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Effect of probiotic treatment (lactobacillus et/ou faecalibacterium prausnitzii) on radiation-induced colonic alterations and visceral hypersensitivity: improvment of the therapeutic efficency of mesenchymal stromal cell

Alexia Lapière has defended her thesis on 21th February 2020​ at IRSN, Fontenay-aux-Roses

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Research Unit > IRSN/PSE-SANTÉ/SERAMED/LRMed

Authors > LAPIERE Alexia

Publication Date > 21/02/2020

Summary

Cancers in the pelvic area are mostly treated by radiotherapy. Radiation of healthy tissues surrounding tumor leads to side effects years after the end of the treatment. Late onset of specific symptoms led to the definition of a new pathology, called Pelvic Radiation Disease (PRD), in 2010. Gastrointestinal dysfunctions observed in PRD considerably affect patient’s quality of life. These dysfunctions could be the consequence of a high inflammatory process induced in radiosensitive organs, as colon and rectum, after the rupture of intestinal barrier. It has been also showed changes in the intestinal microbiota diversity after radiotherapy. Indeed, Faecalibacterium prausnitzii (F. prausnitzii), which plays physiological key role in the colonic homeostasis, is decreased.

This thesis aim is to assess F. prausnitzii potential as a radio-protective agent for patients undergoing a pelvic radiotherapy, by preventing colonic injuries occurrence. We studied the effect of daily 109 CFU F. prausnitzii administration, 3 days, 7 days (short term) and 4 weeks (long term) after a 29Gy colorectal irradiation in a rat model. Colonic barrier integrity were assessed by in vivo and ex vivo colonic mucosa morphometric, histologic and immunohistologic analysis, and Ussing chamber method was used to evaluate functional ex vivo colonic permeability. Inflammatory parameters were studied by immunohistologic analysis of innate immune cells (neutrophils and macrophages) and by colonic mucosal cytokines assessment with ELISA method. F. prausnitzii treatment reduces radiation-induced colonic toxicity. Indeed, we reported a reduction of structural damages (3 days) and of ulceration length (7 days). Moreover, F. prausnitzii administration also reduces radiation-induced para-cellular permeability and neutrophils infiltration 3 days after irradiation.
It seems that F. prausnitzii therapeutic efficiency is due to specific activation of inflammatory response. IL-25 (IL-17E), a cytokine produced by tuft cells and IL-18, produced by epithelial cells, could also be involved in colonic protection process after irradiation. Long term F. prausnitzii administration (4 weeks), after having tested several administration modalities, didn’t show any therapeutic efficiency on radiation-induced structural damages. Based on our findings on short term therapeutic efficiency of F. prausnitzii, clinical application could be considered. Indeed, this new generation probiotic could reduce colorectal side effects and associated symptoms in pelvic radiotherapy patients, leading to a better tolerance of radiotherapy and a better quality of life.
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