1. Glucocorticoid-Induced Leucine Zipper Protein and Yeast-Extracted Compound Alleviate Colitis and Reduce Fungal Dysbiosis.
- Author
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Gentili M, Sabbatini S, Nunzi E, Lusenti E, Cari L, Mencacci A, Ballet N, Migliorati G, Riccardi C, Ronchetti S, and Monari C
- Subjects
- Animals, Mice, Mice, Inbred C57BL, Yeasts, Dextran Sulfate, Male, Intestinal Mucosa metabolism, Intestinal Mucosa microbiology, Intestinal Mucosa drug effects, Gastrointestinal Microbiome drug effects, Inflammatory Bowel Diseases microbiology, Inflammatory Bowel Diseases drug therapy, Inflammatory Bowel Diseases metabolism, Disease Models, Animal, Dysbiosis microbiology, Dysbiosis drug therapy, Colitis drug therapy, Colitis microbiology, Colitis metabolism, Colitis chemically induced, Transcription Factors metabolism
- Abstract
Inflammatory bowel diseases (IBD) have a complex, poorly understood pathogenesis and lack long-lasting effective treatments. Recent research suggests that intestinal fungal dysbiosis may play a role in IBD development. This study investigates the effects of the glucocorticoid-induced leucine zipper protein (GILZp)", known for its protective role in gut mucosa, and a yeast extract (Py) with prebiotic properties, either alone or combined, in DSS-induced colitis. Both treatments alleviated symptoms via overlapping or distinct mechanisms. In particular, they reduced the transcription levels of pro-inflammatory cytokines IL-1β and TNF-α, as well as the expression of the tight junction protein Claudin-2. Additionally, GILZp increased MUC2 transcription, while Py reduced IL-12p40 and IL-6 levels. Notably, both treatments were effective in restoring the intestinal burden of clinically important Candida and related species. Intestinal mycobiome analysis revealed that they were able to reduce colitis-associated fungal dysbiosis, and this effect was mainly the result of a decreased abundance of the Meyerozima genus, which was dominant in colitic mice. Overall, our results suggest that combined treatment regimens with GILZp and Py could represent a new strategy for the treatment of IBD by targeting multiple mechanisms, including the fungal dysbiosis.
- Published
- 2024
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