The Biotherapeutic Potential of Lactobacillus reuteri Characterized Using a Target-Specific Selection Process
Valeria Sagheddu, Francesca Uggeri, Luisella Belogi, Laura Remollino, Paola Brun, Giulia Bernabé, Giancarlo Moretti, Andrea Porzionato, Lorenzo Morelli, Ignazio Castagliuolo, Marina Elli
Abstract
The growing body of clinical and experimental data support the view that the efficacy of probiotics is strain-specific and disease-specific. Thus, newly isolated probiotic strains should be disease- targeted. Therefore, we firstly characterized a novel strain of Lactobacillus reuteri LMG P-27481 for safety (sensitivity to antibiotics and genome analysis) and putative efficacy (resistance to gut transit, adhesiveness, induction of cytokines, release of antimicrobial metabolites) by the conventional in-vitro experimental approach proposed to identify beneficial microbes by national and international guidelines. Afterward, LMG P-27481 was submitted to in-vitro assays targeted on diarrhea (lactose utilization, inhibition of pathogens such as bacteria and Rotavirus) revealing a stronger ability, compared to well-known reference strains, to antagonize Clostridium difficile (CD). Final confirmation of LMG P-27481 features in controlling CD colitis was achieved by an in-vivo trial on mice conditioned with large spectrum antibiotics before receiving CD challenge. Two out of the 3 antibiotic-treated groups received daily the probiotic strain LMG P-27481 with different duration in order to simulate a preventive approach (probiotic administered prior to CD challenge) or an antagonistic approach (probiotic administered after CD challenge). LMG P-27481 administration, with either protocols, significantly reduced CD DNA concentration in caecum and C. difficile toxins titer in the gut lumen, as compared to untreated controls. Moreover, LMG P-27481 supplementation significantly mitigated body weight loss, extent of inflammatory infiltrate and tissue damage. Despite the requirement for further in-vivo assessments on humans, the selection and characterization process targeted to diarrhea and CD infection, described in this study, identify the strain L. reuteri LMG P-27481 as a promising probiotic candidate in the course of CD infection.