Abstract
Background: In addition to strain taxonomy, the ability of probiotics to confer beneficial effects on the host rely on a number of additional factors including epigenetic modulation of bacterial genes leading to metabolic variability and might impact on probiotic functionality.Aims: To investigate metabolism and functionality of two different batches of a probiotic blend commercialized under the same name in Europe in models of intestinal inflammation.Methods: Boxes of VSL#3, a probiotic mixture used in the treatment of pouchitis, were obtained from pharmacies in UK subjected to metabolomic analysis and their functionality tested in mice rendered colitis by treatment with DSS or TNBS.Results: VSL#3-A (lot DM538), but not VSL#3-B (lot 507132), attenuated “clinical” signs of colitis in the DSS and TNBS models. In both models, VSL#3-A, but not VSL#3-B, reduced macroscopic scores, intestinal permeability, and expression of TNFα, IL-1β, and IL-6 mRNAs, while increased the expression of TGFβ and IL-10, occludin, and zonula occludens-1 (ZO-1) mRNAs and shifted colonic macrophages from a M1 to M2 phenotype (P < 0.05 vs. TNBS). In contrast, VSL#3-B failed to reduce inflammation, and worsened intestinal permeability in the DSS model (P < 0.001 vs. VSL#3-A). A metabolomic analysis of the two formulations allowed the identification of two specific patterns, with at least three-folds enrichment in the concentrations of four metabolites, including 1–3 dihydroxyacetone (DHA), an intermediate in the fructose metabolism, in VSL#3-B supernatants. Feeding mice with DHA, increased intestinal permeability.Conclusions: Two batches of a commercially available probiotic show divergent metabolic activities. DHA, a product of probiotic metabolism, increases intestinal permeability, highlighting the complex interactions between food, microbiota, probiotics, and intestinal inflammation.
Highlights
The World Health Organization’s defined probiotics in 2001 as “live microorganisms which, when administered in adequate amounts, confer a health benefit on the host.” A wide range of microbes and applications are included in this definition and, while it captures the essence of probiotics, it is widely accepted that probiotics for which non-strain-specific claims might be made could be restricted to Bifidobacterium and Lactobacillus
Because VSL#3 modulates the integrity of intestinal mucosal barrier, we have first investigated whether the two batches effectively reduce intestinal damage caused by feeding mice with DSS in drinking water
The histologic examination of colon sections stained with H&E demonstrated that treating DSS mice with VSL#3-A attenuated the severity of inflammation and leukocyte infiltration, while no improvement observed in mice administered VSL#3-B which increased the severity of colitis (Figures 1G,H)
Summary
The World Health Organization’s defined probiotics in 2001 as “live microorganisms which, when administered in adequate amounts, confer a health benefit on the host.” A wide range of microbes and applications are included in this definition and, while it captures the essence of probiotics, it is widely accepted that probiotics for which non-strain-specific claims might be made could be restricted to Bifidobacterium (adolescentis, animalis, bifidum, breve, and longum) and Lactobacillus (acidophilus, casei, fermentum, gasseri, johnsonii, paracasei, plantarum, rhamnosus, and salivarius). A wide range of microbes and applications are included in this definition and, while it captures the essence of probiotics, it is widely accepted that probiotics for which non-strain-specific claims might be made could be restricted to Bifidobacterium (adolescentis, animalis, bifidum, breve, and longum) and Lactobacillus (acidophilus, casei, fermentum, gasseri, johnsonii, paracasei, plantarum, rhamnosus, and salivarius). This list includes wellstudied species which could offer some benefits if taken daily at the dose of 1 billion colony forming units (1 × 109 CFU) viable cells. In addition to strain taxonomy, the ability of probiotics to confer beneficial effects on the host rely on a number of additional factors including epigenetic modulation of bacterial genes leading to metabolic variability and might impact on probiotic functionality
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