Intranasal or oral Lactobacilli administration: Which one is best for fighting against Pseudomonas aeruginosa (PA) respiratory tract infections?

Abstract

In CF patients, PA chronic lung infections combined with acquisition of antibiotics resistance leads to therapeutic deadlock. Among non-antibiotic alternative, the use of Lactobacilli is promising since its oral administration (OA) stimulates immune system, decreases nosocomial pneumonia & CF exacerbations incidence. IntranasaI administration (IA) stimulates respiratory immunity & modifies lung architecture. Screened from a collection of 50 CF patients expectorations, 3 Lactobacillus ( L. paracasei Lp, L. salivarius Ls & L. brevis Lb ) respiratory strains were identified for its anti-PA properties in vitro . Selected strains were tested, alone or cocktail (Lpsb, Lsb) for preventive effect in a murine model of acute PA pneumonia. Lactobacillus GG was used as a control. IA & OA of Lactobacillus strains (10 6 CFU/mice) 18 h prior to PA infection (10 6 CFU/mice) was evaluated in 12 groups of C57BL/6 mice (Lpsb, Lsb, Lp, Ls, Lb, PA, Lpsb + PA, Lp + PA, Ls + PA, Lb + PA, Lsb + PA, LGG + PA) & 3 groups (Lsb, Lsb + PA, LGG + PA) respectively. At 24 h PA post-infection (pi), lung & serum were collected for bacterial counts & cytokines analysis. The Lpsb cocktail increased the survival rate to 7 days (100% P < 0.001) compared to PA group (11.7%). Lactobacillus treatment decreased the PA lung load 24 h pi compared to PA group with a higher effect for Lpsb, Lsb , Ls & Lb group (reduction > 1log 10 P < 0.05). Interestingly, our Lactobacillus strains had better anti-PA properties than the LGG strain & its IA led to a better reduction of PA lung load 24 h pi than OA. Preventive Lactobacillus treatment decreased proinflammatory cytokines. This study demonstrated the better protective efficacy of live Lactobacillus IA vs OA against murine PA pneumonia. Mechanistic approaches are under progress. L. salivarius & L. brevis are promising beneficial strains in the context of lung infection in CF.