AUTHOR=Sato Nana , Garcia-Castillo Valeria , Yuzawa Mao , Islam Md. Aminul , Albarracin Leonardo , Tomokiyo Mikado , Ikeda-Ohtsubo Wakako , Garcia-Cancino Apolinaria , Takahashi Hideki , Villena Julio , Kitazawa Haruki 

TITLE=Immunobiotic Lactobacillus jensenii TL2937 Alleviates Dextran Sodium Sulfate-Induced Colitis by Differentially Modulating the Transcriptomic Response of Intestinal Epithelial Cells

JOURNAL=Frontiers in Immunology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.02174

DOI=10.3389/fimmu.2020.02174

ISSN=1664-3224

ABSTRACT=<p>Immunobiotics have emerged as a promising intervention to alleviate intestinal damage in inflammatory bowel disease (IBD). However, the beneficial properties of immunobiotics are strain dependent and, therefore, each strain has to be evaluated in order to demonstrate its potential application in IBD. Our previous <italic>in vitro</italic> and <italic>in vivo</italic> studies demonstrated that <italic>Lactobacillus jensenii</italic> TL2937 attenuates gut acute inflammatory response triggered by Toll-like receptor 4 activation. However, its effect on colitis has not been evaluated before. In this work, we studied whether the TL2937 strain was able to protect against the development of colitis in a dextran sodium sulfate (DSS)-induced mouse model and we delved into the mechanisms of action by evaluating the effect of the immunobiotic bacteria on the transcriptomic response of DSS-challenged intestinal epithelial cells. <italic>L. jensenii</italic> TL2937 was administered to adult BALB/c mice before the induction of colitis by the administration of DSS. Colitis and the associated inflammatory response were evaluated for 14 days. Mice fed with <italic>L. jensenii</italic> TL2937 had lower disease activity index and alterations of colon length when compared to control mice. Reduced myeloperoxidase activity, lower production of pro-inflammatory (TNF-α, IL-1, CXCL1, MCP-1, IL-15, and IL-17), and higher levels of immunoregulatory (IL-10 and IL-27) cytokines were found in the colon of TL2937-treated mice. In addition, the treatment of porcine intestinal epithelial (PIE) cells with <italic>L. jensenii</italic> TL2937 before the challenge with DSS differentially regulated the activation of the JNK pathway, leading to an increase in epithelial cell integrity and to a differential immunotranscriptomic response. TL2937-treated PIE cells had a significant reduction in the expression of inflammatory cytokines (<italic>TNF</italic>-α, <italic>IL-1</italic>α, <italic>IL-1</italic>β, <italic>IL-6, IL-15</italic>), chemokines (<italic>CCL2, CCL4, CCL8, CXCL4, CXCL5, CXCL9, CXCL10</italic>), adhesion molecules (<italic>SELE, SELL, EPCAM</italic>), and other immune factors (<italic>NCF1, NCF2, NOS2, SAA2</italic>) when compared to control cells after the challenge with DSS. The findings of this work indicate that (a) <italic>L. jensenii</italic> TL2937 is able to alleviate DSS-induced colitis suggesting a potential novel application for this immunobiotic strain, (b) the modulation of the transcriptomic response of intestinal epithelial cells would play a key role in the beneficial effects of the TL2937 strain on colitis, and (c) the <italic>in vitro</italic> PIE cell immunoassay system could be of value for the screening and selection of new immunobiotic strains for their application in IBD.</p>