| dc.description.abstract | 5-Fluouracil (5-FU) is a chemotherapy widely used for different types of cancer. Due
to the non-selectivity of this drug, different side effects may appear in patients
undergoing therapy, such as intestinal mucositis. This condition is characterized by
inflammation and ulceration of the gastrointestinal mucosa, and so far there are no
curative treatments, but only guidelines related to palliative interventions that seek to
improve the quality of life of patients. The use of probiotics has been considered an
important therapeutic strategy for the treatment of mucositis, and the bacterium
Akkermansia muciniphila has stood out due to its anti-inflammatory and
immunomodulatory properties. Therefore, the objective of this work was to evaluate
the probiotic effect of A. muciniphila BAA 835 in a murine model of intestinal mucositis
induced by 5-FU. Initially, the dose-response effect, bacterial viability and the best
treatment protocol were evaluated. Subsequently, the other clinical, microbiological,
immunological, histological and physiological parameters were analyzed. For this,
Balb/c mice with mucositis induced with 5-FU (300 mg/Kg), in a single intraperitoneal
dose, were used. Our results suggest that the best dose of probiotic was 109 CFU, in
its viable form and under a preventive protocol, since in these conditions attenuation
of weight loss and reduction of intestinal length was observed, in addition to the
decrease in MPO and EPO levels in the tissue. Following this treatment protocol, no
statistical differences were observed in the food consumption of the treated animals;
however, there was a significant improvement in the clinical parameters measured
using the daily disease activity index (DAI). The probiotic also improved the integrity of
the epithelial barrier, decreasing intestinal permeability and bacterial translocation, in
addition to contributing to the preservation of the architecture of the intestine, and
attenuation of the loss of goblet cells. A. muciniphila also contributed to decreased the
levels of enterobacteria in the intestine and expansion of lactic acid bacteria. In
addition, a significant increase in the levels of sIgA, circulating lymphocytes, cytokine
IL10, and reduction of IL6, IL1β, TNF, circulating neutrophils, hydroperoxides and the
enzyme superoxide dismutase in the tissue were demonstrated. Therefore, oral
administration of A. muciniphila was able to attenuate the damage caused by mucositis
induced by 5-FU. | |
