Biogenic selenium nanoparticles alleviate intestinal barrier injury in mice through TBC1D15/Fis1/Rab7 pathway.

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.

Targeting mitochondria with antioxidant nutrients for the prevention and treatment of postweaning diarrhea in piglets.

Post-weaning diarrhea (PWD) in piglets poses a significant challenge and presents a grave threat to the global swine industry, resulting in considerable financial losses and compromising the welfare of animals. PWD is commonly associated with gut homeostatic imbalance, including oxidative stress, excessive inflammation, and microbiota dysbiosis. Antibiotic use has historically been a common initiative to combat PWD, but concerns about the development of antibiotic resistance have led to increased interest in alternative strategies. Mitochondria are key players in maintaining cellular homeostasis, and their dysfunction is intricately linked to the onset and progression of PWD. Accumulating evidence suggests that targeting mitochondrial function using antioxidant nutrients, such as vitamins, minerals and polyphenolic compounds, may represent a promising approach for preventing and treating PWD. Moreover, nutrients based on antioxidant strategies have been shown to improve mitochondrial function, restore intestinal redox balance, and reduce oxidative damage, which is a key driver of PWD. The present review begins with an overview of the potential interplay between mitochondria and gut homeostasis in the pathogenesis of PWD in piglets. Subsequently, alternative strategies to prevent and treat PWD using antioxidant nutrients to target mitochondria are described and discussed. Ultimately, we delve into potential limitations and suggest future research directions in this field for further advancement. Overall, targeting mitochondria using antioxidant nutrients may be a promising approach to combat PWD and provides a potential nutrition intervention strategy for regulating gut homeostasis of weaned piglets.

Replacing dietary sodium selenite with biogenic selenium nanoparticles improves the growth performance and gut health of early-weaned piglets.

Selenium nanoparticles (SeNPs) are proposed as a safer and more effective selenium delivery system than sodium selenite (Na2SeO3). Here, we investigated the effects of replacing dietary Na2SeO3 with SeNPs synthesized by Lactobacillus casei ATCC 393 on the growth performance and gut health of early-weaned piglets. Seventy-two piglets (Duroc × Landrace × Large Yorkshire) weaned at 21 d of age were divided into the control group (basal diet containing 0.3 mg Se/kg from Na2SeO3) and SeNPs group (basal diet containing 0.3 mg Se/kg from SeNPs) during a 14-d feeding period. The results revealed that SeNPs supplementation increased the average daily gain (P = 0.022) and average daily feed intake (P = 0.033), reduced (P = 0.056) the diarrhea incidence, and improved (P = 0.013) the feed conversion ratio compared with Na2SeO3. Additionally, SeNPs increased jejunal microvilli height (P = 0.006) and alleviated the intestinal barrier dysfunction by upregulating (P < 0.05) the expression levels of mucin 2 and tight junction proteins, increasing (P < 0.05) Se availability, and maintaining mitochondrial structure and function, thereby improving antioxidant capacity and immunity. Furthermore, metabolomics showed that SeNPs can regulate lipid metabolism and participate in the synthesis, secretion and action of parathyroid hormone, proximal tubule bicarbonate reclamation and tricarboxylic acid cycle. Moreover, SeNPs increased (P < 0.05) the abundance of Holdemanella and the levels of acetate and propionate. Correlation analysis suggested that Holdemanella was closely associated with the regulatory effects of SeNPs on early-weaned piglets through participating in lipid metabolism. Overall, replacing dietary Na2SeO3 with biogenic SeNPs could be a potential nutritional intervention strategy to prevent early-weaning syndrome in piglets.

Selenium nanoparticles alleviate deoxynivalenol-induced intestinal epithelial barrier dysfunction by regulating endoplasmic reticulum stress in IPEC-J2 cells.

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.

Lactobacillus casei ATCC 393 combined with vasoactive intestinal peptide alleviates dextran sodium sulfate-induced ulcerative colitis in C57BL/6 mice via NF-κB and Nrf2 signaling pathways.

Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) which is related to an immunological imbalance of the intestinal mucosa. Many clinical evidences indicate probiotics supplementation appears to be effective and safe in patients with UC. Vasoactive intestinal peptide (VIP) is an endogenous neuropeptide with multiple physiological and pathological effects. In this study, we investigated the protective effect of the combination of Lactobacillus casei ATCC 393 (L. casei ATCC 393) with VIP on dextran sodium sulfate (DSS)-induced UC in mice and the potential mechanism. The results showed that, compared with the control group, DSS treatment significantly shortened the colon length, caused inflammation and oxidative stress, and further resulted in the intestinal barrier dysfunction and gut microbiota dysbiosis. In addition, intervention with L. casei ATCC 393, VIP or L. casei ATCC 393 combined with VIP significantly reduced UC disease activity index. However, compared with L. casei ATCC 393 or VIP, L. casei ATCC 393 combined with VIP effectively relieved symptoms of UC by regulating immune response, enhancing antioxidant capacity, and regulating nuclear factor kappa-B (NF-κB) and nuclear factor erythroid-derived-2-like 2 (Nrf2) signaling pathways. In conclusion, this study suggests that L. casei ATCC 393 combined with VIP can effectively relieve DSS-induced UC, which is a promising treatment strategy for UC.

Biogenic selenium nanoparticles alleviate intestinal epithelial barrier injury by regulating mitochondria-lysosome crosstalk.

The intestinal epithelial barrier plays a fundamental role in human and animal health. Mitochondrial dysfunction can lead to intestinal epithelial barrier damage. The interaction between mitochondria and lysosomes has been proved to regulate each other's dynamics. Our previous studies have demonstrated that biogenic selenium nanoparticles (SeNPs) can alleviate intestinal epithelial barrier injury through regulating mitochondrial autophagy. In this study, we hypothesize that the protective effects of SeNPs against intestinal epithelial barrier dysfunction are associated with mitochondrial-lysosomal crosstalk. The results showed that lipopolysaccharide (LPS) and TBC1D15 siRNA transfection both caused the increase of intestinal epithelial permeability, activation of mitophagy, and mitochondrial and lysosomal dysfunction in porcine jejunal epithelial cells (IPEC-J2). SeNP pretreatment significantly up-regulated the expression levels of TBC1D15 and Fis1, down-regulated Rab7, caspase-3, MCOLN2 and cathepsin B expression levels, reduced cytoplasmic Ca2+ concentration, effectively alleviated mitochondrial and lysosomal dysfunction, and maintained the integrity of the intestinal epithelial barrier in IPEC-J2 cells exposed to LPS. Furthermore, SeNPs obviously reduced cytoplasmic Ca2+ concentration and activated the TBC1D15/Fis/Rab7-mediated signaling pathway, shortened the contact time between mitochondria and lysosomes, inhibited mitophagy, maintained mitochondrial and lysosomal homeostasis, and effectively attenuated intestinal epithelial barrier injury in IPEC-J2 cells transfected with TBC1D15 siRNA. These results indicated that the protective effect of SeNPs on intestinal epithelial barrier injury is closely associated with the TBC1D15/Rab7-mediated mitochondria-lysosome crosstalk signaling pathway.

Selenite Bioremediation by Food-Grade Probiotic Lactobacillus casei ATCC 393: Insights from Proteomics Analysis.

Microorganisms capable of converting toxic selenite into elemental selenium (Se0) are considered an important and effective approach for bioremediation of Se contamination. In this study, we investigated the mechanism of reducing selenite to Se0 and forming Se nanoparticles (SeNPs) by food-grade probiotic Lactobacillus casei ATCC 393 (L. casei ATCC 393) through proteomics analysis. The results showed that selenite added during the exponential growth period of bacteria has the highest reduction efficiency, and 4.0 mM selenite decreased by nearly 95% within 72 h and formed protein-capped-SeNPs. Proteomics analysis revealed that selenite induced a significant increase in the expression of glutaredoxin, oxidoreductase, and ATP binding cassette (ABC) transporter, which can transport glutathione (GSH) and selenite. Selenite treatment significantly increased the CydC and CydD (putative cysteine and glutathione importer, ABC transporter) mRNA expression level, GSH content, and GSH reductase activity. Furthermore, supplementation with an additional GSH significantly increased the reduction rate of selenite, while GSH depletion significantly inhibited the reduction of selenite, indicating that GSH-mediated Painter-type reaction may be the main pathway of selenite reduction in L. casei ATCC 393. Moreover, nitrate reductase also participates in the reduction process of selenite, but it is not the primary factor. Overall, L. casei ATCC 393 effectively reduced selenite to SeNPs by GSH and nitrate reductase-mediated reduction pathway, and the GSH pathway played the decisive role, which provides an environmentally friendly biocatalyst for the bioremediation of Se contamination. IMPORTANCE Due to the high solubility and bioavailability of selenite, and its widespread use in industrial and agricultural production, it is easy to cause selenite to accumulate in the environment and reach toxic levels. Although the bacteria screened from special environments have high selenite tolerance, their safety has not been fully verified. It is necessary to screen out strains with selenite-reducing ability from nonpathogenic, functionally known, and widely used strains. Herein, we found food-grade probiotic L. casei ATCC 393 effectively reduced selenite to SeNPs by GSH and nitrate reductase-mediated reduction pathway, which provides an environmentally friendly biocatalyst for the bioremediation of Se contamination.

Biogenic Selenium Nanoparticles Synthesized by Lactobacillus casei ATCC 393 Alleviate Acute Hypobaric Hypoxia-Induced Intestinal Barrier Dysfunction in C57BL/6 Mice.

Exposure to hypobaric hypoxia at high altitude will cause different tissue and organ damage over a long period of time. Studies have shown that hypobaric hypoxia can cause severe primary intestinal barrier dysfunction, and then cause multiple organ dysfunction. Our previous research showed that selenium nanoparticles (SeNPs) synthesized by Lactobacillus casei ATCC 393 (L. casei ATCC 393) can effectively alleviate intestinal barrier dysfunction caused by oxidative stress and inflammation in mice. This study was conducted to investigate the protective effect of biological SeNPs synthesized by L. casei ATCC 393 on intestinal barrier function in acute hypobaric hypoxic stress mice. The results showed that compared with the hypobaric hypoxic, the SeNPs synthesized by L. casei ATCC 393 by oral administration could effectively alleviate the shortening of intestinal villi, which decreased the level of diamine oxidase (DAO) and myeloperoxidase (MPO), and the expression level of tight junction protein in ileum was increased. In addition, SeNPs significantly increased the activities of superoxide dismutase (SOD), cyclooxygenase (COX-1) and glutathione peroxidase (GPx), and decreased the level of malondialdehyde (MDA), and inhibit the increase of hypoxia related factor. SeNPs effectively regulate the intestinal microecology disorder caused by hypobaric hypoxia stress, and maintain the intestinal microecology balance. In addition, oral administration of SeNPs had better protective effect on intestinal barrier function of mice under hypobaric hypoxia stress. These results suggested that SeNPs synthesized by L. casei ATCC 393 can effectively alleviate the damage of intestinal barrier function under acute hypobaric hypoxic stress, which may be closely related to the antioxidant activity of SeNPs.

Biogenic Selenium Nanoparticles Attenuate Aß25-35-Induced Toxicity in PC12 Cells via Akt/CREB/BDNF Signaling Pathway.

Deposition of aggregated amyloid beta (Aß) protein is considered to be a major causative factor that is associated with the development of oxidative stress and neuroinflammation in the pathogenesis of Alzheimer's disease (AD). Selenium nanoparticles (SeNPs) have been experimentally using for treatment of neurological disease due to their low toxicity, high bioavailability, and multiple bioactivities. This study was conducted to investigate the protective effects of biogenic SeNPs by Lactobacillus casei ATCC 393 against Aß25-35-induced toxicity in PC12 cells and its association with oxidative stress and inflammation. The results showed that SeNPs had no cytotoxicity on PC12 cells. Moreover, SeNPs entered cells through cellular endocytosis, which effectively attenuated Aß25-35-induced toxicity in PC12 cells. In addition, compared with Aß25-35 model group, SeNP pretreatment significantly enhanced the antioxidant capacity, inhibited the overproduction of reactive oxygen species (ROS), effectively regulated the inflammatory response, decreased the activity of acetylcholinesterase, significantly reduced the expression level of caspase-1 and the ratio of Bcl-2/Bax, and upregulated the expression level of p53. Furthermore, compared with Aß25-35 model group, SeNPs effectively promoted the phosphorylation of Akt and cAMP-response element-binding protein (CREB), and upregulated the expression level of brain-derived neurotrophic factor (BDNF). In addition, the Akt inhibitor (AKT inhibitor VIII, AKTi-1/2) could reverse the protective effects of SeNPs on PC12 cells. The Akt agonist (SC79) had a similar effect on PC12 cells as that of SeNPs. Overall, this study demonstrated that biogenic SeNPs can effectively alleviate the Aß25-35-induced toxicity in PC12 cells via Akt/CREB/BDNF signaling pathway.

Dietary supplementation with selenium nanoparticles-enriched Lactobacillus casei ATCC 393 alleviates intestinal barrier dysfunction of mice exposed to deoxynivalenol by regulating endoplasmic reticulum stress and gut microbiota.

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-ß), 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.

Protective effect of biogenic selenium nanoparticles against diquat-induced acute toxicity via regulation of gut microbiota and its metabolites.

Selenium nanoparticles (SeNPs) with unique biological properties have been suggested as a safer and more effective platform for delivering of Selenium for biological needs. In this study, we investigated the association between gut microbiota altered by SeNPs supplementation and its metabolites under oxidative stress conditions through 16S rDNA gene sequencing analysis and untargeted metabolomics. The results showed that dietary supplementation with SeNPs attenuated diquat-induced acute toxicity in mice, as demonstrated by lower levels of inflammatory effector cells, and biochemical markers in serum such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN) and lactate dehydrogenase (LDH). SeNPs also reversed the perturbed gut microbiota composition induced by diquat, decreased the Firmicutes/Bacteroidetes ratio, and increased the abundance of beneficial bacteria such as Akkermansia, Muribaculaceae, Bacteroides and Parabacteroides. Untargeted fecal metabolomics showed that SeNPs can regulate the production of steroids and steroid derivatives, organonitrogen compounds, pyridines and derivatives and other metabolites. Microbiome-metabolome correlation analysis suggested that Parabacteroides was the key bacteria for the SeNPs intervention, which might upregulate the levels of metabolites such as trimethaphan, emedastine, berberine, desoxycortone, tetrahydrocortisone. This study demonstrated that dietary SeNPs supplementation can extensively modulate the gut microbiota and its metabolism, thereby alleviating diquat-induced acute toxicity.

Selenium Nanoparticles-Enriched Lactobacillus casei ATCC 393 Prevents Cognitive Dysfunction in Mice Through Modulating Microbiota-Gut-Brain Axis.

Purpose: The bidirectional communication between the gut and the central nervous system mediated by gut microbiota is closely related to the occurrence and development of neurodegenerative diseases, including Alzheimer's disease (AD). Selenium (Se) has been identified as playing a role against AD. Probiotics have beneficial effects on host brain function and behavior by modulating the microbiota-gut-brain axis. Herein, we evaluated the protective effects of Lactobacillus casei ATCC 393 (L. casei ATCC 393) and selenium nanoparticles-enriched L. casei ATCC 393 (L. casei ATCC 393-SeNPs) against D-galactose/aluminum chloride-induced AD model mice. Methods: The Morris Water Maze (MWM) test was used to assess cognitive function of mice. The morphology and histopathological changes, antioxidant capacity and immune responses in the brain and ileum were evaluated. The alterations in intestinal permeability of the mice were determined using FITC-dextran. Gut microbiota composition was assessed using 16s rRNA sequencing. Results: Thirteen weeks intervention with L. casei ATCC 393 or L. casei ATCC 393-SeNPs significantly improved cognitive dysfunction, and minimized amyloid beta (Aß) aggregation, hyperphosphorylation of TAU protein, and prevented neuronal death by modulating Akt/cAMP-response element binding protein (CREB)/brain-derived neurotrophic factor (BDNF) signaling pathway. Moreover, compared with L. casei ATCC 393, L. casei ATCC 393-SeNPs further effectively mitigated intestinal barrier dysfunction by improving antioxidant capacity, regulating immune response, restoring gut microbiota balance, and increasing the level of short-chain fatty acids and neurotransmitters, thereby inhibiting the activation of microglia and protecting brain neurons from neurotoxicity such as oxidative stress and neuroinflammation. Conclusion: These findings indicated that targeting the microbiota-gut-brain axis with L. casei ATCC 393-SeNPs may have therapeutic potential for the deficits of cognitive function in the AD model mice. Thus, we anticipate that L. casei ATCC 393-SeNPs may be a promising and safe Se nutritional supplement for use as a food additive to prevent the neurodegenerative disease.

Green synthesis of nanoparticles by probiotics and their application.

Nanoparticles (NPs), which have unique properties due to their extremely small size and high surface area to volume ratio, have attracted considerable attention and become an important tool for innovation in various fields. Traditionally, NPs are synthesized by physical and chemical processes, but these methods have high capital costs and energy demand, and involve the use of toxic and hazardous chemicals, which are prone to secondary pollution of the environment. In recent years, the use of microorganism-mediated methods has emerged as an alternative to traditional physical and chemical methods. The synthesis of NPs by microorganism has the advantages of non-toxicity, eco-friendliness, low-cost, reproducibility in production, easy amplification, and well-defined morphology. Probiotics are a kind of active microorganisms beneficial to the host. Compared with other microorganisms, probiotics are characterized by non-pathogenicity, rapid growth and regulation of gene expression, and produce a variety of proteins and enzymes involved in the synthesis of NPs. Therefore, the production of NPs using probiotics is an environmentally friendly and commercially attractive method, which provides new ideas and approaches for the application of NPs in the fields of biomedicine, agriculture and environmental remediation. This review aims to summarize the literature on the biosynthesis of NPs by probiotics and their synthetic mechanisms and applications.

Biogenic Selenium Nanoparticles Alleviate Intestinal Epithelial Barrier Damage through Regulating Endoplasmic Reticulum Stress-Mediated Mitophagy.

The intestinal barrier plays a fundamental role in body health. Intracellular redox imbalance can trigger endoplasmic reticulum stress (ERS) and mitophagy, leading to intestinal barrier damage. Our previous studies demonstrated that mitophagy is closely associated with the protective effects of biogenic selenium nanoparticles (SeNPs) on intestinal epithelial barrier function. Thus, we hypothesize that ERS and mitophagy are likely involved in the regulatory effects of SeNPs on oxidative stress-induced intestinal epithelial barrier dysfunction. The results showed that oxidative stress or ERS caused the increase of intestinal epithelial permeability. SeNPs effectively alleviated hydrogen peroxide (H2O2-)-induced structural damage of endoplasmic reticulum (ER) and mitochondria of porcine jejunal epithelial cells (IPEC-J2). SeNPs significantly decreased intracellular inositol triphosphate (IP3) and Ca2+ concentration, down-regulated inositol trisphosphate receptor (IP3R) expression level, and up-regulated ER-resident selenoproteins mRNA levels in IPEC-J2 cells exposed to H2O2. In addition, SeNPs pretreatment significantly decreased the intracellular Ca2+, IP3, IP3R, and reactive oxygen species (ROS) levels; protected the structure and function of ER and mitochondria; and effectively alleviated the increase of intestinal epithelial permeability of IPEC-J2 cells exposed to tunicamycin (TM). Moreover, SeNPs significantly inhibited the colocalization of mitochondria and lysosomes. Furthermore, compared with TM model group, SeNPs significantly inhibited the activation of PERK/eIF2α/ATF4 and AMPK/mTOR/PINK1 signaling pathway. The PERK agonist (CCT020312) and the AMPK agonist (AICAR) could reverse the protective effects of SeNPs on IPEC-J2 cells. The PERK inhibitor (GSK2656157) and the AMPK inhibitor (compound C) had a similar effect on IPEC-J2 cells as that of SeNPs. In summary, the protective effects of SeNPs on intestinal barrier dysfunction are closely associated with ERS-related PERK and mitophagy-related AMPK signaling pathway.

Dietary supplementation with biogenic selenium nanoparticles alleviate oxidative stress-induced intestinal barrier dysfunction.

Selenium (Se) is an essential micronutrient that promotes body health. Endemic Se deficiency is a major nutritional challenge worldwide. The low toxicity, high bioavailability, and unique properties of biogenic Se nanoparticles (SeNPs) allow them to be used as a therapeutic drug and Se nutritional supplement. This study was conducted to investigate the regulatory effects of dietary SeNPs supplementation on the oxidative stress-induced intestinal barrier dysfunction and its association with mitochondrial function and gut microbiota in mice. The effects of dietary SeNPs on intestinal barrier function and antioxidant capacity and its correlation with gut microbiota were further evaluated by a fecal microbiota transplantation experiment. The results showed that Se deficiency caused a redox imbalance, increased the levels of pro-inflammatory cytokines, altered the composition of the gut microbiota, and impaired mitochondrial structure and function, and intestinal barrier injury. Exogenous supplementation with biogenic SeNPs effectively alleviated diquat-induced intestinal barrier dysfunction by enhancing the antioxidant capacity, inhibiting the overproduction of reactive oxygen species (ROS), preventing the impairment of mitochondrial structure and function, regulating the immune response, maintaining intestinal microbiota homeostasis by regulating nuclear factor (erythroid-derived-2)-like 2 (Nrf2)-mediated NLR family pyrin domain containing 3 (NLRP3) signaling pathway. In addition, Se deficiency resulted in a gut microbiota phenotype that is more susceptible to diquat-induced intestinal barrier dysfunction. Supranutritional SeNPs intake can optimize the gut microbiota to protect against intestinal dysfunctions. This study demonstrates that dietary supplementation of SeNPs can prevent oxidative stress-induced intestinal barrier dysfunction through its regulation of mitochondria and gut microbiota.

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 ß-hexosaminidase (ß-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.

Lactobacillus casei ATCC 393 and it's metabolites alleviate dextran sulphate sodium-induced ulcerative colitis in mice through the NLRP3-(Caspase-1)/IL-1ß pathway.

Inflammatory bowel disease (IBD) represents a broad group of intestinal disorders, including ulcerative colitis (UC) and Crohn's disease (CD). Probiotics are increasingly being recognized as a means of treatment for people suffering from IBD. Our previous studies demonstrated that Lactobacillus casei ATCC 393 (L. casei ATCC 393) effectively alleviated enterotoxigenic Escherichia coli K88-induced intestinal barrier dysfunction. This study was conducted to investigate the protective effects of L. casei ATCC 393 and its metabolites on dextran sulfate sodium (DSS)-induced UC in C57BL/6 mice and the potential mechanism of these effects. The results showed that oral administration of L. casei ATCC 393 and its metabolites both effectively reversed the DSS-induced weight loss, and the reduction in the disease activity index (DAI), colon length, and villus height of colon tissue in mice. Compared to the DSS-induced model group, L. casei ATCC 393 and its metabolites significantly inhibited the infiltration of immune cells into the intestinal mucosa, decreased the production of pro-inflammatory factors, and increased the expression of anti-inflammatory factors in the serum and colon tissue, increased the expression levels of occludin, ZO-1, and claudin-1, and reduced the expression of nucleotide binding oligomeric domain-like receptor protein 3 (NLRP3), cysteine proteinase-1 (Caspase-1), IL-1ß, and IL-18. In addition, L. casei ATCC 393 and its metabolites effectively improved DSS-induced gut microbiota dysbiosis. These results suggested that L. casei ATCC 393 and its metabolites alleviated the DSS-induced ulcerative inflammatory response in C57BL/6 mice through the NLRP3-(Caspase-1)/IL-1ß signaling pathway.

Protective Effects of Selenium Nanoparticle-Enriched Lactococcus lactis NZ9000 against Enterotoxigenic Escherichia coli K88-Induced Intestinal Barrier Damage in Mice.

Composite microecological agents have received widespread attention due to their advantageous properties, including safety, multiple effects, and low cost. This study was conducted to evaluate the protective effects of selenium (Se) nanoparticle (SeNP)-enriched Lactococcus lactis NZ9000 (L. lactis NZ9000-SeNPs) against enterotoxigenic Escherichia coli (ETEC) K88-induced intestinal barrier damage in C57BL/6 mice. The oral administration of L. lactis NZ9000-SeNPs significantly increased the villus height and the number of goblet cells in the ileum; reduced the levels of serum and ileal interleukin-1ß (IL-1ß), tumor necrosis factor alpha (TNF-α), and interferon gamma (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 activation of the Toll-like receptor (TLR)/nuclear factor kappa B (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 a nutritionally essential trace element for humans and animals, is incorporated into selenoproteins that have a wide range of pleiotropic effects, ranging from antioxidant to anti-inflammatory effects. However, 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 substitution of sodium selenite applied in food, feed, and biomedicine.

Biogenic selenium nanoparticles by Lactobacillus casei ATCC 393 alleviate the intestinal permeability, mitochondrial dysfunction and mitophagy induced by oxidative stress.

Selenium (Se) is an essential trace element. Nano-selenium has attracted great attention due to its various biological properties, especially strong antioxidant activity, high bioavailability, and low toxicity. Our previous studies demonstrated that the selenium nanoparticles (SeNPs) synthesized by Lactobacillus casei ATCC 393 (L. casei ATCC 393) alleviate hydrogen peroxide (H2O2)-induced intestinal epithelial barrier dysfunction via the mitochondrial pathway. However, the mechanism of SeNPs exerting antioxidant activity through the mitochondrial pathway remains unclear. This study was conducted to investigate the role of mitophagy in the protective effects of SeNPs on H2O2-induced porcine intestinal epithelial cells against oxidative damage. The results showed that the SeNPs synthesized by L. casei ATCC 393 had no cytotoxicity on IPEC-J2 cells and effectively antagonized the cytotoxicity of 500 µM H2O2 on IPEC-J2 cells. Moreover, SeNPs attenuated the H2O2-induced intestinal epithelial barrier dysfunction and ROS overproduction, as well as alleviated the adenosine triphosphate (ATP) level and the mitochondrial membrane potential (MMP) decrease. In addition, compared to the oxidative stress model group, pretreatment with biogenic SeNPs significantly up-regulated the expression levels of occludin and claudin-1. Moreover, when compared to the oxidative stress model group, SeNPs inhibited the phosphorylation level of the mammalian target of rapamycin (m-TOR), as well as the expression levels of Unc-51-like kinase 1(ULK1), light chain 3 (LC3)-II/LC3-I, PTEN-induced kinase 1 (PINK1) and Parkin proteins. The fluorescence colocalization images of mitochondria and lysosomes demonstrated that SeNPs significantly reduced the fusion of mitochondria and lysosomes when compared to the oxidative stress model group. These results demonstrate that the SeNPs synthesized by L. casei ATCC 393 can effectively alleviate the H2O2-induced intestinal epithelial barrier dysfunction through regulating mTOR/PINK1-mediated mitophagy.

Preparation, characterization, and in vivo evaluation of anti-inflammatory activities of selenium nanoparticles synthesized by Kluyveromyces lactis GG799.

Selenium (Se) is an essential micronutrient that has implications in human diseases, including inflammatory bowel disease (IBD), especially with respect to Se deficiencies. Recently, selenium nanoparticles (SeNPs) have attracted significant attention due to their diversity of biological activities and unique advantages including low toxicity and high biological availability. In this study, an eco-friendly, efficient and low-cost method for synthesis of SeNPs by Kluyveromyces lactis GG799 (K. lactis GG799) was established, and the SeNPs were investigated for their physicochemical properties and anti-inflammatory activities in vivo. K. lactis GG799 was able to successfully transform sodium selenite into bright-red SeNPs with particle sizes of 80 and 150 nm and the nanoparticles accumulated intracellularly. Upon isolation, the SeNPs were found to be mainly capped by proteins and polysaccharides by components analysis. Dietary supplementation with 0.6 mg kg-1 Se (in the form of biogenic SeNPs) effectively attenuated dextran sulphate sodium (DSS)-induced ulcerative colitis (UC) in mice by alleviating oxidative stress and intestinal inflammation. These findings suggested that SeNPs synthesized by K. lactis GG799 may be a promising and safe Se supplement for the prevention and treatment of IBD.