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.