Browsing by Subject "Diarrhea"

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    Saccharomyces boulardii CNCM I-745 supernatant improves markers of gut barrier function and inflammatory response in small intestinal organoids
    (2025) Filipe Rosa, Louisa; Gonda, Steffen; Roese, Nadine; Bischoff, Stephan C.; Lachowicz-Wiśniewska, Sabina
    Objectives: Saccharomyces boulardii CNCM I-745, a probiotic yeast, is effectively used for the treatment of acute diarrhea as well as for the prevention and treatment of traveller‘s diarrhea and diarrhea under tube feeding. The underlying mechanisms are not fully elucidated. Both antitoxic and regulatory effects on the intestinal barrier, mediated either by the yeast or yeast-derived substrates, have been discussed. Methods: To examine the effects of Saccharomyces boulardii released substrates (S.b.S) on gastrointestinal (GI) barrier function, a murine small intestinal organoid cell model under stress was used. Stress was induced by lipopolysaccharide (LPS) exposure or withdrawal of growth factors from cell culture medium (GFRed). Stressed organoids were treated with S.b.S (200 µg/mL), and markers of GI barrier and inflammatory response were assessed. Results: GFRed-induced stress was characterized by disturbances in selected tight junction (TJ) (p < 0.05), adherent junction (AJ) (p < 0.001), and mucin (Muc) formation (p < 0.01), measured by gene expressions, whereby additional S.b.S treatment was found to reverse these effects by increasing Muc2 (from 0.22 to 0.97-fold change, p < 0.05), Occludin (Ocln) (from 0.37 to 3.5-fold change, p < 0.0001), and Claudin (Cldn)7 expression (from 0.13 ± 0.066-fold change, p < 0.05) and by decreasing Muc1, Cldn2, Cldn5, and junctional adhesion molecule A (JAM-A) expression (all p < 0.01). Further, S.b.S normalized expression of nucleotide binding oligomerization domain (Nod)2- (from 44.5 to 0.51, p < 0.0001) and matrix metalloproteinase (Mmp)7-dependent activation (from 28.3 to 0.02875 ± 0.0044 ** p < 0.01) of antimicrobial peptide defense and reduced the expression of several inflammatory markers, such as myeloid differentiation primary response 88 (Myd88) (p < 0.01), tumor necrosis factor α (Tnfα) (p < 0.01), interleukin (IL)-6 (p < 0.01), and IL-1β (p < 0.001). Conclusions: Our data provide new insights into the molecular mechanisms by which Saccharomyces boulardii CNCM I-745-derived secretome attenuates inflammatory responses and restores GI barrier function in small intestinal organoids.
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    Tannic acid and ethacridine lactate attenuate markers of stress-induced intestinal barrier dysfunctions in murine small intestinal organoids
    (2025) Filipe Rosa, Louisa; Gonda, Steffen; Roese, Nadine; Bischoff, Stephan C.; Kwok, Hang Fai (Henry); Alaimo, Alessandro
    (1) Background: Tannacomp® is a drug consisting of tannin albuminate, a complex of tannic acid (TA) and ethacridine lactate (Eta) used for treating acute and traveler’s diarrhea. TA is thought to modulate gastrointestinal barrier function, but the underlying mechanisms and whether Eta has similar effects remains unclear. (2) Methods: to investigate the effects of TA and Eta on the intestinal barrier, stress responses were induced in murine intestinal organoids by lipopolysaccharide (LPS) exposure or withdrawal of growth factors from cell culture medium (GFRed). Further, organoids were exposed to either TA (0.01 mg/mL) or Eta (0.002 mg/mL) and markers of inflammatory response and gut barrier function were assessed. (3) Results: TA and Eta reduced several inflammatory markers such as interleukin 6, interleukin 1β, tumor necrosis factor α, and myeloid differentiation primary response 88 in stressed organoids. In addition, TA and Eta attenuated LPS- and GFRed-mediated gut barrier dysfunctions, with normalization of tight junction, adherent junction and mucin gene expression and reduction of Nod2- and matrix metalloproteinase 7-dependent activation of antimicrobial peptides. (4) Conclusions: our data show that TA and Eta modulate markers of inflammation and the intestinal barrier and suggest novel mechanisms of action of this drug that could broaden its treatment indications.