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

Abstract

Clostridioides difficile is a major cause of diarrhea in patients with antibiotic administration. Lacticaseibacillus casei T21, isolated from a human gastric biopsy, was tested in a murine C. difficile infection (CDI) model and colonic epithelial cells (Caco-2 and HT-29). Daily administration of L. casei T21 [1 × 108 colony forming units (CFU)/dose] for 4 days starting at 1 day before C. difficile 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 L. casei T21 exerted biological activities that fight against C. difficile as demonstrated in colonic epithelial cells by the following: (i) suppression of gene expression and production of IL-8, an important chemokine involved in C. difficile pathogenesis, (ii) reduction in the expression of SLC11A1 (solute carrier family 11 member 1) and HuR (human antigen R), important genes for the lethality of C. difficile toxin B, (iii) augmentation of intestinal integrity, and (iv) up-regulation of MUC2, a mucosal protective gene. These results supported the therapeutic potential of L. casei T21 for CDI and the need for further study on the intervention capabilities of CDI.

Lactobacillus spp. for Gastrointestinal Health: Current and Future Perspectives

“…Lactobacillus species are believed to enhance intestinal barrier defence by promoting mucus secretion. In vitro studies have demonstrated that conditioned media from L. casei T21 can up-regulate the mucosal protective MUC2 gene in colonic epithelial cells (Caco2 and HT29) challenged with C. difficile ( 35 ). Although it has been proposed that acid may stimulate enteric cells to produce mucins ( 36 ) incubating HT29 cells with lactic acid did not replicate these findings indicating that other substances secreted by L. casei T21 are responsible for the increased gene expression.…”

Enhanced Bacteremia in Dextran Sulfate-Induced Colitis in Splenectomy Mice Correlates with Gut Dysbiosis and LPS Tolerance

“…Intestinal inflammation or severe systemic inflammation can cause leaky gut through the direct damage on tight junctions (such as hypoxia and inflammatory cells) and/or indirect injuries from enhanced intestinal pathogenic organisms (gut dysbiosis) [18,19]. Beneficial bacteria in the gut are important for normal gut integrity due to several factors, including (i) the production of short-chain fatty acids (an energy source of enterocytes) by intestinal fermentation of indigestible foods [20] and (ii) the regulation of pathogenic bacteria, partly through competition for nutrients [21]. As a result, gut dysbiosis can lead to a gut barrier defect [15].…”

Uremia-Induced Gut Barrier Defect in 5/6 Nephrectomized Mice Is Worsened by Candida Administration through a Synergy of Uremic Toxin, Lipopolysaccharide, and (1➔3)-β-D-Glucan, but Is Attenuated by Lacticaseibacillus rhamnosus L34

“…and Clostridium spp. ), the dominant, primarily Gram-positive, anaerobes in the healthy condition [ 40 ] ( Figure 3 E). In parallel, the non-metric multidimensional scaling (NMDS), the pairwise dissimilarity between groups that the distance from axis representing the ranks of data [ 35 ], identified Anaerovorax spp.…”