Food antigens exacerbate intestinal damage and inflammation following the disruption of the mucosal barrier

2021 ◽  
Vol 96 ◽  
pp. 107670
Author(s):  
Yanmei Ma ◽  
Zhihua Yin ◽  
Li Li ◽  
Bingni Chen ◽  
Hanying Dai ◽  
...  
Keyword(s):  
Mucosal Barrier ◽  
Intestinal Damage ◽  
Food Antigens

scholarly journals Betulinic Acid Ameliorates the T-2 Toxin-Triggered Intestinal Impairment in Mice by Inhibiting Inflammation and Mucosal Barrier Dysfunction through the NF-κB Signaling Pathway

Toxins ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 794
Author(s):  
Chenxi Luo ◽  
Chenglong Huang ◽  
Lijuan Zhu ◽  
Li Kong ◽  
Zhihang Yuan ◽  
...  
Keyword(s):  
Protective Effect ◽  
Antioxidant Capacity ◽  
Signaling Pathway ◽  
Inflammatory Cytokines ◽  
Betulinic Acid ◽  
Molecular Mechanisms ◽  
Mucosal Barrier ◽  
Intestinal Damage ◽  
Trichothecene Mycotoxin ◽  
Anti Inflammatory

T-2 toxin, a trichothecene mycotoxin produced by Fusarium, is widely distributed in crops and animal feed and frequently induces intestinal damage. Betulinic acid (BA), a plant-derived pentacyclic lupane-type triterpene, possesses potential immunomodulatory, antioxidant and anti-inflammatory biological properties. The current study aimed to explore the protective effect and molecular mechanisms of BA on intestinal mucosal impairment provoked by acute exposure to T-2 toxin. Mice were intragastrically administered BA (0.25, 0.5, or 1 mg/kg) daily for 2 weeks and then injected intraperitoneally with T-2 toxin (4 mg/kg) once to induce an intestinal impairment. BA pretreatment inhibited the loss of antioxidant capacity in the intestine of T-2 toxin-treated mice by elevating the levels of CAT, GSH-PX and GSH and reducing the accumulation of MDA. In addition, BA pretreatment alleviated the T-2 toxin-triggered intestinal immune barrier dysregulation by increasing the SIgA level in the intestine at dosages of 0.5 and 1 mg/kg, increasing IgG and IgM levels in serum at dosages of 0.5 and 1 mg/kg and restoring the intestinal C3 and C4 levels at a dosage of 1 mg/kg. BA administration at a dosage of 1 mg/kg also improved the intestinal chemical barrier by decreasing the serum level of DAO. Moreover, BA pretreatment improved the intestinal physical barrier via boosting the expression of ZO-1 and Occludin mRNAs and restoring the morphology of intestinal villi that was altered by T-2 toxin. Furthermore, treatment with 1 mg/kg BA downregulated the expression of p-NF-κB and p-IκB-α proteins in the intestine, while all doses of BA suppressed the pro-inflammatory cytokines expression of IL-1β, IL-6 and TNF-α mRNAs and increased the anti-inflammatory cytokine expression of IL-10 mRNA in the intestine of T-2 toxin-exposed mice. BA was proposed to exert a protective effect on intestinal mucosal disruption in T-2 toxin-stimulated mice by enhancing the intestinal antioxidant capacity, inhibiting the secretion of inflammatory cytokines and repairing intestinal mucosal barrier functions, which may be associated with BA-mediated inhibition of the NF-κB signaling pathway activation.

scholarly journals Probiotic Mixture Protects Dextran Sulfate Sodium-Induced Colitis by Altering Tight Junction Protein Expressions and Increasing Tregs

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Yingdi Zhang ◽  
Xiaojing Zhao ◽  
Yunjuan Zhu ◽  
Jingjing Ma ◽  
Haiqin Ma ◽  
...  
Keyword(s):  
Tight Junction ◽  
Peripheral Blood ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Intestinal Inflammation ◽  
Experimental Colitis ◽  
Mucosal Barrier ◽  
Intestinal Damage ◽  
Protective Effects ◽  
Junction Protein

Bifico is a probiotic mixture containing Bifidobacterium, Lactobacillus acidophilus, and Enterococcus. Studies support that Bifico has a protective effect in experimental colitis (IL-10-deficient and TNBS) models and in patients with inflammatory bowel disease (IBD). However, the mechanism underlying the protective effects of this mixture of probiotic bacteria remains incompletely clear. Here, we investigated the effect of Bifico on intestinal inflammation. In an in vivo experiment, dextran sulfate sodium was used to induce colitis. Bifico treatment significantly attenuated the severity of colitis in this model. Bifico increased the expression of tight junction proteins (TJs). In addition, Bifico increased the number of Tregs, but reduced the number of total CD4+ T cells in the peripheral blood. Furthermore, the expression of colonic CD4 protein was decreased while the level of forkhead box P3 (Foxp3) was upregulated. These results suggested that Bifico exerts beneficial effects on experimental colitis by increasing the expressions of TJs, upregulating the number of Tregs, and reducing the total CD4+ T cell number in both colon and peripheral blood. The intestinal damage in the pretreated + treated-Bifico-colitis group was more severe than that in only the pretreated-Bifico-colitis group. This suggested that Bifico might aggravate intestinal damage when the mucosal barrier is impaired.

scholarly journals Probiotics Mixture Reinforces Barrier Function to Ameliorate Necrotizing Enterocolitis by Regulating PXR-JNK Pathway

2020 ◽  
Author(s):  
Xiuhao Zhao ◽  
Jin Zhou ◽  
Wenhua Liang ◽  
Qingfeng Sheng ◽  
Li Lu ◽  
...  
Keyword(s):  
Tight Junction ◽  
Necrotizing Enterocolitis ◽  
Animal Experiments ◽  
Intestinal Barrier ◽  
Pregnane X Receptor ◽  
Mucosal Barrier ◽  
Intestinal Damage ◽  
Jnk Pathway ◽  
Intestinal Lesions ◽  
Neonatal Necrotizing Enterocolitis

Abstract Background: Intestinal dysbiosis is believed to be one of the factors inducing neonatal necrotizing enterocolitis (NEC). Probiotics have been employed to treat NEC in a number of animal experiments and clinical trials, and some significant benefits of utilizing probiotics for the prevention or alleviation of NEC have been confirmed. However, the mechanism underlying the efficacy of probiotics in treating NEC has not been elucidated. Results: Impairment of the intestinal barrier, which was characterized by the decreased expression of tight junction components, was observed in the pathogenesis of NEC. The probiotic mixture alleviated this intestinal damage by enhancing the function of the barrier. Meanwhile, the probiotics remodeled the composition of the intestinal microbiota in NEC mice. Furthermore, increased expression of the pregnane X receptor ( PXR ) was observed after treatment with the probiotic mixture, and PXR overexpression in Caco-2 cells protected the barrier from lipopolysaccharide (LPS) damage. Further research showed that PXR could inhibit the phosphorylation of c-Jun N-terminal kinase (JNK) and could increase the expression of tight junction components. Conclusions: Our study confirmed that probiotics could ameliorate intestinal lesions by enhancing the function of the mucosal barrier. Specifically, probiotics may target PXR, which may subsequently enhance the expression of tight junction components by inhibiting the phosphorylation of JNK and enhancing the function of the barrier.

scholarly journals Low Molecular Seleno-Aminopolysaccharides Protect the Intestinal Mucosal Barrier of Rats under Weaning Stress

2019 ◽  
Vol 20 (22) ◽  
pp. 5727 ◽  
Author(s):  
Zheng-Shun Wen ◽  
Ming Du ◽  
Zhen Tang ◽  
Tian-Yi Zhou ◽  
Zhong-Shan Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Protective Effect ◽  
Intestinal Mucosa ◽  
Expression Level ◽  
Mucosal Barrier ◽  
Intestinal Damage ◽  
Intestinal Tissue ◽  
Intestinal Mucosal Barrier ◽  
Weaning Stress ◽  
Nrf2 Signaling Pathway

Low molecular seleno-aminopolysaccharide (LSA) was synthesized with sodium selenite and low molecular aminopolysaccharide (LA), which is an organic selenium compound. This study is aimed to investigate the protective effect of LSA on the intestinal mucosal barrier in weaning stress rats by detecting the intestinal tissue morphology and function, mucosal thickness and permeability, the structure of MUC2, antioxidant index, the expression level of intracellular transcription factor NF-E2-related factor 2 (Nrf2), and its related factors. The results showed that LSA significantly increased the height of intestinal villi (p < 0.05) and increased the thickness of intestinal mucosa and the number of goblet cells, which indicated that LSA has a protective effect on the intestinal mucosal barrier that is damaged by weaning. Moreover, LSA significantly reduced the level of DAO, D-LA, and LPS compared with the weaning group (p < 0.05), which indicated that LSA reduced the intestinal damage and permeability of weaning rats. In addition, LSA could increase the number and length of glycans chains and the abundance of acid glycans structures in the MUC2 structure, which indicated that LSA alleviated the changes of intestinal mucus protein structure. LSA significantly increased the levels of GSH-Px, SOD, LDH, and CAT, while it decreased the level of MDA in serum and intestinal tissue, which suggested that LSA significantly enhanced the antioxidant capacity and reduced oxidative stress of weaning rats. RT-PCR results showed that LSA significantly increased the expression level of antioxidant genes (GSH-Px, SOD, Nrf2, HO-1), glycosyltransferase genes (GalNT1, GalNT3, GalNT7) and mucin gene (MUC2) in intestinal mucosa (p < 0.05). The results of western blot showed that the LSA activated the Nrf2 signaling pathway by down-regulating the expression of Keap1and up-regulating the expression of Nrf2, and protected the intestinal mucosa from oxidative stress. Overall, LSA could play a protective role in intestinal mucosal barrier of weaning rats by activating the Nrf2 pathway and alleviating the alnormal change of mucin MUC2.

scholarly journals Probiotics mixture reinforces barrier function to ameliorate necrotizing enterocolitis by regulating PXR-JNK pathway

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xiuhao Zhao ◽  
Jin Zhou ◽  
Wenhua Liang ◽  
Qingfeng Sheng ◽  
Li Lu ◽  
...  
Keyword(s):  
Tight Junction ◽  
Necrotizing Enterocolitis ◽  
Animal Experiments ◽  
Intestinal Barrier ◽  
Pregnane X Receptor ◽  
Mucosal Barrier ◽  
Intestinal Damage ◽  
Jnk Pathway ◽  
Intestinal Lesions ◽  
Neonatal Necrotizing Enterocolitis

Abstract Background Intestinal dysbiosis is believed to be one of the factors inducing neonatal necrotizing enterocolitis (NEC). Probiotics have been employed to treat NEC in a number of animal experiments and clinical trials, and some significant benefits of utilizing probiotics for the prevention or alleviation of NEC have been confirmed. However, the mechanism underlying the efficacy of probiotics in treating NEC has not been elucidated. Results Impairment of the intestinal barrier, which was characterized by the decreased expression of tight junction components, was observed in the pathogenesis of NEC. The probiotic mixture alleviated this intestinal damage by enhancing the function of the barrier. Meanwhile, the probiotics remodeled the composition of the intestinal microbiota in NEC mice. Furthermore, increased expression of the pregnane X receptor (PXR) was observed after treatment with the probiotic mixture, and PXR overexpression in Caco-2 cells protected the barrier from lipopolysaccharide (LPS) damage. Further research showed that PXR could inhibit the phosphorylation of c-Jun N-terminal kinase (JNK) and could increase the expression of tight junction components. Conclusions Our study confirmed that probiotics could ameliorate intestinal lesions by enhancing the function of the mucosal barrier. Specifically, probiotics may target PXR, which may subsequently enhance the expression of tight junction components by inhibiting the phosphorylation of JNK and enhance the function of the barrier.

scholarly journals Beneficial Effect of Mildly Pasteurized Whey Protein on Intestinal Integrity and Innate Defense in Preterm and Near-Term Piglets

Nutrients ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 1125 ◽  
Author(s):  
Marit Navis ◽  
Vanesa Muncan ◽  
Per Torp Sangild ◽  
Line Møller Willumsen ◽  
Pim J. Koelink ◽  
...  
Keyword(s):  
Enteral Nutrition ◽  
Whey Protein ◽  
Whey Protein Concentrate ◽  
Mucosal Barrier ◽  
Intestinal Damage ◽  
Innate Defense ◽  
Near Term ◽  
C 30 ◽  
The Impact ◽  
Gut Maturation

Background. The human digestive tract is structurally mature at birth, yet maturation of gut functions such as digestion and mucosal barrier continues for the next 1–2 years. Human milk and infant milk formulas (IMF) seem to impact maturation of these gut functions differently, which is at least partially related to high temperature processing of IMF causing loss of bioactive proteins and formation of advanced glycation end products (AGEs). Both loss of protein bioactivity and formation of AGEs depend on heating temperature and time. The aim of this study was to investigate the impact of mildly pasteurized whey protein concentrate (MP-WPC) compared to extensively heated WPC (EH-WPC) on gut maturation in a piglet model hypersensitive to enteral nutrition. Methods. WPC was obtained by cold filtration and mildly pasteurized (73 °C, 30 s) or extensively heat treated (73 °C, 30 s + 80 °C, 6 min). Preterm (~90% gestation) and near-term piglets (~96% gestation) received enteral nutrition based on MP-WPC or EH-WPC for five days. Macroscopic and histologic lesions in the gastro-intestinal tract were evaluated and intestinal responses were further assessed by RT-qPCR, immunohistochemistry and enzyme activity analysis. Results. A diet based on MP-WPC limited epithelial intestinal damage and improved colonic integrity compared to EH-WPC. MP-WPC dampened colonic IL1-β, IL-8 and TNF-α expression and lowered T-cell influx in both preterm and near-term piglets. Anti-microbial defense as measured by neutrophil influx in the colon was only observed in near-term piglets, correlated with histological damage and was reduced by MP-WPC. Moreover, MP-WPC stimulated iALP activity in the colonic epithelium and increased differentiation into enteroendocrine cells compared to EH-WPC. Conclusions. Compared to extensively heated WPC, a formula based on mildly pasteurized WPC limits gut inflammation and stimulates gut maturation in preterm and near-term piglets and might therefore also be beneficial for preterm and (near) term infants.

scholarly journals Probiotics Mixture Reinforces Barrier Function to Ameliorate Necrotizing Enterocolitis by Regulating PXR-JNK Pathway

2020 ◽  
Author(s):  
Xiuhao Zhao ◽  
Jin Zhou ◽  
Wenhua Liang ◽  
Qingfeng Sheng ◽  
Li Lu ◽  
...  
Keyword(s):  
Tight Junction ◽  
Necrotizing Enterocolitis ◽  
Animal Experiments ◽  
Intestinal Barrier ◽  
Pregnane X Receptor ◽  
Mucosal Barrier ◽  
Intestinal Damage ◽  
Jnk Pathway ◽  
Intestinal Lesions ◽  
Neonatal Necrotizing Enterocolitis

Abstract Background: Intestinal dysbiosis is believed to be one of the factors inducing neonatal necrotizing enterocolitis (NEC). Probiotics have been employed to treat NEC in a number of animal experiments and clinical trials, and some significant benefits of utilizing probiotics for the prevention or alleviation of NEC have been confirmed. However, the mechanism underlying the efficacy of probiotics in treating NEC has not been elucidated.Results: Impairment of the intestinal barrier, which was characterized by the decreased expression of tight junction components, was observed in the pathogenesis of NEC. The probiotic mixture alleviated this intestinal damage by enhancing the function of the barrier. Meanwhile, the probiotics remodeled the composition of the intestinal microbiota in NEC mice. Furthermore, increased expression of the pregnane X receptor (PXR) was observed after treatment with the probiotic mixture, and PXR overexpression in Caco-2 cells protected the barrier from lipopolysaccharide (LPS) damage. Further research showed that PXR could inhibit the phosphorylation of c-Jun N-terminal kinase (JNK) and could increase the expression of tight junction components.Conclusions: Our study confirmed that probiotics could ameliorate intestinal lesions by enhancing the function of the mucosal barrier. Specifically, probiotics may target PXR, which may subsequently enhance the expression of tight junction components by inhibiting the phosphorylation of JNK and enhancing the function of the barrier.

scholarly journals Emodin Improves Intestinal Health and Immunity through Modulation of Gut Microbiota in Mice Infected by Pathogenic Escherichia coli O1

Animals ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 3314
Author(s):  
Ruijuan Gao ◽  
Chunjie Wang ◽  
Aricha Han ◽  
Yanping Tian ◽  
Shunan Ren ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Intestinal Microbiota ◽  
Goblet Cells ◽  
Mucosal Barrier ◽  
Intestinal Damage ◽  
Mrna Levels ◽  
Rt Pcr ◽  
Intestinal Mucosal Barrier ◽  
E Coli ◽  
Mucosal Barrier Function

The effect of emodin on the intestinal mucosal barrier of a mouse E. coli O1-induced diarrhea model was observed. Following successful establishment of a diarrhea model, the mice were treated with drugs for seven days. Intestinal lesions and the shape and the number of goblet cells were assessed via hematoxylin-eosin and periodic-acid-Schiff staining, while changes in inflammatory factors, ultrastructure of the small intestine, expression of MUC-2, and changes in the intestinal microbiota were analyzed via RT-PCR, electron microscopy, immunofluorescence, and 16S rRNA sequencing. Examination showed that emodin ameliorated pathological damage to the intestines of diarrheic mice. RT-PCR indicated that emodin reduced TNF-α, IL-β, IL-6, MPO, and COX-2 mRNA levels in duodenal tissues and increased the levels of sIgA and MUC-2 and the number of goblet cells. Microbiome analysis revealed that Escherichia coli O1 reduced bacterial richness and altered the distribution pattern of bacterial communities at the phylum and order levels in cecum contents. Notably, pathogenic Clostridiales and Enterobacteriales were significantly increased in diarrheic mice. However, emodin reversed the trend. Thus, emodin protected against intestinal damage induced by E. coli O1 and improved intestinal mucosal barrier function in mice by increasing the abundance of beneficial intestinal microbiota and inhibiting the abundance of harmful bacteria, thereby alleviating diarrhea.

scholarly journals Probiotics Mixture Reinforces Barrier Function to Ameliorate Necrotizing Enterocolitis by Regulating PXR-JNK Pathway

2021 ◽  
Author(s):  
Xiuhao Zhao ◽  
Jin Zhou ◽  
Wenhua Liang ◽  
Qingfeng Sheng ◽  
Li Lu ◽  
...  
Keyword(s):  
Tight Junction ◽  
Necrotizing Enterocolitis ◽  
Animal Experiments ◽  
Intestinal Barrier ◽  
Pregnane X Receptor ◽  
Mucosal Barrier ◽  
Intestinal Damage ◽  
Jnk Pathway ◽  
Intestinal Lesions ◽  
Neonatal Necrotizing Enterocolitis

Abstract Background: Intestinal dysbiosis is believed to be one of the factors inducing neonatal necrotizing enterocolitis (NEC). Probiotics have been employed to treat NEC in a number of animal experiments and clinical trials, and some significant benefits of utilizing probiotics for the prevention or alleviation of NEC have been confirmed. However, the mechanism underlying the efficacy of probiotics in treating NEC has not been elucidated.Results: Impairment of the intestinal barrier, which was characterized by the decreased expression of tight junction components, was observed in the pathogenesis of NEC. The probiotic mixture alleviated this intestinal damage by enhancing the function of the barrier. Meanwhile, the probiotics remodeled the composition of the intestinal microbiota in NEC mice. Furthermore, increased expression of the pregnane X receptor (PXR) was observed after treatment with the probiotic mixture, and PXR overexpression in Caco-2 cells protected the barrier from lipopolysaccharide (LPS) damage. Further research showed that PXR could inhibit the phosphorylation of c-Jun N-terminal kinase (JNK) and could increase the expression of tight junction components.Conclusions: Our study confirmed that probiotics could ameliorate intestinal lesions by enhancing the function of the mucosal barrier. Specifically, probiotics may target PXR, which may subsequently enhance the expression of tight junction components by inhibiting the phosphorylation of JNK and enhancing the function of the barrier.

Research Advances in Protective Effects of Ursolic Acid and Oleanolic Acid Against Gastrointestinal Diseases

2021 ◽  
pp. 1-23
Author(s):  
Yajing Shi ◽  
Yufang Leng ◽  
Disheng Liu ◽  
Xin Liu ◽  
Yixing Ren ◽  
...  
Keyword(s):  
Ursolic Acid ◽  
Oleanolic Acid ◽  
Barrier Function ◽  
Intestinal Tract ◽  
Gastrointestinal Diseases ◽  
Mucosal Barrier ◽  
Intestinal Damage ◽  
Protective Function ◽  
Triterpene Acid ◽  
Systemic Complications

The intestinal tract plays an essential role in protecting tissues from the invasion of external harmful substances due to impaired barrier function. Furthermore, it participates in immunomodulation by intestinal microorganisms, which is important in health. When the intestinal tract is destroyed, it can lose its protective function, resulting in multiple systemic complications. In severe cases, it may lead to systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS). Thus far, there are no curative therapies for intestinal mucosal barrier injury, other than a few drugs that can relieve symptoms. Thus, the development of novel curative agents for gastrointestinal diseases remains a challenge. Ursolic acid (UA) and its isomer, Oleanolic acid (OA), are pentacyclic triterpene acid compounds. Both their aglycone and glycoside forms have anti-oxidative, anti-inflammatory, anti-ulcer, antibacterial, antiviral, antihypertensive, anti-obesity, anticancer, antidiabetic, cardio protective, hepatoprotective, and anti-neurodegenerative properties in living organisms. In recent years, several studies have shown that UA and OA can reduce the risk of intestinal pathological injury, alleviate intestinal dysfunction, and restore intestinal barrier function. The present study evaluated the beneficial effects of UA and OA on intestinal damage and diseases, including inflammatory bowel disease (IBD) and colorectal cancer (CRC).

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