Abelmoschus manihot polysaccharide fortifies intestinal mucus barrier to alleviate intestinal inflammation by modulating Akkermansia muciniphila abundance

The intestinal mucus barrier is an important line of defense against gut pathogens.Damage to this barrier brings bacteria into close contact with the epithelium,leading to intestinal inflammation.Therefore,its restoration is a promising strategy for alleviating intestinal inflammation.This study showed that Abelmoschus manihot polysaccharide(AMP)fortifies the intestinal mucus barrier by increasing mucus production,which plays a crucial role in the AMP-mediated amelioration of colitis.IL-10-deficient mouse models demonstrated that the effect of AMP on mucus production is dependent on IL-10.Moreover,bacterial depletion and replenishment confirmed that the effects of AMP on IL-10 secretion and mucus production were mediated by Akkermansia muciniphila.These findings suggest that plant polysaccharides fortify the intestinal mucus barrier by maintaining homeostasis in the gut microbiota.This demonstrates that targeting mucus barrier is a promising strategy for treating intestinal inflammation.

Damage on intestinal barrier function and microbial detoxification of deoxynivalenol:A review

Deoxynivalenol(DON)is a mycotoxin that is produced by various species of Fusarium and is ubiquitous in food and feed.At low concentrations,it can cause metabolic disorders in animals and humans and,at high concentrations,it can lead to pathological changes in the body.The impact of DON on human/animal health and animal productivity has thus attracted a great deal of attention around the world.DON causes severe damage to the intestine,including compromised intestinal barrier,mucosal damage,weakened immune function,and alterations in gut microbiota composition.These effects exacerbate intestinal infections and inflammation in livestock and poultry,posing adverse effects on overall health.Furthermore,research into biological methods for DON detoxification is a crucial avenue for future studies.This includes the utilization of adsorption,enzymatic degradation,and other biological approaches to mitigate DON's impact,offering new strategies for prevention and treatment of DON-induced diseases.Future research will focus on identifying highly efficient detoxifying microorganisms or enzymes to reduce DON levels in food and feed,thereby mitigating its risks to both animals and human health.

Developments of mucus penetrating nanoparticles

Mucus can effectively protect the exposed mucosal surfaces due to its adhesive and viscoelastic properties.Most foreign particulates are efficiently trapped in mucus layers via steric obstruction and adhesion.Trapped particles are typically removed from the mucosal tissue within seconds to a few hours depending on their location sites.This article focuses on describing the tenacious mucus barrier properties,the strategies to investigate the interaction of nanoparticles with the mucus as well as the novel developments of mucus penetrating nanoparticles.

Intestinal barrier in inflammatory bowel disease

A complex mucosal barrier protects as the first line of defense the surface of the healthy intestinal tract from adhesion and invasion by luminal microorganisms. In this review, we provide an overview about the major components of this protective system as for example an intact epithelium, the synthesis of various antimicrobial peptides (AMPs) and the formation of the mucus layer. We highlight the crucial importance of their correct functioning for the maintenance of a proper intestinal function and the prevention of dysbiosis and disease. Barrier disturbances including a defective production of AMPs, alterations in thickness or composition of the intestinal mucus layer, alterations of pattern-recognition receptors, defects in the process of autophagy as well as unresolved endoplasmic reticulum stress result in an inadequate host protection and are thought to play a crucial role in the pathogenesis of the inflammatory bowel diseases Crohn’s disease and ulcerative colitis.

Aquaporin-8 expression is reduced in ileum and induced in colon of patients with ulcerative colitis

AIM： To study susceptibility genes which may play a potential role in the pathogenesis and etiology of inflammatory bowel disease （IBD）. METHODS： To identify potential susceptibility genes we performed global gene expression profiling in patients with IBD and control specimens. For determination of an intrinsic gene expression profile in ulcerative colitis （UC） and Crohn＇s disease （CD） compared to normal subjects, mucosal biopsies of non-inflamed regions of the colon and the terminal ileum were subjected to DNA microarray analysis. Real-time RT-PCR and immunohistochemistry were used for verification of selected regulated candidate genes and a genetic analysis was performed. RESULTS： We could show that aquaporin-8 （AQP8） mRNA and protein levels were significantly increased in the colon of UC patients compared to controls. Genetic analysis of the six exons and the promoter region of AQPS, however, revealed no mutations or polymorphisms in IBD patients. CONCLUSION： Our results suggest that upregulation of AQP8 in the colon of UC patients represents a secondary phenomenon which may, due to altered water exchange of the distal intestinal mucosa, disturb the physiologic colonic mucus barrier and thus lead to chronic inflao mmation and ulceration.

Dietary sophorolipid accelerates growth by modulation of gut microbiota population and intestinal environments in broiler chickens

Background:Gut is a crucial organ for the host’s defense system due to its filtering action of the intestinal membrane from hazardous foreign substances.One strategy to strengthen the gut epithelial barrier function is to upregulate beneficial microflora populations and their metabolites.Sophorolipid(SPL),which is a glycolipid biosurfactant,could increase beneficial microflora and decrease pathogenic bacteria in the gastrointestinal tract.Therefore,herein,we conducted an experiment with broiler chickens to investigate the fortifying effects of SPL on the host’s gut defense system by modulating the microbiota population.Methods:A total of 5401-day-old chicks(Ross 308)were used,and they were immediately allotted into three treatment groups(6 replications with 30 chicks/pen)according to their initial body weight.The dietary treatments consisted of CON(basal diet),BAM(10 mg/kg bambermycin),and SPL(10 mg/kg SPL).During the experiment,birds freely accessed feed and water,and body weight and feed intake were measured at the end of each phase.On d 35,birds(one bird/pen)were sacrificed to collect jejunum and cecum samples.Results:Dietary SPL and BAM supplementation significantly accelerated birds’growth and also significantly improved feed efficiency compared to CON.Intestinal microbial community was significantly separated by dietary SPL supplementation from that of CON,and dietary SPL supplementation significantly increased Lactobacillus spp.and Akkermansia muciniphila.Moreover,birds fed with dietary SPL also showed the highest concentration of cecal butyrate among all treatment groups.Gut morphological analysis showed that dietary SPL significantly increased villus height,ratio of villus height to crypt depth,goblet cell numbers,and the gene expression levels of claudin-1 and mucin 2.Additionally,dietary SPL significantly decreased the mRNA expression level of pro-inflammatory cytokine,interleukin-6,and increased that of anti-inflammatory cytokine,interleukin-10,compared to other treatments.Conclusions:Dietary SPL increases the beneficial bacterial population and butyrate concentration,which leads to a strengthened gut barrier function.In addition,the intestinal inflammation was also downregulated by dietary SPL supplementation.

Increasing stiffness promotes pulmonary retention of ligand-directed dexamethasone-loaded nanoparticle for enhanced acute lung inflammation therapy

Inhaled nanoparticles(NPs)need to penetrate the bronchial mucosa to deliver drug payloads deeply in the lung for amplified local therapy.However,the bronchial mucociliary barrier eliminates NPs rapidly,which considerably limits their mucosal penetration.In this study,we find that surface ligand modification and stiffness adjustment of NPs contribute to the significantly enhanced bronchial mucosal absorption and pulmonary retention of inhaled drugs.We utilize neonatal Fc receptor ligand(FcBP)to modify the rationally designed low stiffness NPs(Soft-NP)and high stiffness NPs(Stiff-NP)to target bronchial mucosa.In an acute lung inflammation rat model,after intranasal administration with dexamethasone-loaded NPs,Stiff-NP endowed with FcBP displays superior therapeutic effects.The in vitro data demonstrate that the promotion effect of FcBP to bronchial mucosal absorption of Stiff-NP dominates over Soft-NP.This could be attributed to the higher affinity between ligand-receptor when incorporating FcBP on the Stiff-NP surface.Meanwhile,high stiffness modulates more actin filaments aggregation to mediate endocytosis,along with strengthened Ca2+signal to enhance exocytosis.Conclusively,we highlight that FcBP-modified NPs with higher stiffness would be a potential pulmonary drug delivery system.