Mucosal bacterial microflora and mucus layer thickness in adolescents with inflammatory bowel disease

AIM:To assess the mucosa-associated bacterial microflora and mucus layer in adolescents with inflammatory bowel disease(IBD) .METHODS:Sixty-one adolescents(mean age 15 years,SD ± 4.13) were included in the study.Intestinal biopsies from inflamed and non-inflamed mucosa of IBD patients and from controls with functional abdominal pain were cultured under aerobic and anaerobic conditions.The number of microbes belonging to the same group was calculated per weight of collected tissue.The mucus thickness in frozen samples was measured under a fluorescent microscope.RESULTS:The ratios of different bacterial groups in inflamed and non-inflamed mucosa of IBD patients and controls were specific for particular diseases.Streptococcus spp.were predominant in the inflamed mucosa of Crohn's disease(CD) patients(80% of all bacteria) ,and Lactobacillus spp.were predominant in ulcerative colitis patients(90%) .The differences were statistically significant(P = 0.01-0.001) .Lower number of bifidobacteria was observed in the whole IBD group.A relation was also found between clinical and endoscopic severity and decreased numbers of Lactobacillus and,to a lesser extent,of Streptococcus in biopsies from CD patients.The mucus layer in the inflamed sites was significantly thinner as compared to controls(P = 0.0033) and to non-inflamed areas in IBD patients(P = 0.031) .CONCLUSION:The significantly thinner mucosa of IBD patients showed a predominance of some aerobes specific for particular diseases,their numbers decreased in relation to higher clinical and endoscopic activity of the disease.

Interaction between mucus layer and gut microbiota in non-alcoholic fatty liver disease:Soil and seeds

The intestinal mucus layer is a barrier that separates intestinal contents and epithelial cells,as well as acts as the"mucus layer-soil"for intestinal flora adhesion and colonization.Its structural and functional integrity is crucial to human health.Intestinal mucus is regulated by factors such as diet,living habits,hormones,neurotransmitters,cytokines,and intestinal flora.The mucus layer’s thickness,viscosity,porosity,growth rate,and glycosylation status affect the structure of the gut flora colonized on it.The interaction between"mucus layer-soil"and"gut bacteria-seed"is an important factor leading to the pathogenesis of non-alcoholic fatty liver disease(NAFLD).Probiotics,prebiotics,fecal microbiota transplantation(FMT),and wash microbial transplantation are efficient methods for managing NAFLD,but their long-term efficacy is poor.FMT is focused on achieving the goal of treating diseases by enhancing the"gut bacteria-seed".However,a lack of effective repair and management of the"mucus layer-soil"may be a reason why"seeds"cannot be well colonized and grow in the host gut,as the thinning and destruction of the"mucus layer-soil"is an early symptom of NAFLD.This review summarizes the existing correlation between intestinal mucus and gut microbiota,as well as the pathogenesis of NAFLD,and proposes a new perspective that"mucus layer-soil"restoration combined with"gut bacteria-seed"FMT may be one of the most effective future strategies for enhancing the long-term efficacy of NAFLD treatment.

Long-term exposure to titanium dioxide nanoparticles promotes diet-induced obesity through exacerbating intestinal mucus layer damage and microbiota dysbiosis

Titanium dioxide nanoparticles (TiO2-NPs) are commonly used as food additives, including some high-fat foods that are risk factors for obesity. However, little is known about the effects of chronic TiO2-NPs digestion in the population on high fat diet (HFD). Herein, we reported that TiO2-NPs exacerbated HFD-induced obesity by disruption of mucus layer and alterations of gut microbiota. Oral intake of TiO2-NPs significantly increased body weight, liver weight, and amount of adipose tissues, especially in HFD-fed mice. Mechanistic studies revealed TiO2-NPs induced colonic mucus layer disruption and obesity-related microbiota dysbiosis. The damage on mucus was demonstrated through down-regulation of Muc2 gene and the absorption of mucin protein by TiO2-NPs. Consequently, mucus layer damage combined microbiota dysbiosis escalated the low-grade systemic inflammation, which exacerbated HFD-induced obesity. In contrast, gut microbiota depletion eliminated these effects, indicating gut microbiota were necessary for TiO2-NPs-induced inflammation and obesity. All the results stated the alarming role of TiO2-NPs in the HFD-driven obesity and emphasized the reevaluating the health impacts of nanoparticles commonly used in daily life, particularly, in susceptible population.

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.

Rod-like mesoporous silica nanoparticles facilitate oral drug delivery via enhanced permeation and retention effect in mucus

The physiochemical characteristics of nanoparticles affect their in vitro and in vivo performance significantly,such as diameter,surface chemistry,and shape.This paper disclosed the effect of enhanced permeation and retention(EPR)in mucus caused by nanoparticle shape on improving oral absorption.The spherical and rod-like mesoporous silica nanoparticles(MSNs)were used to evaluate shape effect of EPR in mucus.Fenofibrate was loaded in MSNs as model drug.The in vitro release of fenofibrate from MSNs was dependent on nanoparticle shapes,but faster than that of raw drug.The drug release slowed down with the increase of aspect ratio due to longer channels in rod-like MSNs with higher aspect ratio.However,in vivo study showed that the oral bioavailability of fenofibrate was the highest after loading in rod-like MSNs with aspect ratio of 5.The in vitro study of mechanisms revealed that superior mucus diffusion ability of rod-like MSNs with aspect ratio of 5 was conductive to higher bioavailability.Meanwhile,more rod-like MSNs with higher aspect ratio were able to diffuse into mucus and reside there compared to spherical and short counterparts,which demonstrated higher aspect ratio was beneficial to EPR effect of nanoparticles in mucus.This study provides significant implication in rational oral drug carrier design.