scholarly journals The Protective Effects of Lactoferrin on Aflatoxin M1-Induced Compromised Intestinal Integrity

2021 ◽  
Vol 23 (1) ◽  
pp. 289
Author(s):  
Ya-Nan Gao ◽  
Song-Li Li ◽  
Xue Yang ◽  
Jia-Qi Wang ◽  
Nan Zheng
Keyword(s):  
Adherens Junction ◽  
Intestinal Barrier ◽  
Mapk Signaling ◽  
Regulatory Subunit ◽  
Intestinal Cell ◽  
Aflatoxin M1 ◽  
Protective Effects ◽  
Barrier Dysfunction ◽  
Intestinal Integrity ◽  
Study Results

Aflatoxin M1 (AFM1), the only toxin with maximum residue levels in milk, has adverse effects on the intestinal barrier, resulting in intestinal inflammatory disease. Lactoferrin (LF), one of the important bioactive proteins in milk, performs multiple biological functions, but knowledge of the protective effects of LF on the compromised intestinal barrier induced by AFM1 has not been investigated. In the present study, results using Balb/C mice and differentiated Caco-2 cells showed that LF intervention decreased AFM1-induced increased intestinal permeability, improved the protein expression of claudin-3, occludin and ZO-1, and repaired the injured intestinal barrier. The transcriptome and proteome were used to clarify the underlying mechanisms. It was found that LF reduced the intestinal barrier dysfunction caused by AFM1 and was associated with intestinal cell survival related pathways, such as cell cycle, apoptosis and MAPK signaling pathway and intestinal integrity related pathways including endocytosis, tight junction, adherens junction and gap junction. The cross-omics analysis suggested that insulin receptor (INSR), cytoplasmic FMR1 interacting protein 2 (CYFIP2), dedicator of cytokinesis 1 (DOCK1) and ribonucleotide reductase regulatory subunit M2 (RRM2) were the potential key regulators as LF repaired the compromised intestinal barrier. These findings indicated that LF may be an alternative treatment for the compromised intestinal barrier induced by AFM1.

Protective effects of selenium nanoparticle-enriched Lactococcus lactis NZ9000 against enterotoxigenic Escherichia coli K88-induced intestinal barrier damage in mice

2021 ◽  
Author(s):  
Yue Chen ◽  
Lei Qiao ◽  
Xiaofan Song ◽  
Li Ma ◽  
Xina Dou ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Lactococcus Lactis ◽  
Sodium Selenite ◽  
Low Cost ◽  
Intestinal Barrier ◽  
Feed Additives ◽  
Enterotoxigenic Escherichia Coli ◽  
Protective Effects ◽  
Barrier Dysfunction ◽  
Wide Range

Composite microecological agents have received widespread attention due to their advantageous properties, including safety, multi-effects, and low cost. This study was conducted to evaluate the protective effects of selenium (Se) nanoparticle-enriched Lactococcus lactis NZ9000 ( L. lactis NZ9000-SeNPs) against enterotoxigenic Escherichia coli K88 (ETEC K88)-induced intestinal barrier damage in C57BL/6 mice. Oral administration of L. lactis NZ9000-SeNPs significantly increased the villi height and the number of goblet cells in the ileum, and reduced the levels of serum and ileal interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ), and increased the activities of thioredoxin reductase (TrxR) and glutathione peroxidase (GSH-Px) compared with the ETEC K88-infected group not treated with L. lactis NZ9000-SeNPs. In addition, L. lactis NZ9000-SeNPs significantly attenuated the reduction of the expression levels of occludin and claudin-1, dysbiosis of the gut microbiome, and the activation of toll-like receptor (TLR)/nuclear factor-kappa (NF-κB)-mediated signaling pathway induced by ETEC K88. These findings suggested that L. lactis NZ9000-SeNPs may be a promising and safe Se supplement for food or feed additives. Importance The beneficial effects of microecological agents have been widely proven. Se, which is nutritionally essential trace element for human and animals, is incorporated into selenoproteins that have a wide range of pleiotropic effects, ranging from antioxidant and anti-inflammatory effects. However, the sodium selenite, a common addition form of Se in feed and food, has disadvantages such as strong toxicity and low bioavailability. We investigated the protective effects of L. lactis NZ9000-SeNPs against ETEC K88-induced intestinal barrier injury in C57BL/6 mice. Our results show that L. lactis NZ9000-SeNPs effectively alleviate ETEC-K88-induced intestinal barrier dysfunction. This study highlights the importance of developing a promising and safe Se supplement for the substation of sodium selenite applied in food, feed and biomedicine.

scholarly journals Aflatoxin B1 and Aflatoxin M1 Induce Compromised Intestinal Integrity through Clathrin-Mediated Endocytosis

Toxins ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 184
Author(s):  
Yanan Gao ◽  
Xiaoyu Bao ◽  
Lu Meng ◽  
Huimin Liu ◽  
Jiaqi Wang ◽  
...  
Keyword(s):  
Aflatoxin B1 ◽  
Intestinal Barrier ◽  
Fluorescein Isothiocyanate ◽  
Intestinal Barrier Function ◽  
Aflatoxin M1 ◽  
Dependent Manner ◽  
Simultaneous Exposure ◽  
Intestinal Integrity

With the growing diversity and complexity of diet, humans are at risk of simultaneous exposure to aflatoxin B1 (AFB1) and aflatoxin M1 (AFM1), which are well-known contaminants in dairy and other agricultural products worldwide. The intestine represents the first barrier against external contaminants; however, evidence about the combined effect of AFB1 and AFM1 on intestinal integrity is lacking. In vivo, the serum biochemical parameters related to intestinal barrier function, ratio of villus height/crypt depth, and distribution pattern of claudin-1 and zonula occluden-1 were significantly affected in mice exposed to 0.3 mg/kg b.w. AFB1 and 3.0 mg/kg b.w. AFM1. In vitro results on differentiated Caco-2 cells showed that individual and combined AFB1 (0.5 and 4 μg/mL) and AFM1 (0.5 and 4 μg/mL) decreased cell viability and trans-epithelial electrical resistance values as well as increased paracellular permeability of fluorescein isothiocyanate-dextran in a dose-dependent manner. Furthermore, AFM1 aggravated AFB1-induced compromised intestinal barrier, as demonstrated by the down-regulation of tight junction proteins and their redistribution, particularly internalization. Adding the inhibitor chlorpromazine illustrated that clathrin-mediated endocytosis partially contributed to the compromised intestinal integrity. Synergistic and additive effects were the predominant interactions, suggesting that these toxins are likely to have negative effects on human health.

scholarly journals Oxyresveratrol protective effects against deoxynivalenol-induced intestinal barrier dysfunction and bacterial translocation on porcine intestinal epithelial IPEC-J2 cells

2018 ◽  
Vol 1 ◽  
Author(s):  
Murphy L.Y. Wan ◽  
Ka Ho Ling ◽  
Hani El-Nezami ◽  
Mingfu Wang
Keyword(s):  
Bacterial Translocation ◽  
Barrier Function ◽  
Intestinal Barrier ◽  
Mitogen Activated Protein Kinase ◽  
Intestinal Barrier Function ◽  
Epithelial Barrier ◽  
Intestinal Damage ◽  
Protective Effects ◽  
Barrier Dysfunction ◽  
Significant Difference

Deoxynivalenol (DON) is a major mycotoxin contaminant and is known to impair intestinal barrier function. Previous experiments in our laboratory have proven that polyphenols such as resveratrol (RES) may be effective in enhancing epithelial barrier function. Due to the structural similarity of oxyresveratrol (OXY) with RES, it was hypothesized that OXY could also protect against DON-induced intestinal damage. Accordingly, this study aimed to explore potential protective effects of OXY against DON-induced epithelial barrier dysfunction and bacterial translocation on IPEC-J2 cells, in comparison to resveratrol (RES).The results showed that OXY increased transepithelial electrical resistance (TEER) and reduced FD-4 diffusion, whereas DON reduced TEER and increased FD-4 diffusion in IPEC-J2 cells. On the other hand, OXY reduced FD-4 diffusion in DON-damaged cells but showed no significant difference in terms of TEER. Such protective effects coincided with the significantly reduced E. coli translocation in cells co-exposed to DON and OXY. Further mechanistic studies demonstrated that OXY protected against DON-induced barrier dysfunction by enhancing the expression of claudin-4 via mitogen-activated protein kinase(MAPK)-dependent pathways. Apparently, OXY worked through the same way as RES did, with results dovetailed nicely with anticipation. These results imply that OXY may share similar health benefits with RES by enhancing epithelial barrier functions and protecting against DON-induced intestinal damage.

scholarly journals Protective Effects of Let-7b on the Expression of Occludin by Targeting P38 MAPK in Preventing Intestinal Barrier Dysfunction

2018 ◽  
Vol 45 (1) ◽  
pp. 343-355 ◽  
Author(s):  
Zhihua Liu ◽  
Yinghai Tian ◽  
Yanqiong Jiang ◽  
Shihua Chen ◽  
Ting Liu ◽  
...  
Keyword(s):  
P38 Mapk ◽  
Barrier Function ◽  
Intestinal Barrier ◽  
Conditional Knockout ◽  
Intestinal Barrier Function ◽  
Control Group ◽  
Protective Effects ◽  
Barrier Dysfunction ◽  
Entire Study ◽  
Intestinal Barrier Dysfunction

Background/Aims: Let-7b was dramatically reduced after a dicer knockout of mice with intestinal barrier function injuries. This paper aims to investigate the molecular mechanism of let-7b by targeting p38 MAPK in preventing intestinal barrier dysfunction. Methods: A total of 186 patients were enrolled, with 93 in the control group and 93 in the PRO group. Only 158 patients completed the entire study, whereas the others either did not meet the inclusion criteria or refused to participate. To further verify the role of let-7b, intestinal epithelial conditional knockout (IKO) mice of mmu-let-7b model were established. Serum let-7b, zonulin, IL-6, and TNF-α concentrations were measured by ELISA or quantitative RT-PCR. Permeability assay was done by ussing chamber. The apoptotic cells were identified using an In Situ Cell Death Detection Kit. Protein was detected by western blot. Results: Probiotics can lower infection-related complications, as well as increase the serum and tissue let-7b levels. P38 MAPK was identified as the target of let-7b, as verified by NCM460 cells. P38 MAPK expression was increased, whereas tight-junction (TJ) proteins were significantly decreased in let-7b IKO mice (both P<0.05). Negative regulation of p38 MAPK molecular signaling pathways was involved in the protective effects of let-7b on intestinal barrier function. Conclusion: Let-7b was identified as a novel diagnosis biomarker or a potential treatment target for preventing intestinal barrier dysfunction.

scholarly journals Staphylococcal Enterotoxin A Induces Intestinal Barrier Dysfunction and Activates NLRP3 Inflammasome via NF-κB/MAPK Signaling Pathways in Mice

Toxins ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 29
Author(s):  
Chunmei Liu ◽  
Kunmei Chi ◽  
Meng Yang ◽  
Na Guo
Keyword(s):  
Signaling Pathways ◽  
Nlrp3 Inflammasome ◽  
Intestinal Barrier ◽  
Mapk Signaling ◽  
Staphylococcal Enterotoxin ◽  
Foodborne Diseases ◽  
Staphylococcal Enterotoxin A ◽  
Barrier Dysfunction ◽  
Intestinal Barrier Dysfunction ◽  
Mapk Signaling Pathways

Staphylococcal enterotoxin A (SEA), the toxin protein secreted by Staphylococcus aureus, can cause staphylococcal food poisoning outbreaks and seriously threaten global public health. However, little is known about the pathogenesis of SEA in staphylococcal foodborne diseases. In this study, the effect of SEA on intestinal barrier injury and NLRP3 inflammasome activation was investigated by exposing BALB/c mice to SEA with increasing doses and a potential toxic mechanism was elucidated. Our findings suggested that SEA exposure provoked villi injury and suppressed the expression of ZO-1 and occludin proteins, thereby inducing intestinal barrier dysfunction and small intestinal injury in mice. Concurrently, SEA significantly up-regulated the expression of NLRP3 inflammasome-associated proteins and triggered the mitogen-activated protein kinase (MAPK) and nuclear factor kappa-B (NF-κB) signaling pathways in jejunum tissues. Notably, selective inhibitors of MAPKs and NF-κB p65 ameliorated the activation of NLRP3 inflammasome stimulated by SEA, which further indicated that SEA could activate NLRP3 inflammasome through NF-κB/MAPK pathways. In summary, SEA was first confirmed to induce intestinal barrier dysfunction and activate NLRP3 inflammasome via NF-κB/MAPK signaling pathways. These findings will contribute to a more comprehensive understanding of the pathogenesis of SEA and related drug-screening for the treatment and prevention of bacteriotoxin-caused foodborne diseases via targeting specific pathways.

scholarly journals Coral-Derived Endophytic Fungal Product, Butyrolactone-I, Alleviates Lps Induced Intestinal Epithelial Cell Inflammatory Response Through TLR4/NF-κB and MAPK Signaling Pathways: An in vitro and in vivo Studies

2021 ◽  
Vol 8 ◽  
Author(s):  
Shengwei Chen ◽  
Yi Zhang ◽  
Xueting Niu ◽  
Sahar Ghulam Mohyuddin ◽  
Jiayin Wen ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Tight Junction ◽  
Signaling Pathway ◽  
Inflammatory Responses ◽  
Intestinal Barrier ◽  
Mapk Signaling ◽  
In Vivo Studies ◽  
Protective Effects ◽  
Tnf Α ◽  
Junction Protein

Herein, we assessed the anti-inflammatory and intestinal barrier protective effects of butyrolactone-I (BTL-1), derived from the coral-derived endophytic fungus (Aspergillus terreus), using the LPS-induced IPEC-J2 inflammation model and the DSS-induced IBD model in mice. In IPEC-J2 cells, pretreatment with BTL-I significantly inhibited TLR4/NF-κB signaling pathway and JNK phosphorylation, resulting in the decrease of IL-1β and IL-6 expression. Interestingly, BTL-1 pretreatment activated the phosphorylation of ERK and P38, which significantly enhanced the expression of TNF-α. Meanwhile, BTL-1 pretreatment upregulated tight junction protein expression (ZO-1, occludin, and claudin-1) and maintained intestinal barrier and intestinal permeability integrity. In mice, BTL-1 significantly alleviated the intestinal inflammatory response induced by DSS, inhibited TLR4/NF-κB signaling pathway, and MAPK signaling pathway, thus reducing the production of IL-1, IL-6, and TNF-α. Further, the expression of tight junction proteins (ZO-1, occludin, and claudin-1) was upregulated in BTL-1 administrated mice. Therefore, it has been suggested that butyrolactone-I alleviates inflammatory responses in LPS-stimulated IPEC-J2 and DSS-induced murine colitis by TLR4/NF-κB and MAPK signal pathway. Thereby, BTL-1 might potentially be used as an ocean drug to prevent intestinal bowel disease.

scholarly journals Dietary Taxifolin Protects Against Dextran Sulfate Sodium-Induced Colitis via NF-κB Signaling, Enhancing Intestinal Barrier and Modulating Gut Microbiota

2021 ◽  
Vol 11 ◽  
Author(s):  
Jinxiu Hou ◽  
Mingyang Hu ◽  
Le Zhang ◽  
Ya Gao ◽  
Libao Ma ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Immunoglobulin A ◽  
Intestinal Barrier ◽  
Mapk Signaling ◽  
Protective Effects ◽  
Gut Health ◽  
Beneficial Effects ◽  
Rdna Sequencing

Taxifolin is a natural antioxidant polyphenol with various bioactivities and has many beneficial effects on human gut health. However, little is known of its function on colitis. In this study, the protective effects of taxifolin on colitis symptoms, inflammation, signaling pathways, and colon microbiota were investigated using dextran sulfate sodium (DSS)-induced colitis mice. Intriguingly, pre-administration of taxifolin alleviated the colitis symptoms and histological changes of the DSS-challenged mice. Supplementation of taxifolin significantly inhibited the secretions of tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 and significantly increased the secretions of IL-10, secretory immunoglobulin A, superoxide dismutase, and immunoglobulins (IgA, IgG, and IgM) in DSS-induced colitis mice. In addition, the activation of nuclear factor kappa B (NF-κB; p65 and IκBα) signaling was significantly suppressed by taxifolin supplementation. The expression of tight junction proteins (claudin-1 and occludin) was significantly increased by taxifolin. Moreover, 16S rDNA sequencing revealed that the DSS-induced changes of colon microbiota composition and microbial functions (amino acid metabolism and MAPK signaling) were restored by taxifolin, including the decreases of the abundances of Bacteroides, Clostridium ramosum, Clostridium saccharogumia, Sphingobacterium multivorum, and the ratio of Bacteroidetes/Firmicutes, and the increases of the abundances of Desulfovibrio C21 c20 and Gemmiger formicilis at species level. In conclusion, these results revealed that dietary taxifolin has a great potential to prevent colitis by inhibiting the NF-κB signaling pathway, enhancing intestinal barrier, and modulating gut microbiota.

Koumine Alleviates Lipopolysaccharide-Induced Intestinal Barrier Dysfunction in IPEC-J2 Cells by Regulating Nrf2/NF-κB Pathway

2020 ◽  
Vol 48 (01) ◽  
pp. 127-142 ◽  
Author(s):  
Jing Wu ◽  
Cheng-Lin Yang ◽  
Yuan-Kun Sha ◽  
Yong Wu ◽  
Zhao-Ying Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nuclear Translocation ◽  
Cell Monolayer ◽  
Intestinal Barrier ◽  
Inflammatory Factors ◽  
Growth Promoter ◽  
Protective Effects ◽  
Barrier Dysfunction ◽  
Intestinal Barrier Dysfunction ◽  
Junction Proteins

Gelsemium elegans Benth. (G. elegans), a traditional Chinese medicine, has great potential as an effective growth promoter in animals, however, the mechanism of its actin remains unclear. Here, we evaluated the protective effects of koumine extract from G. elegans against lipopolysaccharide (LPS)-induced intestinal barrier dysfunction in IPEC-J2 cells through alleviation of inflammation and oxidative stress. MTT and LDH assays revealed that koumine significantly reduced LPS cytotoxicity. Transepithelial electrical resistance (TEER) and cell monolayer permeability assays showed that koumine treatment attenuated the LPS-induced intestinal barrier dysfunction with no particularly different effects in tight junction proteins such as ZO-1, claudin-1, and occludin. LPS-triggered inflammatory response was also suppressed by koumine, as evidenced by the downregulated inflammatory factors, including TNF-[Formula: see text], IL-6, IL-1[Formula: see text], NO, iNOS, and COX-2, which was closely connected with the inhibition of NF-[Formula: see text]B pathway for the decrease of phosphorylation of I[Formula: see text]B[Formula: see text] and NF-[Formula: see text]B and nuclear translocation of p-p65. Amount of reactive oxygen species (ROS) and MDA induced by LPS was also reduced by koumine through activation of Nrf2 pathway, and increased in the levels of Nrf2 and HO-1 degradation of keap-1 to promote anti-oxidants, including superoxide dismutase (SOD) and catalase (CAT). To summarize, koumine-reduced the oxidative stress and inflammatory reaction triggered by LPS through regulation of the Nrf2/NF-[Formula: see text]B signaling pathway and preventing intestinal barrier dysfunction.

scholarly journals Enterocyte-specific epidermal growth factor prevents barrier dysfunction and improves mortality in murine peritonitis

2009 ◽  
Vol 297 (3) ◽  
pp. G471-G479 ◽  
Author(s):  
Jessica A. Clark ◽  
Heng Gan ◽  
Alexandr J. Samocha ◽  
Amy C. Fox ◽  
Timothy G. Buchman ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Intestinal Permeability ◽  
Cecal Ligation ◽  
Intestinal Barrier ◽  
Protective Effects ◽  
Barrier Dysfunction ◽  
Intestinal Barrier Dysfunction ◽  
Septic Peritonitis ◽  
Epidermal Growth

Systemic administration of epidermal growth factor (EGF) decreases mortality in a murine model of septic peritonitis. Although EGF can have direct healing effects on the intestinal mucosa, it is unknown whether the benefits of systemic EGF in peritonitis are mediated through the intestine. Here, we demonstrate that enterocyte-specific overexpression of EGF is sufficient to prevent intestinal barrier dysfunction and improve survival in peritonitis. Transgenic FVB/N mice that overexpress EGF exclusively in enterocytes ( IFABP-EGF) and wild-type (WT) mice were subjected to either sham laparotomy or cecal ligation and puncture (CLP). Intestinal permeability, expression of the tight junction proteins claudins-1, -2, -3, -4, -5, -7, and -8, occludin, and zonula occludens-1; villus length; intestinal epithelial proliferation; and epithelial apoptosis were evaluated. A separate cohort of mice was followed for survival. Peritonitis induced a threefold increase in intestinal permeability in WT mice. This was associated with increased claudin-2 expression and a change in subcellular localization. Permeability decreased to basal levels in IFABP-EGF septic mice, and claudin-2 expression and localization were similar to those of sham animals. Claudin-4 expression was decreased following CLP but was not different between WT septic mice and IFABP-EGF septic mice. Peritonitis-induced decreases in villus length and proliferation and increases in apoptosis seen in WT septic mice did not occur in IFABP-EGF septic mice. IFABP-EGF mice had improved 7-day mortality compared with WT septic mice (6% vs. 64%). Since enterocyte-specific overexpression of EGF is sufficient to prevent peritonitis-induced intestinal barrier dysfunction and confers a survival advantage, the protective effects of systemic EGF in septic peritonitis appear to be mediated in an intestine-specific fashion.

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