Abstract
Mucositis is a clinically important gastrointestinal inflammatory infirmity, generated by antineoplastic drugs cytotoxic effects. The inflammatory process caused by this disease frequently leads to derangements in the alimentary tract and great malaise for the patient. Novel strategies are necessary for its prevention or treatment, as currently available treatments of mucositis have several limitations in relieving its symptoms. In this context, several research groups have investigated the use of probiotic bacteria, and in particular dairy bacterial strains. Compelling evidences reveal that milk fermented by certain probiotic bacteria has the capacity to ameliorate intestinal inflammatory disorders. In addition, innovative probiotic delivery strategies, based on probiotics incorporation into protective matrices, such as whey proteins, were able to increase the therapeutic effect of probiotic strains by providing extra protection for bacteria against environmental stresses. Therefore, in this study, we evaluated the role of the whey protein isolate (WPI), when added to skim milk fermented by Lactobacillus casei BL23 (L. casei BL23) or by Propionibacterium freudenreichii CIRM-BIA138 (P. freudenreichii 138), as a protective matrix against in vitro stress challenges. In addition, we investigated the therapeutic effect of these fermented beverages in a murine model of mucositis induced by 5-Fluorouracil (5-FU). Our results demonstrated that milk supplementation with 30% (w/v) of WPI increases the survival rate of both strains when challenged with acid, bile salts, high temperature and cold storage stresses, compared to fermented skim milk without the addition of WPI. Moreover, treatment with the probiotic beverages prevented weight loss and intestinal damages in mice receiving 5-FU. We conclude that the presence of WPI maximizes the anti-inflammatory effects of L. casei BL23, but not for P. freudenreichii 138, suggesting that whey protein enhancement of probiotic activity might be strain-dependent.
Highlights
Mucositis is a severe inflammation that affects the entire extension of the Alimentary Tract (AT) of individuals undergoing malignancy treatment based on chemotherapy or radiotherapy (Sonis, 2004)
We observed a significant increase in the colony forming unit (CFU) counting of L. casei BL23 when cultivated in SMLC after 24 h (6.3 × 109 CFU mL−1), in comparison with MRS medium (2.1 × 109 CFU mL−1)
The survival was further increased when SMLC was supplemented with 30% whey protein isolate (WPI), leading to the highest survival rate of L. casei BL23 (80.6%)
Summary
Mucositis is a severe inflammation that affects the entire extension of the Alimentary Tract (AT) of individuals undergoing malignancy treatment based on chemotherapy or radiotherapy (Sonis, 2004). One of the main drugs associated with this condition is 5-Fluorouracil (5-FU) This is a antimetabolic drug commonly prescribed for the treatment of head, neck and gastrointestinal cancer (Longley et al, 2003). Mucositis is characterized by pathological changes in the small bowel These changes include the presence of degenerate enterocytes (Ciorba et al, 2016), submucosal vessel damage, leukocyte infiltrate in the lamina propria, with accumulation of neutrophils and eosinophils (Antunes et al, 2016), increased mucin production and degeneration of goblet cells (Stringer, 2013), atrophy of villi, hypoplasia and apoptosis of intestinal crypts (Chang et al, 2012). There has been a growing interest in the use of probiotics as promising candidates for the treatment of this disease (Carvalho et al, 2017a)
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