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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.

Keywords: Clostridioides difficile; Lacticaseibacillus casei T21; gut dysbiosis; inflammation; probiotics; proinflammatory cytokines; toxin lethality.

Research Insights

SupplementHealth OutcomeEffect TypeEffect Size
Lacticaseibacillus caseiImproved Intestinal IntegrityBeneficial
Moderate
Lacticaseibacillus caseiIncreased MUC-2 ExpressionBeneficial
Moderate
Lacticaseibacillus caseiReduced Body Weight LossBeneficial
Moderate
Lacticaseibacillus caseiReduced Diarrhea IncidenceBeneficial
Moderate
Lacticaseibacillus caseiReduced DysbiosisBeneficial
Large
Lacticaseibacillus caseiReduced Expression of Lethal Toxin GenesBeneficial
Moderate
Lacticaseibacillus caseiReduced Hospital Mortality RateBeneficial
Large
Lacticaseibacillus caseiReduced Intestinal Pathology ChangesBeneficial
Moderate
Lacticaseibacillus caseiReduced Intestinal PermeabilityBeneficial
Moderate
Lacticaseibacillus caseiReduced Pro-inflammatory Cytokine ReleaseBeneficial
Moderate
Lacticaseibacillus casei R0215Improved Gut IntegrityBeneficial
Moderate
Lacticaseibacillus casei R0215Increased Mucin ProductionBeneficial
Moderate
Lacticaseibacillus casei R0215Reduced Body Weight LossBeneficial
Moderate
Lacticaseibacillus casei R0215Reduced Diarrhea IncidenceBeneficial
Moderate
Lacticaseibacillus casei R0215Reduced DysbiosisBeneficial
Large
Lacticaseibacillus casei R0215Reduced Gut LeakageBeneficial
Moderate
Lacticaseibacillus casei R0215Reduced Hospital Mortality RateBeneficial
Large
Lacticaseibacillus casei R0215Reduced Intestinal Pathology ChangesBeneficial
Moderate
Lacticaseibacillus casei R0215Reduced Pro-inflammatory Cytokine LevelsBeneficial
Moderate
Lactobacillus casei R0215Improved Intestinal Integrity in Colonic Epithelial CellsBeneficial
Moderate
Lactobacillus casei R0215Increased MUC2 Gene Expression in Colonic Epithelial CellsBeneficial
Moderate
Lactobacillus casei R0215Reduced DiarrheaBeneficial
Large
Lactobacillus casei R0215Reduced Gut LeakageBeneficial
Moderate
Lactobacillus casei R0215Reduced Intestinal PathologyBeneficial
Moderate
Lactobacillus casei R0215Reduced Pro-inflammatory Cytokines in CDI Mouse ModelBeneficial
Moderate
Lactobacillus casei R0215Reduced Weight Loss in Clostridioides difficile Infection Murine ModelBeneficial
Large

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