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Acetate-producing Saccharomyces cerevisiae var. boulardii strains could exert improved effects on ulcerative colitis, which here, was preclinically evaluated in an acute dextran sodium sulphate induced model of colitis. Nine-week-old female mice were divided into 12 groups, receiving either drinking water or 2.75% dextran sodium sulphate for 7 days, combined with a daily gavage of various treatments with different levels of acetate accumulation: sham control (phosphate buffered saline, no acetate), non-probiotic control (Baker's yeast, no acetate), probiotic control (Enterol®, transient acetate), and additionally several Saccharomyces cerevisiae var. boulardii strains with respectively no, high, and extra-high acetate accumulation. Disease activity was monitored daily, and feces samples were collected at different timepoints. On day 14, the mice were sacrificed, upon which blood and colonic tissue were collected for analysis. Disease activity in inflamed mice was lower when treated with the high-acetate-producing strain compared to sham and non-probiotic controls. The non-acetate-producing strain showed higher disease activity compared to the acetate-producing strains. Accordingly, higher histologic inflammation was observed in non- or transient-acetate-producing strains compared to the sham control, whereas this increase was not observed for high- and extra-high-acetate-producing strains upon induction of inflammation. These anti-inflammatory findings were confirmed by transcriptomic analysis of differentially expressed genes. Moreover, only the strain with the highest acetate production was superior in maintaining a stable gut microbial alpha-diversity upon inflammation. These findings support new possibilities for acetate-mediated management of inflammation in inflammatory bowel disease by administrating high-acetate-producing Saccharomyces cerevisae var. boulardii strains. [ABSTRACT FROM AUTHOR]

Background: The consumption of ultra-processed foods has increased significantly worldwide and is associated with the rise in inflammatory bowel diseases. However, any causative factors and their underlying mechanisms are yet to be identified. This study aimed to further elucidate whether different types of the dietary emulsifier carrageenan (CGN) can alter the permeability and inflammatory state of the intestinal epithelium., Methods: Caco-2/HT29-MTX cocultures (n = 4) were exposed to either κ-, ι-, or λ-CGN (100 µg mL-1) for 24 hours. Organoid-derived monolayers from patients with Crohn's Disease (CD) were exposed to κ-CGN (100 µg mL-1) for 48 hours (n = 10). In both models, an inflamed condition was established by adding a mix of inflammatory stimuli. Changes in permeability were measured by transepithelial electrical resistance (TEER). In the organoid-derived monolayers, cytokines were quantified in the apical and basolateral supernatant and gene expression was analyzed with RT-qPCR., Results: None of the CGN subtypes altered permeability of non-inflamed or inflamed Caco-2/HT29-MTX cocultures. In organoid-derived monolayers, κ-CGN did not affect TEER, but induced alterations in the gene expression of tight junctions and mucus proteins. Expression of TNF, IL8, and IL1B increased upon κ-CGN stimulation, both in inflamed and non-inflamed monolayers. Cytokine release in the supernatant was increased by κ-CGN for IL-6, IL-13, IL-4, IL-2, and IL-10., Conclusions: Dietary CGN caused upregulation of inflammatory markers and affected cytokine release of intestinal epithelial cells from CD patients, while permeability remained unaltered. When inflammation was already present, this pro-inflammatory effect was more pronounced, suggesting a role for dietary CGN during active CD., (© 2024 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation.)