The Biotherapeutic Potential of Lactobacillus reuteri Characterized Using a Target-Specific Selection Process

Valeria Sagheddu; Francesca Uggeri; Luisella Belogi; Laura Remollino; Paola Brun; Giulia Bernabè; Giancarlo Moretti; Andrea Porzionato; Lorenzo Morelli; Ignazio Castagliuolo; Marina Elli

doi:10.3389/fmicb.2020.00532

The Biotherapeutic Potential of Lactobacillus reuteri Characterized Using a Target-Specific Selection Process

Front Microbiol. 2020 Apr 15:11:532. doi: 10.3389/fmicb.2020.00532. eCollection 2020.

Authors

Affiliations

¹ AAT-Advanced Analytical Technologies S.r.l., Fiorenzuola d'Arda, Italy.
² Moviscom S.r.l., Rome, Italy.
³ Nòos S.r.l., Rome, Italy.
⁴ Department of Molecular Medicine, University of Padua, Padua, Italy.
⁵ Department of Neurosciences, University of Padua, Padua, Italy.
⁶ Department for Sustainable Food Process - DiSTAS, Università Cattolica del Sacro Cuore, Piacenza, Italy.

Abstract

A growing body of clinical and experimental data supports the view that the efficacy of probiotics is strain-specific and restricted to particular pathological conditions, which means that newly isolated probiotic strains need to be targeted to a specific disease. Following national and international guidelines, we used a conventional in vitro experimental approach to characterize a novel strain of Lactobacillus reuteri, LMG P-27481, for safety (sensitivity to antibiotics and genome analysis) and putative efficacy (resistance to gastro-intestinal transit, adhesiveness, induction of cytokines, and release of antimicrobial metabolites). In vitro assays, which were carried out to examine the probiotic's effect on diarrhea (lactose utilization, inhibition of pathogens such as bacteria and Rotavirus), showed that it was more efficacious with respect to well-known reference strains in antagonizing Clostridioides difficile (CD). Data confirming that the probiotic can effectively treat CD colitis was gained from in vivo trials involving mice conditioned with large spectrum antibiotics before they were subjected to CD challenge. Two out of the three antibiotic-treated groups received daily LMG P-27481 for different time durations in order to simulate a preventive approach (LMG P-27481 administered prior to CD challenge) or an antagonistic one (LMG P-27481 administered after CD challenge). Both approaches significantly reduced, with respect to the untreated controls, CD DNA concentrations in caecum and C. difficile toxin titers in the gut lumen. In addition, LMG P-27481 supplementation significantly mitigated body weight loss and the extent of inflammatory infiltrate and tissue damage. The study results, which need to be confirmed by in vivo clinical trials, have demonstrated that the L. reuteri LMG P-27481 strain is a promising probiotic candidate for the treatment of CD infection.

Keywords: diarrhea; gut; intestine; lactobacilli; pathogen; probiotic.