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

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE288972 | GEO | 2026/04/17

REPOSITORIES: GEO

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Project description:Lifestyle disorders like obesity, type 2 diabetes (T2D), and cardiovascular diseases can be prevented and treated by regular physical activity. During exercise, skeletal muscles release signaling factors that communicate with other organs and mediate beneficial effects of exercise. These factors include myokines, metabolites, and extracellular vesicles (EVs). In the present study, we have examined how electrical pulse stimulation (EPS) of myotubes, a model of exercise, affects the cargo of released EVs. Chronic low frequency EPS was applied for 24 h to human myotubes isolated and differentiated from biopsy samples from 6 morbidly obese females with T2D, and EVs, both exosomes and microvesicles (MV), were isolated from cell media 24 h thereafter. Size and concentration of EV subtypes were characterized by nanoparticle tracking analysis, surface markers were examined by flow cytometry and Western blotting, and morphology was confirmed by transmission electron microscopy. Protein content was assessed by high-resolution proteomic analysis (LC-MS/MS), non-coding RNA was quantified by Affymetrix microarray, and selected microRNAs (miRs) validated by real time RT-qPCR. The size and concentration of exosomes and MV were unaffected by EPS. Of the 400 miRs identified in the EVs, EPS significantly changed the level of 15 exosome miRs, of which miR-1233-5p showed the highest fold change. The miR pattern of MV was unaffected by EPS. Totally, about 1000 proteins were identified in exosomes and 2000 in MV. EPS changed the content of 73 proteins in exosomes, 97 in MVs, and of these 4 were changed in both exosomes and MV (GANAB, HSPA9, CNDP2, and ATP5B). By matching the EPS-changed miRs and proteins in exosomes, 31 targets were identified, and among these several promising signaling factors. Of particular interest were CNDP2, an enzyme that generates the appetite regulatory metabolite Lac-Phe, and miR-4433b-3p, which targets CNDP2. Several of the regulated miRs, such as miR-92b-5p, miR-320b, and miR-1233-5p might also mediate interesting signaling functions.

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

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