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

Author(s):  
Yue Chen ◽  
Lei Qiao ◽  
Xiaofan Song ◽  
Li Ma ◽  
Xina Dou ◽  
...  

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.

2021 ◽  
Author(s):  
Narae Kim ◽  
Min jeong Gu ◽  
Yoon-Chul Kye ◽  
Young-Jun Ju ◽  
Rira Hong ◽  
...  

Abstract Bacteriophages have long been used as a potential alternative to antibiotics for livestock due to their ability to specifically kill ETEC, which are a major cause of diarrhea in piglets. However, the control of ETEC infection by phages within intestinal epithelial cells, and their relationship with host immune responses, remain poorly understood. In this study, we evaluated the effect of phage EK99P-1 against ETEC K99-infected IPEC-J2. Phage EK99P-1 prevented ETEC K99-induced barrier disruption by attenuating the increased permeability mediated by the loss of tight junction proteins such as ZO-1, occludin, and claudin-3. ETEC K99-induced inflammatory responses, such as IL-8 secretion, were decreased by treatment with phage EK99P-1. We used a IPEC-J2/PBMC Transwell co-culture system to investigate whether the modulation of barrier disruption and chemokine secretion by phage EK99P-1 in ETEC K99-infected IPEC-J2 would influence basolateral immune cells. The results showed that phage EK99P-1 reduced the mRNA expression of ETEC K99-induced pro-inflammatory cytokines, IL-1β and IL-8, from PBMC collected on the basolateral side. Together, these results suggest that phage EK99P-1 prevented ETEC K99-induced barrier dysfunction in IPEC-J2 and alleviated inflammation caused by ETEC K99 infection. Reinforcement of the intestinal barrier by phage EK99P-1 also modulates the immune cell inflammatory response.


2014 ◽  
Vol 82 (7) ◽  
pp. 2913-2922 ◽  
Author(s):  
Arne M. Taxt ◽  
Yuleima Diaz ◽  
Amélie Bacle ◽  
Cédric Grauffel ◽  
Nathalie Reuter ◽  
...  

ABSTRACTEnterotoxigenicEscherichia coli(ETEC) expressing the heat-stable toxin (ST) (human-type [STh] and porcine-type [STp] variants) is among the five most important enteric pathogens in young children living in low- and middle-income countries. ST mediates diarrheal disease through activation of the guanylate cyclase C (GC-C) receptor and is an attractive vaccine target with the potential to confer protection against a wide range of ETEC strains. However, immunological cross-reactivity to the endogenous GC-C ligands guanylin and uroguanylin is a major concern because of the similarities to ST in amino acid sequence, structure, and function. We have investigated the presence of similar epitopes on STh, STp, guanylin, and uroguanylin by analyzing these peptides in eight distinct competitive enzyme-linked immunosorbent assays (ELISAs). A fraction (27%) of a polyclonal anti-STh antibody and an anti-STh monoclonal antibody (MAb) cross-reacted with uroguanylin, the latter with a 73-fold-lower affinity. In contrast, none of the antibodies raised against STp, one polyclonal antibody and three MAbs, cross-reacted with the endogenous peptides. Antibodies raised against guanylin and uroguanylin showed partial cross-reactivity with the ST peptides. Our results demonstrate, for the first time, that immunological cross-reactions between ST and the endogenous peptides can occur. However, the partial nature and low affinity of the observed cross-reactions suggest that the risk of adverse effects from a future ST vaccine may be low. Furthermore, our results suggest that this risk may be reduced or eliminated by basing an ST immunogen on STp or a selectively mutated variant of STh.


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