Limosilactobacillus reuteri-derived exopolysaccharides facilitate the repair of intestinal epithelium barrier compromised by chemotherapy exposure

A majority of patients undergoing chemotherapy treatment develop side effects that delay further cancer treatment. Antimetabolites, like 5 Fluorouracil (5 FU), are known to induce gut and oral inflammation, highlighting the importance of chemotherapy toxicity management. Here, we aimed to study whether probiotic bacterium Limosilactobacillus reuteri DSM 17938 (LR)-secreted components, including cell-free supernatant (CFS), exopolysaccharides (EPS), and extracellular membrane vesicles (MV), can improve gut barrier integrity following 5 FU exposure. Collectively, 5 FU altered the viability, metabolic activity, barrier integrity, and functional response of Caco-2 cells. EPS stimulation after 5 FU removal significantly improved the integrity and permeability of intestinal barrier through modulation of the transcriptional program associated with extracellular matrix and structure organization. Further, we found that CFS, MV and EPS differentially influenced monocyte polarization pathways, when monocytes were cultured with the supernatant from 5 FU exposed Caco-2 cells. Together, our findings suggest that the incorporation of bacterial metabolites, such as EPS, during chemotherapy could accelerate intestinal barrier recovery without suppressing the immune system, potentially allowing for a more effective scheduling of therapy in cancer patients.