Intestinal Mucosal Immune Barrier Research Articles

Intestinal Mucosal Immune Barrier: A Powerful Firewall Against Severe Acute Pancreatitis-Associated Acute Lung Injury via the Gut-Lung Axis.

The pathogenesis of severe acute pancreatitis-associated acute lung injury (SAP-ALI), which is the leading cause of mortality among hospitalized patients in the intensive care unit, remains incompletely elucidated. The intestinal mucosal immune barrier is a crucial component of the intestinal epithelial barrier, and its aberrant activation contributes to the induction of sustained pro-inflammatory immune responses, paradoxical intercellular communication, and bacterial translocation. In this review, we firstly provide a comprehensive overview of the composition of the intestinal mucosal immune barrier and its pivotal roles in the pathogenesis of SAP-ALI. Secondly, the mechanisms of its crosstalk with gut microbiota, which is called gut-lung axis, and its effect on SAP-ALI were summarized. Finally, a number of drugs that could enhance the intestinal mucosal immune barrier and exhibit potential anti-SAP-ALI activities were presented, including probiotics, glutamine, enteral nutrition, and traditional Chinese medicine (TCM). The aim is to offer a theoretical framework based on the perspective of the intestinal mucosal immune barrier to protect against SAP-ALI.

Xixin Decoction regulates Th17/Treg balance and transcription factor expression in senescence-accelerated mouse-prone

This study aims to investigate the effect of Xixin Decoction on the T helper 17 cell(Th17)/regulatory T cell(Treg) ba-lance of intestinal mucosa and the expression of related transcription factors in the senescence-accelerated mouse-prone 8(SAMP8) model. Fifty 14-week male mice of SAMP8 were randomized by the random number table method into model group, probiotics group, and high-, medium-, and low-dose Xixin Decoction groups, with 10 mice in each group. Ten 14-week male mice of senescence-acce-lerated mouse-resistant 1(SAMR1) served as control group. After 10 weeks of feeding, the mice were administrated with correspon-ding drugs for 10 weeks. Morris water maze test was carried out to examine the learning and memory abilities of mice. Enzyme-linked immunosorbent assay(ELISA) was employed to determine the content of secretory immunoglobulin A(SIgA) in the intestinal mucosa, and flow cytometry to detect the percentage content of Th17 and Treg in the intestinal mucosa. Western blot was performed to determine the protein levels of retinoid-related orphan receptor gamma t(RORγt) and forkhead box p3(Foxp3) in the mouse colon tissue. Compared with control group, the escape latency of mice in model group was significantly prolonged(P<0.01), and the number of times of crossing the platform and the residence time in the target quadrant were significantly reduced within 60 s(P<0.01), intestinal mucosal SIgA content was significantly decreased(P<0.01), Th17 content was increased(P<0.05), Treg content was decreased(P<0.01), the expression of RORγt protein was increased and Foxp3 protein was decreased in colon(P<0.01). Compared with the model group, high-dose Xixin Decoction group improved the learning and memory ability(P<0.05 or P<0.01). Probiotics group and high-and medium-dose Xixin Decoction group increased the content of SIgA in intestinal mucosa(P<0.05 or P<0.01), decreased percentage content of Th17 and increased the percentage content of Treg in intestinal mucosa(P<0.05 or P<0.01). Furthermore, they down-regulated the protein level of RORγt and up-regulated the protein level of Foxp3 in the intestinal mucosa(P<0.01). In conclusion, Xixin Decoction may act on intestinal mucosal immune barrier, affect gut-brain information exchange, and improve the learning and memory ability of SAMP8 by promoting SIgA secretion and regulating the Th17/Treg balance and the expression of RORγt and Foxp3.

Disruption of the Intestinal Mucosal Barrier Induced by High Fructose and Restraint Stress Is Regulated by the Intestinal Microbiota and Microbiota Metabolites.

Environmental (restraint stress) and dietary (high fructose) factors are key triggers for flares of inflammatory bowel disease; however, the mechanisms involved in this phenomenon are not fully elucidated. This study aimed to investigate the mechanisms by which restraint stress and high fructose damage the intestinal mucosal immune barrier. The feces of C57BL/6J mice were subjected to 16S rRNA and untargeted metabolome sequencing, and the intestinal histological structure was analyzed by immunohistochemistry and immunofluorescence staining. The mRNA and protein levels of the intestinal protein were analyzed by reverse transcription-PCR (RT-PCR), Western blotting, and enzyme-linked immunosorbent assay (ELISA). The metabolites of the microbiota were tested in vitro, and Akkermansia muciniphila was used for colonization in vivo. Dietary fructose exacerbated the development of restraint stress, with an extensive change in the composition of the gut microbiota and microbial metabolites. The disturbance of the microbiota composition led to an increase in the abundance of histamine and a decrease in the abundance of taurine, which inhibited the expression of tight junction and MUC2 proteins, destroyed the function of NLRP6, and reduced intestinal autophagy level; this in turn disrupted the function of colonic goblet cells to secrete mucus, leading to defects in the intestinal mucosal barrier, which ultimately codrives colon autoinflammation. However, A. muciniphila supplementation counteracted damage to the intestinal mucosal barrier by high fructose and restraint stress. Therefore, the gut microbiota and microbiota metabolites play an important role in maintaining microenvironment homeostasis of the intestinal mucosal barrier. IMPORTANCE A high-fructose diet aggravated restraint stress-induced changes in the composition of the intestinal microbiome, in which the abundance of A. muciniphila was significantly increased. The high-fructose diet exacerbated restraint stress-induced the changes in the composition of the microbial metabolites, with taurine abundance being downregulated and histamine abundance upregulated. High fructose and restraint stress induced colonic mucosal immune barrier damage, possibly due to changes in the abundance of the microbial metabolites taurine and histamine. Colonization with A. muciniphila stimulated the expression of the NLRP6 inflammasome and activated autophagy in goblet cells, thereby producing more new mucins, which could protect the intestinal mucosal barrier.

Distribution of intraepithelial lymphocytes, mast cells, and goblet cells in the intestine of alpaca.

Intestinal diseases in ruminants are frequent and susceptible to invasion by exogenous substances, and the intestinal mucosal barrier is the first line of defence of the body's immune defence. At present, the study on the structure of intestinal mucosal immune barrier in alpaca is incomplete. Therefore, the alpaca intestines were studied to show the distribution characteristics of intestinal mucosal barrier structure and cells associated with immune system using histology, histochemistry, and immunohistochemistry. The results showed that the intestinal tract of alpaca was composed of mucosa, submucosa, muscularis, and serosa. Intraepithelial lymphocytes were distributed in mucosal epithelium and glands of the large intestine. Mast cells were distributed in each segment of the intestine, mainly in the intestinal lamina propria, intestinal glands, and duodenal glands around, as well as in the muscularis, and the particles of cytoplasm were obvious. Acidic goblet cells were mainly distributed in the ileal mucosal epithelium and ileal intestinal glands, while sialomucins were mainly expressed in the colon. The cells associated with the immune system in the intestinal mucosa of alpaca play an important role in protecting against foreign microbial invasion and infection, and this result provides a theoretical basis for revealing the occurrence of gastrointestinal diseases in alpaca.

Electroacupuncture at "Zusanli"(ST36) protects intestinal mucosal immune barrier by suppre-ssing apoptosis of intestinal lymphocytes and regulating expression of Bcl-2 and Bax in sepsis rats

To observe the effect of electroacupuncture (EA) at "Zusanli" (ST36) on apoptosis of intestinal T lymphocytes, translocation of intestinal bacteria and expression of intestinal Bcl-2 and Bax proteins and intestinal mucosal immune barrier in sepsis rats, so as to explore its underlying mechanism in relieving sepsis. SD rats were randomly divided into sham operation (n=6), model (n=15), non-meridian and non-acupoint (non-acupoint, n=15) and acupoint EA(n=15) groups by using random number table method. The sepsis model was established by using cecal ligation and perforation(CLP) method. EA (2 Hz, 2 mA) was applied to bilateral ST36 or non-acupoint for 30 min one hour after modeling, once every day for 3 days. The rats' general conditions and fatality rate in 3 days after modeling were recorded. The liver, spleen and mesenteric lymph nodes were taken for bacterial culture to detect the translocation rate of intestinal bacteria. The small intestinal tissue was taken for observing histopathological changes (Chiu's score: 0-5 points) after HE staining, and for determining the expression levels of Bcl-2 and Bax proteins using Western blot. The intestinal mucosa was sampled for detecting the apop-tosis (apoptotic index) of lymphocytes by using terminal deoxynucleoitidyl transferase-mediated deoxyuridine triphosphate biotin nick end labeling (TUNEL) assay, and the counts of CD4+ and CD8+T cells using flow cytometry. The contents of IL-4 in the small intestine and that of secretory IgA (sIgA) in the small intestinal mucus were determined by using ELISA. After modeling, of the 15 rats in each of the 3 groups, 7, 7 and 2 in the model, non-acupoint and EA groups were dead in the first 3 days, with the fatality rate being 46.67% (7/15), 46.67% (7/15) and 13.33% (2/15), respectively (being obviously lower in the EA group than in the former two groups, P<0.05). Compared with the sham operation group, the incidence of intestinal bacterial translocation, apoptotic index, Chiu's score, and Bax expression were significantly increased (P<0.05), and the percentages of CD4+ and CD8+T cells, IL-4 and sIgA contents and Bcl-2 expression considerably decreased (P<0.05) in the model group. In comparison with the model group, modeling-induced increase of incidence of bacterial translocation, apoptotic index and Bax expression, and decrease of percentages of CD4+ and CD8+T cells, IL-4 and sIgA contents and Bcl-2 expression were reversed (P<0.05) in the EA group. EA at ST36 can reduce death rate and intestinal bacteria translocation incidence in sepsis rats, which may be related to its functions in regulating the expression of intestinal Bcl-2 and Bax proteins and inhibiting the apoptosis of intestinal mucosal T lymphocytes, thereby protecting the immune barrier function of intestinal mucosa to reduce the intestinal permeability.

Herb Formula (GCis) Prevents Pulmonary Infection Secondary to Intracerebral Hemorrhage by Enhancing Peripheral Immunity and Intestinal Mucosal Immune Barrier.

Lung infection is a common complication induced by stroke and seriously affects the prognosis and life quality of patients. However, effective therapeutic strategies are still lacking. In the present study, the herb formula GCis was confirmed to prevent pulmonary infection induced by intracerebral hemorrhage (ICH). The animal model of lung infection induced by ICH, GCis (Ginseng Radix et Rhizoma, Aconiti Lateralis Radix Praeparata, and Cistanches Herba) was orally administrated every day for 7 days. Lung microbial biomass and pathological results showed that the GCis formula pretreatment significantly reduced lung bacterial biomass and alleviated pathological abnormalities. These results indicated that the GCis formula has a clear pharmacological effect on preventing lung infection induced by ICH. Immunosuppression induced by ICH seemed to be the main mechanism of lung infection. Our results showed that the spleen and thymus indexes, WBC, and LY% contents were significantly increased in the GCis formula group. Moreover, bone marrow cells were further analyzed by transcriptome sequencing, and GO and KEGG enrichment analysis results showed that immune function was the main pathway enriched by differential genes after GCis formula intervention. More importantly, our results showed that GCis pretreatment had no significant effect on the mRNA expression of IL-1β, IL-6, and TNF-α in the brain. These results indicated that the GCis formula could enhance immunity after ICH. The intestinal barrier function was further investigated in the present study, considering the origin of the source of infection. Our results showed that the mRNA expressions of intestinal ZO-1, SIgA, and MUC2 were significantly increased, villi structure was intact, inflammatory cell infiltration was reduced, and goblet cell number was increased after GCis formula treatment. These results suggest that the GCis formula can enhance the intestinal mucosal immune barrier. This study provides a herb formula (GCis) that could enhance peripheral immunity and intestinal mucosal immune barrier to prevent pulmonary infection induced by ICH. It would be beneficial in the prevention of severe clinical infections.

Moniezia benedeni Infection Restrain IgA+, IgG+, and IgM+ Cells Residence in Sheep (Ovis aries) Small Intestine

Secreted immunoglobulin A (SIgA), IgG, and IgM play a crucial role in forming the intestinal mucosal immune barrier, and parasites could disturb the host's immune response by releasing various immunomodulatory molecules. Moniezia benedeni is an important pathogen parasitizing in the sheep small intestine. It is aimed to explore the residence characteristics of IgA+, IgG+, and IgM+ cells in the sheep small intestine, and the influence of Moniezia benedeni infection on them. Control group (n = 6) and infected group (n = 6) were selected, respectively, and the three subtype cells residing in the small intestine were systematically observed and analyzed. The results showed that in the Control group, the three types of positive cells were all distributed diffusely, and the total densities in jejunum, duodenum and ileum was gradually declined in turn. Notably, the change trend of IgA+ and IgG+ cells densities were both congruent with the total densities, and the differences among them were significant, respectively (P < 0.05); the IgM+ cells density was the highest in duodenum, followed by jejunum and ileum, there was no significant difference between duodenum and jejunum (P > 0.05), but both significantly higher than in ileum (P < 0.05). In the Infected group, their total densities in duodenum, jejunum and ileum were gradually declined in turn. Notably, the IgA+ and IgM+ cells densities change trend was the same as the total densities, and the differences among them were significant, respectively (P < 0.05). The IgG+ cells density in duodenum was the highest, followed by ileum and jejunum and there was significantly difference among them (P < 0.05). The comparison results between Control and Infected groups showed that from the duodenum, jejunum to ileum, IgA+, IgG+, and IgM+ cells were all reduced significantly, respectively. The results suggest that the three types of positive cells were resided heterogeneously in the small intestinal mucosa, that is, significant region-specificity; Moniezia benedeni infection could not change their diffuse distribution characteristics, but strikingly, reduce their resident densities, and the forming mucosal immune barrier were significantly inhibited. It provided powerful evidence for studying on the molecular mechanism of Moniezia benedeni evasion from immune surveillance by strongly inhibiting the host's mucosal immune barrier.

The Role of Vasoactive Intestinal Peptide and Mast Cells in the Regulatory Effect of Lactobacillus casei ATCC 393 on Intestinal Mucosal Immune Barrier.

Vasoactive intestinal peptide (VIP) plays an important role in the neuro-endocrine-immune system. Mast cells (MCs) are important immune effector cells. This study was conducted to investigate the protective effect of L. casei ATCC 393 on Enterotoxigenic Escherichia coli (ETEC) K88-induced intestinal mucosal immune barrier injury and its association with VIP/MC signaling by in vitro experiments in cultures of porcine mucosal mast cells (PMMCs) and in vivo experiments using VIP receptor antagonist (aVIP) drug. The results showed that compared with the ETEC K88 and lipopolysaccharides (LPS)-induced model groups, VIP pretreatment significantly inhibited the activation of MCs and the release of β-hexosaminidase (β-hex), histamine and tryptase. Pretreatment with aVIP abolished the protective effect of L. casei ATCC 393 on ETEC K88-induced intestinal mucosal immune barrier dysfunction in C57BL/6 mice. Also, with the blocking of VIP signal transduction, the ETEC K88 infection increased serum inflammatory cytokines, and the numbers of degranulated MCs in ileum, which were decreased by administration of L. casei ATCC 393. In addition, VIP mediated the regulatory effect of L. casei ATCC 393 on intestinal microbiota in mice. These findings suggested that VIP may mediate the protective effect of L.casei ATCC 393 on intestinal mucosal immune barrier dysfunction via MCs.

Prospects for clinical applications of butyrate-producing bacteria.

As the major source of energy for colonic mucosal cells and as an important regulator of gene expression, inflammation, differentiation, and apoptosis in host cells, microbiota-derived butyrate can enhance the intestinal mucosal immune barrier, modulate systemic immune response, and prevent infections. Maintaining a certain level of butyrate production in the gut can help balance intestinal microbiota, regulate host immune response, and promote the development and maintenance of the intestinal mucosal barrier. Butyrate-producing bacteria act as probiotics and play important roles in a variety of normal biological functions. Bacteriotherapeutic supplementation by using fecal microbiota transplantation to restore butyrate-producing commensal bacteria in the gut has been very successful in the treatment of recurrent and refractory Clostridium difficile (C. difficile) infection or C. difficile-negative nosocomial diarrhea. Administration of probiotics that include butyrate-producing bacteria may have a role in the treatment of inflammatory bowel diseases and in the prevention of necrotizing enterocolitis and late-onset sepsis in premature infants. Furthermore, modulating gut microbiota with dietary approaches may improve intestinal dysbiosis commonly seen in patients with obesity-associated metabolic disorders. Supplementation with a butyrate-producing bacterial stain might be used to increase energy expenditure, improve insulin sensitivity, and to help control obesity and metabolic syndrome.

Potential Roles of Exosomal lncRNAs in the Intestinal Mucosal Immune Barrier.

The intestinal mucosal immune barrier protects the host from the invasion of foreign pathogenic microorganisms. Immune cells and cytokines in the intestinal mucosa maintain local and systemic homeostasis by participating in natural and adaptive immunity. Deficiency of the intestinal mucosal immune barrier is associated with a variety of intestinal illnesses. Exosomes are phospholipid bilayer nanovesicles that allow cell-cell communication by secreting physiologically active substances including proteins, lipids, transcription factors, mRNAs, micro-RNAs (miRNAs), and long noncoding RNAs (lncRNAs). Exosomal lncRNAs are involved in immune cell differentiation and the modulation of the immune response. This review briefly introduces the potential role of exosomal lncRNAs in the intestinal mucosal immune barrier and discusses their relevance to intestinal illnesses.

Changes in bacterial community and expression of genes involved in intestinal innate immunity in the jejunum of newborn lambs during the first 24 hours of life

The newborn gut undergoes rapid colonization by commensal microorganisms and possible exposure to pathogens. The contribution of colostrum intake to host protection is well known; however, limited research exists on the intestinal innate immunity corresponding to colostrum intake during the passive immune transfer period in newborn ruminants. The aim of this study was to investigate the changes in bacterial community and expression of genes encoding toll-like receptors (TLR), mucins (MUC), antimicrobial peptides, and tight junctions in the jejunum of lambs that were fed colostrum during the first 24 h of life. Twenty-seven newborn lambs were used in this study, of which 18 lambs were bottle-fed pooled bovine colostrum within the first 2 h after birth to obtain an intake of approximately 8% of body weight. Lambs were slaughtered at 12 (n = 9) and 24 h (n = 9) after birth. The remaining 9 lambs without any feeding were slaughtered at 30 min after birth (0 h). Tissue and ligated segment samples from the jejunum were collected immediately after the lambs were slaughtered. The bacterial profile in the ligated jejunum segment was assessed using amplicon sequencing. The gene expression in the jejunum tissue was determined using quantitative real-time PCR. The relative abundances of Escherichia-Shigella, Lactobacillus, Lactococcus, and Streptococcus increased, whereas those of Sphingomonas, Phyllobacterium, Bradyrhizobium, and Rudaea decreased during the first 24 h of life. Expression of TLR2 and β-defensin 109-like was upregulated at 12 h after birth, but a recovery was detected at 24 h; TLR3, TLR5, LYZ, MUC1, MUC13, MUC20, and CLDN7 showed a higher expression level in samples taken at 24 h than in those taken at 0 h. In addition, expression level of CLDN1, CLDN4, and the junctional adhesion molecule-1 tended to be higher at 24 h than at 0 h after birth. Correlation analysis indicated that TLR2 expression was negatively correlated with the relative abundance of Lactobacillus and Bradyrhizobium, whereas TLR5 expression was positively correlated with the relative abundance of Escherichia-Shigella and Pelagibacterium. These results suggest that TLR, MUC, antimicrobial peptides, and CLDN act together and play an important role in intestinal defense during the passive immune transfer period. They are potentially associated with microbial colonization. The findings from this study provide novel information to elucidate the role of colostrum components in regulating the development of the intestinal mucosal immune barrier in newborn lambs during the passive immune transfer period.

Sacral nerve stimulating on intestinal mucosal immune barrier function of rats with acute complete spinal cord injury

Objective: To study the effects of sacral nerve root stimulation on intestinal mucosal immune barrier function in rat with acute complete spinal cord injury(SCI). Methods: Fifty-six Wistar rats were divided into Sham group(SG n=8), control group(CG 24 、 48、 72 h,n=8), and experimental group(EG 24、 48、 72 h,n=8). In CG and EG, according to Fehlings'method,we transected the spinal cord by the aneurysm clip and implanted electrodes into the third sacral foramina on the right side.We stimulated in intensity 4 V,the frequency of 15 Hz,and the pulse of 210 μs.The stimulation period was 2 hours,with 10 minutes stimulation and 10 minutes rest intermittently,twice a day at 8:00-10:00 am and 6:00-8:00 pm. The intestinal morphology was observed under light microscope and electron microscope. The protein expression levels of A20,NOD2,and CD68 by Western blot . Results: ① SCI caused impaired intestinal epithelial barrier function. The intestinal mucosa appeared different degree of damage in CG group; cell-cell connections between intestinal epithelial cells were destroyed; The escherichia coli and other antigen translocated through the injured epithelial cell , M cells, and the leakage to the lamina propria of intestinal villi, which were improved in EG after stimulation.② The expression of A20 in EG was increased ,which had statistical differences between CG or SG(P＜0.01); the expression ofA20 in CG was decreased, which had statistical differences between SG(P＜0.01).The expression of NOD2 in CG was increased, which had statistical differences between SG(24 h,72 h P＜0.05; 48 h P＜0.01);The expression of NOD2 in EG (48 h ,72 h)was decreased, which had statistical differences between CG(48 h P＜0.01,72 h P＜0.05). The expression of NOD2 in EG had no statistical differences between SG. The expression of CD68 in CG was increased,which had statistical differences between SG or EG(P＜0.01).The expression of CD68 in EG was increased in 24 h and 48 h groups ,which had statistical differences between SG(P＜0.01),but had no statistical differences in 72 h group. Conclusion: Sacral nerve root 3 electrostimulation can rehabilitate the peristalsis of intestine,decrease bacterial amount,reduce inflammatory response, enhance endogenous protection, protect the intestinal mucosal immune barrier function.

Effects of Astragalus polysaccharides on intestinal morphology and intestinal immune cells of Muscovy ducklings infected with Muscovy duck reovirus

Muscovy duck reovirus (MDRV) infection induces serious immunosuppression and intestinal injury in Muscovy ducklings with a high morbidity and mortality, and Astragalus polysaccharide (APS) pretreatment could efficiently protect ducklings from MDRV infection, although the underlying immunoregulatory mechanisms remain unclear. Thus, the objective of this study was to investigate effects of APS on the intestinal mucosal immunity in MDRV-infected Muscovy ducklings. A total of 190 1-day-old healthy Muscovy ducklings were randomly assigned to 3 groups (n = 50): normal control group, APS pretreatment for MDRV-infected group, and cohabitation infection group, then pretreated with 0.6 g/L APS or only drinking water followed by MDRV cohabitation infection with the remaining 40 artificially infected ducklings, respectively. At the 2, 3, 4, 6, 9 and 15 d after cohabitation infection, the intestinal samples were prepared to measure intestinal parameters including villus length, villus length/crypt depth (V/C) ratio, and wall thickness, together with counts of intraepithelial lymphocyte (IEL) and goblet cell (GC) by hematoxylin–eosin staining. Meanwhile, ileal secretory IgA (sIgA) and duodenal cytokine levels of IL-4, IL-6, IL-15, tumor necrosis factor-alpha, and interferon gamma were detected by the ELISA and radioimmunoassay, respectively. The results showed that APS significantly improved intestinal injuries of villi length, V/C ratio, and wall thickness of the small intestine infected with MDRV, effectively inhibited the reduction of IEL and GC caused by MDRV infection, subsequently increased sIgA and all the cytokine secretions at most time points, suggesting that APS pretreatment can effectively stimulate mucosal immune function by improving intestinal morphology and repair MDRV caused injures of small intestinal mucosal immune barrier in infected ducklings. Our findings lay the foundation for further application of APS in prevention and treatment of MDRV infection.

Progress in Mycotoxins Affecting Intestinal Mucosal Barrier Function.

Mycotoxins, which are widely found in feed ingredients and human food, can exert harmful effects on animals and pose a serious threat to human health. As the first barrier against external pollutants, the intestinal mucosa is protected by a mechanical barrier, chemical barrier, immune barrier, and biological barrier. Firstly, mycotoxins can disrupt the mechanical barrier function of the intestinal mucosa, by destroying the morphology and tissue integrity of the intestinal epithelium. Secondly, mycotoxins can cause changes in the composition of mucin monosaccharides and the expression of intestinal mucin, which in turn affects mucin function. Thirdly, mycotoxins can cause damage to the intestinal mucosal immune barrier function. Finally, the microbiotas of animals closely interact with ingested mycotoxins. Based on existing research, this article reviews the effects of mycotoxins on the intestinal mucosal barrier and its mechanisms.

Enriched environment on the intestinal mucosal barrier and brain–gut axis in rats with colorectal cancer

An enriched environment (EE) is an animal housing technique where animals are given increased amounts of space, physical activity, and social interaction. Presently, researchers studying EEs focus mainly on their effects within the context of neurological diseases. However, little is known about how EEs affect the intestinal mucosal barrier. This study assessed the effects of an EE on the intestinal mucosal barrier in rats with colorectal cancer.

Free Total Rhubarb Anthraquinones Protect Intestinal Injury via Regulation of the Intestinal Immune Response in a Rat Model of Severe Acute Pancreatitis.

Intestinal mucosal immune barrier dysfunction plays a key role in the pathogenesis of severe acute pancreatitis (SAP). Rhubarb is a commonly used traditional Chinese medicine as a laxative in China. It markedly protects pancreatic acinar cells from trypsin-induced injury in rats. Free total rhubarb anthraquinones (FTRAs) isolated and extracted from rhubarb display the beneficial effects of antibacteria, anti-inflammation, antivirus, and anticancer. The principal aim of the present study was to investigate the effects of FTRAs on the protection of intestinal injury and modification of the intestinal barrier function through regulation of intestinal immune function in rats with SAP. We established a rat model of SAP by injecting 3.5% sodium taurocholate (STC, 350 mg/kg) into the biliopancreatic duct via retrograde injection and treated the rats with FTRAs (36 or 72 mg/kg) or normal saline (control) immediately and 12 h after STC injection. Then, we evaluated the protective effect of FTRAs on intestinal injury by pathological analysis and determined the levels of endotoxin (ET), interleukin 1β (IL-1β), tumor necrosis factor α (TNF-α), nitric oxide (NO), myeloperoxidase (MPO), capillary permeability, nucleotide-binding oligomerization domain-like receptors 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD domain (ASC), casepase-1, secretary immunoglobulin A (SIgA), regulatory T cells (Tregs), and the ratio of Th1/Th2 in the blood and/or small intestinal tissues or mesenteric lymph node (MLN) cells. Moreover, the chemical profile of FTRAs was analyzed by HPLC-UV chromatogram. The results showed that FTRAs significantly protected intestinal damage and decreased the levels of ET, IL-1β, TNF-α, and NO in the blood and TNF-α, IL-1β, and protein extravasation in the intestinal tissues in SAP rats. Furthermore, FTRAs significantly decreased the expressions of NLRP3, ASC, and caspase-1, the number of Tregs and the ratio of Th1/Th2, while significantly increased the expression of SIgA in the intestinal tissues and/or MLN cells in SAP rats. Our results indicate that FTRAs could protect intestinal injury and improve intestinal mucosal barrier function through regulating immune function of SAP rats. Therefore, FTRAs may have the potential to be developed as the novel agent for the treatment of SAP clinically.

Hericium erinaceus polysaccharide facilitates restoration of injured intestinal mucosal immunity in Muscovy duck reovirus-infected Muscovy ducklings

To elucidate the effect of Hericium erinaceus polysaccharide (HEP) on the intestinal mucosal immunity in normal and Muscovy duck reovirus (MDRV)-infected Muscovy ducklings, 1-day-old healthy Muscovy ducklings were pretreated with 0.2g/L HEP and/or following by MDRV infection in this study, duodenal samples were respectively collected at 1, 3, 6, 10, 15 and 21day post-infection, tissue sections were prepared for observation of morphological structure and determination of intestinal parameters (villus height/crypt depth ratio, villus surface area) as well as counts of intraepithelial lymphocytes (IELs), goblet cells, mast cells. Additionally, dynamics of secretory immunoglobin A (sIgA), interferon-γ (IFN-γ) and interleukin-4 (IL-4) productions in intestinal mucosa were measured with radioimmunoassay. Results showed that HEP significantly improved intestinal morphological structure and related indexes, and significantly inhibited the reduction of intestinal mucosal IELs, goblet cells and mast cells caused by MDRV infection. Furthermore, HEP significantly increased the secretion of sIgA, IFN-γ and IL-4 to enhance intestinal mucosal immune functions. Our findings indicate that HEP treatment can effectively repair MDRV-caused injures of small intestinal mucosal immune barrier, and improve mucosal immune function in sick Muscovy ducklings, which will provide valuable help for further application of HEP in prevention and treatment of MDRV infection.

Relationship between nutritional status and intestinal mucosal immune barrier in patients with stage IV chronic kidney disease: Curative effect of Chinese herbal colon dialysis

Relationship between nutritional status and intestinal mucosal immune barrier in patients with stage IV chronic kidney disease: Curative effect of Chinese herbal colon dialysis

Allergens and intestinal damage induced by soybean antigen proteins in weaned piglets

This study was conducted to investigate the effects of soybean antigen proteins on serum cytokine levels and claudin-1 distribution in the intestine of weaned piglets. Seventy piglets (24 d of age) were randomly divided into seven groups. Piglets in group A were fed a basal diet, in groups B, C and D were fed the basal diet supplemented with β-conglycinin; and in groups E, F, G were fed the basal diet supplemented with glycinin. Blood samples were collected and analysed for IFN-γ, IL-2, IL-4 and IL-6 levels on day 24, 26, 28 and 30. At the end of the trial, five piglets per group were sacrificed and the small intestine was collected to evaluate intestinal claudin-1 distribution and OD of the relative staining positivity. β-Conglycinin and glycinin decreased the growth performance in piglets by decreasing ADFI, ADG and increasing F/G. Serum levels of IL-2, IL-4 and IL-6 in β-conglycinin and glycinin groups ranged from 126.067 to 144.067 ng • L−1, 31.798 to 44.360 ng • L−1 and 36.360 to 40.482 ng • L−1 on day 24, 26 and 30. However, serum IFN-γ levels were negatively correlated with soybean antigen proteins supplementation levels ranged from 6.956 to 15.361 ng • L−1. The treatment groups had lower OD values of claudin-1 than those of the control group. The β-conglycinin groups had lower distribution and OD values than the glycinin groups at similar antigen protein supplementation levels. These results suggest that β-conglycinin and glycinin damage the intestinal mucosal immune barrier in weaned piglets.

Herbal prescription Chang'an II repairs intestinal mucosal barrier in rats with post-inflammation irritable bowel syndrome.

The herbal prescription Chang'an II is derived from a classical TCM formula Tong-Xie-Yao-Fang for the treatment of liver-qi stagnation and spleen deficiency syndrome of irritable bowel syndrome (IBS). In this study we investigated the effects of Chang'an II on the intestinal mucosal immune barrier in a rat post-inflammation IBS (PI-IBS) model. A rat model of PI-IBS was established using a multi-stimulation paradigm including early postnatal sibling deprivation, bondage and intrarectal administration of TNBS. Four weeks after TNBS administration, the rats were treated with Chang'an II (2.85, 5.71 and 11.42 g · kg(-1) · d(-1), ig) for 14 d. Intestinal sensitivity was assessed based on the abdominal withdrawal reflex (AWR) scores and fecal water content. Open field test and two-bottle sucrose intake test were used to evaluate the behavioral changes. CD4(+) and CD8(+) cells were counted and IL-1β and IL-4 levels were measured in intestinal mucosa. Transmission electron microscopy was used to evaluate ultrastructural changes of the intestinal mucosal barrier. PI-IBS model rats showed significantly increased AWR reactivity and fecal water content, and decreased locomotor activity and sucrose intake. Chang'an II treatment not only reduced AWR reactivity and fecal water content, but also suppressed the anxiety and depressive behaviors. Ultrastructural study revealed that the gut mucosal barrier function was severely damaged in PI-IBS model rats, whereas Chang'an II treatment relieved intestinal mucosal inflammation and repaired the gut mucosal barrier. Furthermore, PI-IBS model rats showed a significantly reduced CD4(+)/CD8(+) cell ratio in lamina propria and submucosa, and increased IL-1β and reduced IL-4 expression in intestinal mucosa, whereas Chang'an II treatment reversed PI-IBS-induced changes in CD4(+)/CD8(+) cell ratio and expression of IL-1β and IL-4. Chang'an II treatment protects the intestinal mucosa against PI-IBS through anti-inflammatory, immunomodulatory and anti-anxiety effects.