AUTHOR=Panpetch Wimonrat , Phuengmaung Pornpimol , Cheibchalard Thanya , Somboonna Naraporn , Leelahavanichkul Asada , Tumwasorn Somying 

TITLE=Lacticaseibacillus casei Strain T21 Attenuates Clostridioides difficile Infection in a Murine Model Through Reduction of Inflammation and Gut Dysbiosis With Decreased Toxin Lethality and Enhanced Mucin Production

JOURNAL=Frontiers in Microbiology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2021.745299

DOI=10.3389/fmicb.2021.745299

ISSN=1664-302X

ABSTRACT=<p><italic>Clostridioides difficile</italic> is a major cause of diarrhea in patients with antibiotic administration. <italic>Lacticaseibacillus casei</italic> T21, isolated from a human gastric biopsy, was tested in a murine <italic>C. difficile</italic> infection (CDI) model and colonic epithelial cells (Caco-2 and HT-29). Daily administration of <italic>L. casei</italic> T21 [1 × 10<sup>8</sup> colony forming units (CFU)/dose] for 4 days starting at 1 day before <italic>C. difficile</italic> challenge attenuated CDI as demonstrated by a reduction in mortality rate, weight loss, diarrhea, gut leakage, gut dysbiosis, intestinal pathology changes, and levels of pro-inflammatory cytokines [interleukin (IL)-1β, tumor necrosis factor (TNF)-α, macrophage inflammatory protein 2 (MIP-2), and keratinocyte chemoattractant (KC)] in the intestinal tissue and serum. Conditioned media from <italic>L. casei</italic> T21 exerted biological activities that fight against <italic>C. difficile</italic> as demonstrated in colonic epithelial cells by the following: (i) suppression of gene expression and production of IL-8, an important chemokine involved in <italic>C. difficile</italic> pathogenesis, (ii) reduction in the expression of <italic>SLC11A1</italic> (solute carrier family 11 member 1) and <italic>HuR</italic> (human antigen R), important genes for the lethality of <italic>C. difficile</italic> toxin B, (iii) augmentation of intestinal integrity, and (iv) up-regulation of <italic>MUC2</italic>, a mucosal protective gene. These results supported the therapeutic potential of <italic>L. casei</italic> T21 for CDI and the need for further study on the intervention capabilities of CDI.</p>