Search

Intestinal diseases often stem from a compromised intestinal barrier. This barrier relies on a functional epithelium and proper turnover of intestinal cells, supported by mitochondrial health. Mitochondria and lysosomes play key roles in cellular balance. Our previous researches indicate that biogenic selenium nanoparticles (SeNPs) can alleviate intestinal epithelial barrier damage by enhancing mitochondria-lysosome crosstalk, though the detailed mechanism is unclear. This study aimed to investigate the role of mitochondria-lysosome crosstalk in the protective effect of SeNPs on intestinal barrier function in mice exposed to lipopolysaccharide (LPS). The results showed that LPS exposure increased intestinal permeability in mice, leding to structural and functional damage to mitochondrial and lysosomal. Oral administration of SeNPs significantly upregulated the expression levels of TBC1D15 and Fis1, downregulated the expression levels of Rab7, Caspase-3, Cathepsin B, and MCOLN2, effectively alleviated LPS-induced mitochondrial and lysosomal dysfunction and maintained the intestinal barrier integrity in mice. Furthermore, SeNPs notably inhibited mitophagy caused by adenovirus-associated virus (AAV)-mediated RNA interference the expression of TBC1D15 in the intestine of mice, maintained mitochondrial and lysosomal homeostasis, and effectively alleviated intestinal barrier damage. These results suggested that SeNPs can regulate mitochondria-lysosome crosstalk and inhibit its damage by regulating the TBC1D15/Fis1/Rab7- signaling pathway. thereby alleviating intestinal barrier damage. It lays a theoretical foundation for elucidating the mechanism of mitochondria-lysosome crosstalk in regulating intestinal barrier damage and repair, and provides new ideas and new ways to establish safe and efficient nutritional regulation strategies to prevent and treat intestinal diseases caused by inflammation. [Display omitted] • Mitochondrial and lysosomal dysfunction can lead to intestinal barrier damage. • SeNPs regulates mitochondria-lysosome crosstalk to alleviate intestinal damage. • SeNPs regulate mitochondrial-lysosomal crosstalk by TBC1D15/Rab7 signal pathway. [ABSTRACT FROM AUTHOR]

Deoxynivalenol (DON), a secondary product of Fusarium metabolism, is common in wheat, corn, barley and other grain crops, posing a variety of adverse effects to environment, food safety, human and animal health. The absorption of DON mainly occurs in the proximal part of the small intestine, which can induce intestinal mucosal epithelial injury, and ultimately affect the growth performance and production performance of animals. This study was conducted to investigate the protective effects of selenium nanoparticles (SeNPs) - enriched Lactobacillus casei ATCC 393 (L. casei ATCC 393) on intestinal barrier function of C57BL/6 mice exposed to DON and its association with endoplasmic reticulum stress (ERS) and gut microbiota. The results showed that DON exposure increased the levels of interleukin-6 (IL-6) and interleukin-8 (IL-8), decreased the levels of interleukin-10 (IL-10) and transforming growth factor beta (TGF-β), caused a redox imbalance and intestinal barrier dysfunction, decreased the mRNA levels of endoplasmic reticulum- resident selenoproteins, activated ERS-protein kinase R-like endoplasmic reticulum kinase (PERK) signaling pathway, altered the composition of the gut microbiota and decreased short-chain fatty acids (SCFAs) content. Dietary supplementation with SeNPs-enriched L. casei ATCC 393 can effectively protect the integrity of intestinal barrier function by reducing inflammatory response, enhancing the antioxidant capacity, up-regulating the mRNA levels of endoplasmic reticulum-resident selenoproteins, inhibiting the activation of PERK signaling pathway, reversing gut microbiota dysbiosis and increasing the content of SCFAs in mice exposed to DON. In conclusion, dietary supplementation with SeNPs-enriched L. casei ATCC 393 effectively alleviated intestinal barrier dysfunction induced by DON in C57BL/6 mice, which may be closely associated with the regulation of ERS and gut microbiota. [Display omitted] • DON exposure caused endoplasmic reticulum stress and intestinal barrier injury. • Dietary SeNPs-enriched Lactobacillus casei ATCC 393 alleviated DON-induced intestinal barrier dysfunction. • The mechanism may be associated with the regulatory effects on endoplasmic reticulum stress and gut microbiota [ABSTRACT FROM AUTHOR]

The intestinal epithelial barrier plays a crucial role in maintaining human and animal health. Deoxynivalenol (DON) is a mycotoxin that contaminates cereal-based foods worldwide, which is a serious threat to human and animal health. This study was aimed to investigate the protective effect of selenium nanoparticles (SeNPs) synthesized by Lactobacillus casei ATCC 393 against DON-induced intestinal epithelial barrier dysfunction and its relationship with PERK-mediated signaling pathway. IPEC-J2 cells were randomly assigned to four groups: Con (vehicle), DON (0.6 μg DON/mL, 48 h), SeNPs+DON (8 μg Se/mL, 24 h; 0.6 μg DON/mL, 48 h) and SeNPs (8 μg Se/mL, 24 h). Compared with Con group, the transepithelial electrical resistance (TEER) and the tight junction proteins expression of IPEC-J2 cells exposed to DON was increased and decreased, respectively. In addition, DON exposure led to increased ROS content, decreased antioxidant capacity, structural damage of endoplasmic reticulum (ER), and activation of endoplasmic reticulum stress (ERS)-related protein kinase R-like endoplasmic reticulum kinase (PERK) pathway in IPEC-J2. Compared with SeNPs+DON group, SeNPs alleviated oxidative stress, ER structure damage and PERK pathway activation and the increase of intestinal epithelial permeability of IPEC-J2 cells exposed to DON. PERK agonist (CCT020312) and inhibitor (GSK2656157) treatments were performed to identify the role of PERK signaling pathway in the regulatory effects of SeNPs on DON-induced intestinal epithelial barrier dysfunction. Compared with SeNPs+DON group, PERK agonist increased the expression levels of p-PERK. PERK inhibitor exerted a similar inhibitory effect to SeNPs on the p-PERK expression. In conclusion, SeNPs effectively alleviate DON-induced intestinal epithelial barrier dysfunction in IPEC-J2 cells, which are closely associated with ERS-related PERK signaling pathway. This will provide a potential solution for prevention and control of DON in the aquaculture industry. [Display omitted] • DON exposure caused endoplasmic reticulum stress and intestinal epithelial barrier damage in IPEC-J2 cells. • SeNPs alleviated DON-induced intestinal epithelial barrier damage in IPEC-J2 cells. • The mechanism is associated with the regulatory effects on endoplasmic reticulum stress-related PERK signaling pathway. [ABSTRACT FROM AUTHOR]

Mast cells play a crucial role in gastrointestinal physiology and pathophysiology. This study was conducted to investigate the role of mast cells (MCs) in the protective effect of Lactobacillus casei ATCC 393 (L. casei ATCC 393) on intestinal barrier function. The regulatory effect of L. casei ATCC 393 on intestinal barrier dysfunction and MCs activation induced by Enterotoxigenic Escherichia coli K88 (ETEC K88) were evaluated by porcine mucosal mast cells (PMMCs)-porcine jejunal epithelial cells (IPEC-J2)- L. casei ATCC 393 co-culture experiments in vitro and MCs stabilizer drug experiment in vivo. Results showed that L. casei ATCC 393 pretreatment effectively alleviated the reduction of cell viability and increase of permeability in ETEC K88-infected IPEC-J2 cells. L. casei ATCC 393 pretreatment inhibited the increase of proinflammatory cytokines and some other MCs mediators, and decrease of anti-inflammatory cytokines in ETEC K88-infected PMMCs. Cromolyn sodium or L. casei ATCC 393 prevented ETEC K88-induced increase of intestinal epithelial cell permeability in IPEC-J2 cells when co-cultivation with PMMCs. Furthermore, cromolyn sodium or L. casei ATCC 393 pretreatment attenuated ETEC K88-induced increase of MCs mediators, mast cell proteases (MCPs) and carboxypeptidase A3 (CPA3) mRNA levels, and down-regulation of tight junction proteins, Toll-like receptor 2 and 4 (TLR2 and TLR4) expression levels in mice challenged by ETEC K88. These results indicated that intestinal barrier dysfunction caused by ETEC K88 was mediated by intestinal mast cell activation which can be prevented by L. casei ATCC 393 via TLRs signaling pathway. [ABSTRACT FROM AUTHOR]