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.
Highlights
A variety of studies have evaluated the efficacy of probiotics in treating diarrhea, which represents a potentially serious health problem with more than 4 billion cases reported world-wide every year. McFarland et al (2018) carried out an extensive systematic meta-analysis of the results of randomized controlled trials examining the use of probiotics to treat different types of diseases.Fighting Gut Pathogens With L. reuteriIn accordance with Ouwehand (2017), the investigators confirmed the strain- and disease-specificity of probiotics in treating diarrhea
The LMG P-27481 strain was selected from other human isolates belonging to the Lactobacillus reuteri species in view of its susceptibility to antibiotics according to the breakpoint values
As described by Etzold et al (2014) and Bath et al (2005), our experiments showed that the strain carried five sequences with a significant homology to mucus-binding proteins, cell wall anchor domains, and signal peptides characterizing the surfaceexposed adhesins from L. reuteri
Summary
A variety of studies have evaluated the efficacy of probiotics in treating diarrhea, which represents a potentially serious health problem with more than 4 billion cases reported world-wide every year. McFarland et al (2018) carried out an extensive systematic meta-analysis of the results of randomized controlled trials examining the use of probiotics to treat different types of diseases.Fighting Gut Pathogens With L. reuteriIn accordance with Ouwehand (2017), the investigators confirmed the strain- and disease-specificity of probiotics in treating diarrhea. Despite a wide heterogeneity across clinical studies, some probiotics have been found to be effective in treating antibiotic-associated adult diarrhea, Clostridium difficile diarrhea (CDAD), acute Rotavirus diarrhea, radiation therapy-related diarrhea, and enteral nutrition-related diarrhea. Their efficacy in treating traveler’s diarrhea (TD) has not, been supported by clinical data (Williams and Adcock, 2018). Hypothetical mechanisms explaining probiotics’ effects include competitive inhibition of pathogens, stabilization of the resident microbiota, and attenuation of increased gut barrier permeability. Their beneficial effects in terms of reducing the duration and intensity of fever has been demonstrated in children they did not seem to affect the number of daily evacuations and accompanying symptoms such as vomiting (Salari et al, 2012)
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