utilizing bacteria, including Akkermansia muciniphila and Bacteroides fragilis, dominating in the gut. The altered microbiota composition was further characterized by a distinct metabolite profile, which may be caused by differential mucus degradation capacity. Consequently, our proof-of-concept study suggests that long-term antibiotic use in humans can result in an altered microbial community that has reduced capacity to maintain proper mucus function in the gut.

Analysis of Neuropeptides in the Intestinal Mucus of Patients with Ulcerative Colitis Using RNA Sequencing

Introduction: Inflammation in ulcerative colitis (UC) originates in the colorectal mucosa. Transcriptome sequencing analysis of the colorectal mucosa allows the identification of potential neuropeptides related to local neurotransmission. The intestinal mucus lining the surface of the mucosa may harbor biomarkers of mucosal inflammation; however, this has not been sufficiently investigated, given the difficulty in obtaining human samples. We previously reported the feasibility of obtaining mucin samples for proteomic analysis by brushing during colonoscopy. Herein, we aimed to investigate the composition of the intestinal mucus and detect neuropeptides characteristic of UC. Methods: Mucus and mucosal samples were collected from patients with UC from the colorectum in areas showing remission or active UC using a brush catheter and biopsy forceps during colonoscopy. RNA sequencing findings of mucus samples of active and remission areas were compared. RNA and protein expression levels of significantly upregulated neuropeptides were analyzed. Results: Of the neuropeptides associated with UC, somatostatin (SST) was significantly elevated in areas of remission, according to RNA sequencing results of mucus and expression levels in mucus RNA and proteins. Conversely, SST expression in the mucosa was increased in the inflamed areas. Flow cytometry revealed that the fluorescence intensity of SST-positive cells in the remission zone was higher in the mucus than in the mucosa. Conclusion: SST expression in the mucus is considered to be an important factor associated with UC activity.

B3galt5 functions as a PXR target gene and regulates obesity and insulin resistance by maintaining intestinal integrity

Pregnane X receptor (PXR) has been reported to regulate glycolipid metabolism. The dysfunction of intestinal barrier contributes to metabolic disorders. However, the role of intestinal PXR in metabolic diseases remains largely unknown. Here, we show that activation of PXR by tributyl citrate (TBC), an intestinal-selective PXR agonist, improves high fat diet (HFD)-induced obesity. The metabolic benefit of intestinal PXR activation is associated with upregulation of β-1,3 galactosyltransferase 5 (B3galt5). Our results reveal that B3galt5 mainly expresses in the intestine and is a direct PXR transcriptional target. B3galt5 knockout exacerbates HFD-induced obesity, insulin resistance and inflammation. Mechanistically, B3galt5 is essential to maintain the integrity of intestinal mucus barrier. B3galt5 ablation impairs the O-glycosylation of mucin2, destabilizes the mucus layer, and increases intestinal permeability. Furthermore, B3galt5 deficiency abolishes the beneficial effect of intestinal PXR activation on metabolic disorders. Our results suggest the intestinal-selective PXR activation regulates B3galt5 expression and maintains metabolic homeostasis, making it a potential therapeutic strategy in obesity.

Urolithin A-mediated augmentation of intestinal barrier function through elevated secretory mucin synthesis

Maintaining the mucus layer is crucial for the innate immune system. Urolithin A (Uro A) is a gut microbiota-derived metabolite; however, its effect on mucin production as a physical barrier remains unclear. This study aimed to elucidate the protective effects of Uro A on mucin production in the colon. In vivo experiments employing wild-type mice, NF-E2-related factor 2 (Nrf2)-deficient mice, and wild-type mice treated with an aryl hydrocarbon receptor (AhR) antagonist were conducted to investigate the physiological role of Uro A. Additionally, in vitro assays using mucin-producing cells (LS174T) were conducted to assess mucus production following Uro A treatment. We found that Uro A thickened murine colonic mucus via enhanced mucin 2 expression facilitated by Nrf2 and AhR signaling without altering tight junctions. Uro A reduced mucosal permeability in fluorescein isothiocyanate-dextran experiments and alleviated dextran sulfate sodium-induced colitis. Uro A treatment increased short-chain fatty acid-producing bacteria and propionic acid concentration. LS174T cell studies confirmed that Uro A promotes mucus production through the AhR and Nrf2 pathways. In conclusion, the enhanced intestinal mucus secretion induced by Uro A is mediated through the actions of Nrf-2 and AhR, which help maintain intestinal barrier function.

Disruption of intestinal oxygen balance in acute colitis alters the gut microbiome

ABSTRACT The juxtaposition of well-oxygenated intestinal colonic tissue with an anerobic luminal environment supports a fundamentally important relationship that is altered in the setting of intestinal injury, a process likely to be relevant to diseases such as inflammatory bowel disease. Herein, using two-color phosphorometry to non-invasively quantify both intestinal tissue and luminal oxygenation in real time, we show that intestinal injury induced by DSS colitis reduces intestinal tissue oxygenation in a spatially defined manner and increases the flux of oxygen from the tissue into the gut lumen. By characterizing the composition of the microbiome in both DSS colitis-affected gut and in a bioreactor containing a stable human fecal community exposed to microaerobic conditions, we provide evidence that the increased flux of oxygen into the gut lumen augments glycan degrading bacterial taxa rich in glycoside hydrolases which are known to inhabit gut mucosal surface. Continued disruption of the intestinal mucus barrier through such a mechanism may play a role in the perpetuation of the intestinal inflammatory process.

Revealing Glycosylation Patterns in In Vitro-Produced Mucus Exposed to Pasteurized Mucus-Associated Intestinal Microbes by MALDI-TOF-MS and PGC-LC-MS/MS.

The human intestinal mucus layer protects against pathogenic microorganisms and harmful substances, whereas it also provides an important colonization niche for mutualistic microbes. The main functional components of mucus are heavily glycosylated proteins, called mucins. Mucins can be cleaved and utilized by intestinal microbes. The mechanisms between intestinal microbes and the regulation of mucin glycosylation are still poorly understood. In this study, in vitro mucus was produced by HT29-MTX-E12 cells under Semi-Wet interface with Mechanical Stimulation. Cells were exposed to pasteurized nonpathogenic bacteria Akkermansia muciniphila, Ruminococcus gnavus, and Bacteroides fragilis to evaluate influence on glycosylation patterns. Following an optimized protocol, O- and N-glycans were efficiently and reproducibly released, identified, and semiquantified using MALDI-TOF-MS and PGC-LC-MS/MS. Exposure of cells to bacteria demonstrated increased diversity of sialylated O-glycans and increased abundance of high mannose N-glycans in in vitro produced mucus. Furthermore, changes in glycan ratios were observed. It is speculated that bacterial components interact with the enzymatic processes in glycan production and that pasteurized bacteria influence glycosyltransferases or genes involved. These results highlight the influence of pasteurized bacteria on glycosylation patterns, stress the intrinsic relationship between glycosylation and microbiota, and show the potential of using in vitro produced mucus to study glycosylation behavior.

Cy3-Based Nanoviscosity Determination of Mucus: Effect of Mucus Collection Methods and Antibiotics Treatment.

The integrity of the protective mucus layer as a primary defense against pathogen invasion and microbial leakage into the intestinal epithelium can be compromised by the effects of antibiotics on the commensal microbiome. Changes in mucus integrity directly affect the solvent viscosity in the immediate vicinity of the mucin network, that is, the nanoviscosity, which in turn affects both biochemical reactions and selective transport. To assess mucus nanoviscosity, a reliable readout via the viscosity-dependent fluorescence lifetime of the molecular rotor dye cyanine 3 is established and nanoviscosities from porcine and murine ex vivo mucus are determined. To account for different mucin concentrations due to the removal of digestive residues during mucus collection, the power law dependence of mucin concentration on viscosity is used. The impact of antibiotics combinations (meropenem/vancomycin, gentamycin/ampicillin) on ex vivo intestinal mucus nanoviscosity is presented. The significant increase in viscosity of murine intestinal mucus after treatment suggests an effect of antibiotics on the microbiota that affects mucus integrity. This method will be a useful tool to assess how drugs, directly or indirectly, affect mucus integrity. Additionally, the method can be utilized to analyze the role of mucus nanoviscosity in health and disease, as well as in drug development.

Hydrogel-Integrated Millifluidic Systems: Advancing the Fabrication of Mucus-Producing Human Intestinal Models.

The luminal surface of the intestinal epithelium is protected by a vital mucus layer, which is essential for lubrication, hydration, and fostering symbiotic bacterial relationships. Replicating and studying this complex mucus structure in vitro presents considerable challenges. To address this, we developed a hydrogel-integrated millifluidic tissue chamber capable of applying precise apical shear stress to intestinal models cultured on flat or 3D structured hydrogel scaffolds with adjustable stiffness. The chamber is designed to accommodate nine hydrogel scaffolds, 3D-printed as flat disks with a storage modulus matching the physiological range of intestinal tissue stiffness (~3.7 kPa) from bioactive decellularized and methacrylated small intestinal submucosa (dSIS-MA). Computational fluid dynamics simulations were conducted to confirm a laminar flow profile for both flat and 3D villi-comprising scaffolds in the physiologically relevant regime. The system was initially validated with HT29-MTX seeded hydrogel scaffolds, demonstrating accelerated differentiation, increased mucus production, and enhanced 3D organization under shear stress. These characteristic intestinal tissue features are essential for advanced in vitro models as they critically contribute to a functional barrier. Subsequently, the chamber was challenged with human intestinal stem cells (ISCs) from the terminal ileum. Our findings indicate that biomimicking hydrogel scaffolds, in combination with physiological shear stress, promote multi-lineage differentiation, as evidenced by a gene and protein expression analysis of basic markers and the 3D structural organization of ISCs in the absence of chemical differentiation triggers. The quantitative analysis of the alkaline phosphatase (ALP) activity and secreted mucus demonstrates the functional differentiation of the cells into enterocyte and goblet cell lineages. The millifluidic system, which has been developed and optimized for performance and cost efficiency, enables the creation and modulation of advanced intestinal models under biomimicking conditions, including tunable matrix stiffness and varying fluid shear stresses. Moreover, the readily accessible and scalable mucus-producing cellular tissue models permit comprehensive mucus analysis and the investigation of pathogen interactions and penetration, thereby offering the potential to advance our understanding of intestinal mucus in health and disease.

A novel function of benzoic acid to enhance intestinal barrier defense against PEDV infection in Piglets

The intestinal barrier of newborn piglets is vulnerable and underdeveloped, making them susceptible to enteric virus infections. Benzoic acid (BA), employed as a growth promoter, exhibits the potential to enhance the gut health of piglets by modulating intestinal morphometry and tight junction dynamics. However, the extent to which BA regulates the intestinal mucus barrier through its impact on stem cells remains inadequately elucidated. Therefore, this study was conducted to investigate the effects of BA on the intestinal barrier and the differentiation of intestinal stem cells, employing in vivo piglet and in vitro intestinal organoid models. Our investigation revealed a significant increase in the number of goblet cells within the small intestine, as well as the strengthening of the mucus barrier in vivo following oral treatment with BA, providing partial protection against PEDV infection in piglets. Additionally, in vitro cultivation of enteroids with BA led to a notable increase in the number of MUC2+ GCs, indicating the promotion of GC differentiation by BA. Furthermore, transcriptome analysis revealed an upregulation of the number of GCs and the expression of cell vesicle transport-related genes during BA stimulation, accompanied by the downregulation of the Wnt and Notch signaling pathways. Mechanistically, MCT1 facilitated the transport of BA, subsequently activating the MAPK pathway to mediate GC differentiation. Overall, this study highlights a novel function for BA as a feed additive in enhancing the intestinal mucus barrier by promoting intestinal GC differentiation, and further prevents viral infection in piglets.

Acesulfame potassium triggers inflammatory bowel disease via the inhibition of focal adhesion pathway

Acesulfame potassium (ACK) was generally regarded as innocuous and extensively ingested. Nevertheless, ACK has recently gained attention as a burgeoning pollutant that has the potential to induce a range of health hazards, particularly to the digestive system. Herein, we uncover that ACK initiates inflammatory bowel disease (IBD) in mice and zebrafish, as indicated by the aggregation of macrophages in the intestine and the inhibition of intestinal mucus secretion. Transcriptome analysis of mice and zebrafish guts revealed that exposure to ACK typically impacts the cell cycle, focal adhesion, and PI3K-Akt signaling pathways. Using pharmacological approaches, we demonstrate that the PI3K-Akt signaling pathway and the generation of reactive oxygen species (ROS) triggered by cell division are not significant factors in the initiation of IBD caused by ACK. Remarkably, inhibition of the focal adhesion pathway is responsible for the IBD onset induced by ACK. Our results indicate the detrimental impacts and possible underlying mechanisms of ACK on the gastrointestinal system and provide insights for making informed choices about everyday dietary habits.

The MUC2 Gene Product: Polymerisation and Post-Secretory Organisation-Current Models.

MUC2 mucin, the primary gel-forming component of intestinal mucus, is well researched and a model of polymerisation and post-secretory organisation has been published previously. Recently, several significant developments have been made which either introduce new ideas or challenge previous theories. New ideas include an overhaul of the MUC2 C-terminal globular structure which is proposed to harbour several previously unobserved domains, and include a site for an extra intermolecular disulphide bridge dimer between the cysteine 4379 of adjacent MUC2 C-termini. MUC2 polymers are also now thought to be secreted attached to the epithelial surface of goblet cells in the small intestine and removed following secretion via a metalloprotease meprin β-mediated cleavage of the von Willebrand D2 domain of the N-terminus. It remains unclear whether MUC2 forms intermolecular dimers, trimers, or both, at the N-termini during polymerisation, with several articles supporting either trimer or dimer formation. The presence of a firm inner mucus layer in the small intestine is similarly unclear. Considering this recent research, this review proposes an update to the previous model of MUC2 polymerisation and secretion, considers conflicting theories and data, and highlights the importance of this research to the understanding of MUC2 mucus layers in health and disease.

Oligomeric proanthocyanidins mitigate acute lung injury by inhibiting NETs and inflammation via the gut-lung axis

Acute lung injury is a common complication of sepsis and characterized by a high mortality rate during hospitalization. Proanthocyanidin, which are abundant compounds found in various plants, have shown promising effects in preventing chronic diseases, and their oligomers have attracted attention for their high bioavailability and strong antioxidant activity. In recent years, there have been suggestions that oligomeric proanthocyanidin may possess lung-protective properties, however, the specific mechanisms involved have not been fully elucidated. This study reveals that the therapeutic efficacy of oligomeric proanthocyanidin in mitigating lung injury during sepsis, achieved through the reduction of neutrophil extracellular traps accumulation and the attenuation of inflammation, can be attributed to the capacity to safeguard the integrity of the intestinal mucus layer and the intestinal barrier. This protective action results in a decrease in endotoxin entry into the bloodstream and bacterial translocation, both of which can trigger neutrophil extracellular traps causing further lung injury.