Abstract
Clostridioides difficile infection (CDI) is frequently associated with intestinal injury and mucosal barrier dysfunction, leading to an inflammatory response involving neutrophil localization and upregulation of pro-inflammatory cytokines. The severity of clinical manifestations is associated with the extent of the immune response, which requires mitigation for better clinical management. Probiotics could play a protective role in this disorder due to their immunomodulatory ability in gastrointestinal disorders. We assessed five single-strain and three multi-strain probiotics for their ability to modulate CDI fecal water (FW)-induced effects on T84 cells. The CDI-FW significantly (p < 0.05) decreased T84 cell viability. The CDI-FW-exposed cells also exhibited increased pro-inflammatory cytokine production as characterized by interleukin (IL)-8, C-X-C motif chemokine 5, macrophage inhibitory factor (MIF), IL-32, and tumor necrosis factor (TNF) ligand superfamily member 8. Probiotics were associated with strain-specific attenuation of the CDI-FW mediated effects, whereby Saccharomyces boulardii CNCM I-1079 and Lacticaseibacillus rhamnosus R0011 were most effective in reducing pro-inflammatory cytokine production and in increasing T84 cell viability. ProtecFlor™, Lactobacillus helveticus R0052, and Bifidobacterium longum R0175 showed moderate effectiveness, and L. rhamnosus GG R0343 along with the two other multi-strain combinations were the least effective. Overall, the findings showed that probiotic strains possess the capability to modulate the CDI-mediated inflammatory response in the gut lumen.
Highlights
Clostridioides infection (CDI) is a toxin-mediated intestinal disease that is the most frequently identified cause of healthcare-associated infectious diarrhea (Awad et al, 2014)
In the cells treated with CDIFW containing the probiotic treatments L. rhamnosus R0011 and S. boulardii CNCM I-1079, cell viability was significantly (p < 0.05) higher in comparison to the Clostridioides difficile infection (CDI)-fecal water (FW) blank sample (Figure 1)
While the roles of both IL-8 and CXCL5 in CDI pathophysiology have been previously documented (El Feghaly et al, 2013a), this study shows a potential role of TNFSRF8, IL-32, and macrophage inhibitory factor (MIF) in CDI-mediated inflammation
Summary
Clostridioides (formerly Clostridium difficile) infection (CDI) is a toxin-mediated intestinal disease that is the most frequently identified cause of healthcare-associated infectious diarrhea (Awad et al, 2014). The pathogenesis of CDI is strongly associated with the production of enterotoxin A (TcdA) and enterotoxin B and the presence of other virulence factors such as S-layer proteins and flagellin (Thelestam and Chaves-Olarte, 2000; Ausiello et al, 2006; Stevenson et al, 2015) These factors enable C. difficile to induce an acute inflammatory response in intestinal cells, resulting in neutrophil activation and recruitment that lead to intestinal epithelial damage (Chaves-Olarte et al, 1997; Brito et al, 2002). A recent study on human and murine CDI found that assessing multiple inflammatory serum markers can better predict adverse outcomes as compared to the currently used methods of predicting CDI mortality (Dieterle et al, 2020) Inflammatory markers such as procalcitonin and hepatocyte growth factor were found to be the best predictor for disease severity, and IL-8, CXCL5, CXCL10, and IL-2Rα were the best predictors of 30-day mortality (Dieterle et al, 2020). The mitigation of CDI-mediated inflammation could play an important role in regulating the host immune response, leading to better management of CDI outcomes (Kelly and Kyne, 2011)
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