Weissella cibaria Attenuated LPS-Induced Dysfunction of Intestinal Epithelial Barrier in a Caco-2 Cell Monolayer Model.

Liping Huang,Ning Yao,Kang Cui,Zhen Li,Wang Ma,Wenhao Mao,Huan Zhao,Yurong Du

doi:10.3389/fmicb.2020.02039

Abstract

The dysfunction of the intestinal epithelial barrier contributes to local or systemic infection and inflammation. Some lactic acid bacteria (LAB) strains had been shown to improve the conditions of barrier function and, for this reason, are recognized as probiotics. Weissella cibaria, a species belonging to the LAB group, is known to promote several health benefits. However, the role of W. cibaria in regulating the integrity of the intestinal epithelial barrier has not yet been investigated. In this study, W. cibaria MW01 was isolated from Chinese sauerkraut and was selected based on its functional features, such as gastric juice and bile salt tolerance, besides antagonistic activity against pathogenic bacteria. In a cellular model of the intestinal barrier, it was observed that W. cibaria was able to adhere more efficiently than Lactobacillus rhamnosus GG in Caco-2 cells. Moreover, the LPS-induced inflammation in Caco-2 cells was attenuated by the treatment with W. cibaria MW01, which reduced the synthesis of TNF-α, IL-6, and IL-8. In addition, it was noted that the treatment with W. cibaria MW01 recovered the integrity of the Caco-2 cell monolayer exposed to LPS. Furthermore, W. cibaria MW01 significantly alleviated LPS-induced downregulation of tight junction proteins (TJP) (claudin, occludin, and tight junction protein-1). Mechanistically, W. cibaria MW01 inhibited the translocation of NF-κB to the nucleus and deactivated the MLCK-pMLC pathway during LPS exposure. Thus, W. cibaria MW01, as a potential probiotic, can protect intestinal epithelial barrier function by regulating inflammation and expression of TJP via the NF-κB-mediated MLCK-pMLC pathway.

Highlights

The intestinal epithelial barrier, which is composed of the intestinal epithelium, is a tight physical barrier between the mucosal and luminal environments
W. cibaria MW01 treatment reduced the activation of the MLCK-pMLC signaling pathway induced by LPS (Figure 6C). These results suggested that W. cibaria MW01 may play its beneficial effects by modulating the inflammatory responses and the expression of tight junctions (TJ) proteins through the NF-κB-mediated MLCK-pMLC signaling pathway
Four W. cibaria strains were isolated from sauerkraut in Northeast China, which showed tolerance to artificial and bile salts, indicating that they may survive in the harsh conditions of the gastrointestinal environment

Summary

Introduction

The intestinal epithelial barrier, which is composed of the intestinal epithelium, is a tight physical barrier between the mucosal and luminal environments. TJ dysfunction has been related to an impaired epithelial barrier function, supporting gut leakage that allows bacterial translocation and entry of antigens and toxins to the internal milieu of the body (Citi, 2018). As results, this scenario is favorable to the occurrence and progression of various severe diseases, including inflammatory bowel disease (IBD) (Luissint et al, 2016; Buckley and Turner, 2018), metabolic syndrome (Carratu et al, 1999; Groschwitz and Hogan, 2009), and systemic infection complications (Manfredo Vieira et al, 2018; Khalaf and Sokol, 2020). Regulating TJ proteins to maintain the integrity of the intestinal epithelial barrier may be an effective therapeutic or prophylactic approach to ameliorate the conditions of diseases associated with intestinal barrier disruption (Ulluwishewa et al, 2011; Duan et al, 2019)

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Results

Conclusion