Previous administration of recombinant or wild type Lactococcus lactis NCDO2118 prevented severe mucositis in mice

Mucositis is an inflammatory ulcerative condition that affects the mucous membranes of the entire gastrointestinal tract caused by anti-cancer chemotherapy. In the search for strategies to prevent or control this condition,many probiotic bacteria have been described as promising therapeutic tools. However, giving live bacteria during gut inflammatory conditions is a clinical concern and preventive treatments are the most suitable design namely when the disease onset is known as in the case of chemotherapy-induced mucositis. In the present study, we tested the effects of Lactococcus lactis NCDO2118 and Hsp65-producing L. lactis as a previous treatment to modulate intestinal mucosa immunity and prevent mucositis. Bacteria were given orally in a water bottle for four days. After ten days of the last treatment day, mucositis was induced. The results showed that pretreatment with either recombinant Hsp65-producing or wild type L. lactis NCDO2118 reduced intestinal permeability, preserved proteins of the junctional complex, and consequently controlled bacteria translocation. Pretreatment prevented the augment of inflammatory cells involved in mucositis pathogenesis, showing reduction in inflammation mediated by a favorable balance between cytokines. Furthermore, treatment of mice with recombinant or wild type L. lactis for four days modulated the gut microbiota contributing to intestinal homeostasis and to mucositis prevention. Together, our data showed that Hsp65-producing L. lactis and wild type L. lactis administered 10 days before disease induction had long-lasting immunoregulatory effects on mucositis. It provides an alternative therapeutic tool for mucositis that would avoid the risk of administering live bacteria during intestinal inflammation.