The Epithelial Barrier Model Shows That the Properties of VSL#3 Depend from Where it is Manufactured

Abstract

Background: VSL#3 has been extensively investigated and is currently recommended for the prevention and treatment of chronic pouchitis and ulcerative colitis. Nonetheless, in vitro and in vivo studies have recently shown variability in the VSL#3 efficacy often attributed to the manufacturing process. Objective: The aim was to comparatively study the in vitro effects of two VSL#3 preparations produced in different sites (named US- and Italy-made VSL#3) on CaCo-2 epithelial barrier model in terms of trans-epithelial electrical resistance (TEER), dextran flux and expression of Tight Junctions (TJ) proteins i.e. zonulin-1 (ZO-1) and occludin, in the absence or presence of a heat stress-related damage of monolayer. Methods: TEER was evaluated on CaCo-2 differentiated monolayers. Epithelial permeability of polarized monolayers was assessed by measuring the FITC-labeled dextran flux from the apical to basolateral chambers. ZO-1/occludin levels were analyzed by western blot analysis. A set of experiments was performed to compare the effects of both VSL#3 on TEER values, dextran flux and ZO-1/occludin expression in CaCo-2 monolayers after heat stress exposure. Results: US- and Italy-made VSL#3 have opposing effects on TEER values, dextran flux, and ZO- 1/occludin expression, being all these parameters negatively influenced just by Italy-made product. US-made probiotic did not affect baseline TEER, dextran flux and ZO-1 expression and strongly increased occludin levels. Of note, pre-treatment of monolayer with US-made VSL#3, but not Italy-made product, totally prevented the heat-induced epithelial barrier integrity loss. Conclusion: Our data trigger the need for reassessing efficacy or safety of the Italy-made VSL#3 considering intestinal epithelial barrier plays an important role in maintaining host health.

The Effects of Low-Nickel Diet Combined with Oral Administration of Selected Probiotics on Patients with Systemic Nickel Allergy Syndrome (SNAS) and Gut Dysbiosis

“…The specific mechanisms of action underlying the benefits of a probiotic treatment other than the normalization of perturbed intestinal microbiota communities also include direct effects on intestinal epithelial mucosa and modulation of the immune system [46][47][48]. Of interest, through in vitro models the direct beneficial effects of selected probiotics on damaged intestinal epithelial barrier have been recently reported by our group [49,50]. In this context, it may be useful to investigate the effect of appropriate probiotic administration on intestinal barrier function other than the dysbiosis level in SNAS patients.…”

Soluble Fraction from Lysates of Selected Probiotic Strains Differently Influences Re-Epithelialization of HaCaT Scratched Monolayer Through a Mechanism Involving Nitric Oxide Synthase 2

“…Finally, in the light of a number of recent scientific reports [55][56][57][58][59][60][61], changes in the manufacturing processes, equipment, or facilities, which could result in detrimental differences in the final probiotic product, should be strictly controlled in terms of safety and efficacy.…”

A Combined Proteomics, Metabolomics and In Vivo Analysis Approach for the Characterization of Probiotics in Large-Scale Production

“…Grześkowiak studied several L. rhamnosus GG isolates from different probiotic products and confirmed that some beneficial properties were lost depending on the manufacturing site, notwithstanding the genetic identity of the strains tested [3]. Recently, some publications also discussed the equivalence of the VSL#3 probiotic formulation produced in two different manufacturing facilities [4][5][6].…”

“…Despite that VSL#3 strains were reported with different names in the two products and the relative concentrations of the eight strains components were not given, Italian and American products were commercialized under the same brand and the producer did not declare any difference in composition between them. Hence, as in previous works [4][5][6], we considered the two products as having identical formulation.…”