Evaluation of new pharmacological and probiotic approaches for the treatment of fibrosis in inflammatory bowel disease

Intestinal fibrosis is a common complication of Inflammatory bowel disease (IBD), and the underlying mechanism of its pathogenesis remains incompletely understood. Intestinal fibrosis develops due to ongoing tissue damage and is closely linked to chronic inflammation. It is, in fact, a frequent complication in patients with Crohn’s Disease (CD), with more than 50% of patients experiencing complications such as stenosis and fistulae due to the progression of fibrosis. While understanding the mechanisms of IBD-related inflammation is moving forward and potential treatment options are emerging, effective and safe drugs for treating the fibrosis associated with IBD remain lacking, underscoring the urgent need to explore new strategies to address fibrosis and improve patient outcomes. Recent evidence suggests that probiotics may provide novel strategies to counteract fibrotic processes. In this study, the potential of a multi-strain probiotic formulation, OxxySlabTM, to counteract key processes involved in intestinal fibrosis was evaluated using in vitro models of intestinal fibrosis and epithelial-mesenchymal transition (EMT). Specifically, the differentiation of intestinal fibroblasts into activated myofibroblasts was examined using CCD-18Co cells, while EMT was examined using Caco-2 cells differentiated into intestinal epithelial cells (IECs); both processes were induced by transforming growth factor-β1 (TGF-β1). Treatment with the multi-strain probiotic formulation decreases cell proliferation and modulates fibrosis-related markers, as assessed by CCK-8 assay and MTT assay, Western blotting, and immunofluorescence. The multi-strain probiotic lysate inhibited both canonical and non-canonical TGF-β1 signalling pathways, and it also reduced TGF-β1 gene expression in activated myofibroblasts, as shown by RT-qPCR. Moreover, probiotic administration has been shown to reverse EMT by restoring epithelial markers and downregulating mesenchymal markers. These preliminary results highlight the beneficial effects of the OxxySlab as an adjunctive therapeutic agent targeting key pathways involved in intestinal fibrosis.