Login Register Cart 0
Generic placeholder image

Endocrine, Metabolic & Immune Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

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

Author(s): Paola Palumbo*, Francesca Lombardi, Maria Grazia Cifone and Benedetta Cinque

Volume 19, Issue 2, 2019

Page: [199 - 206] Pages: 8

DOI: 10.2174/1871530318666181022164505

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.

Keywords: VSL#3, probiotics, epithelial barrier, heat stress, trans-epithelial electrical resistance, dextran flux, zonulin-1, occludin.

« Previous Next »
Graphical Abstract

[1]
Sashihara, T.; Sueki, N.; Furuichi, K.; Ikegami, S. Effect of growth conditions of Lactobacillus gasseri OLL2809 on the immunostimulatory activity for production of interleukin-12 (p70) by murine splenocytes. Int. J. Food Microbiol., 2007, 120(3), 274-281.
[2]
van Baarlen, P.; Troost, F.J.; van Hemert, S.; van der Meer, C.; de Vos, W.M.; de Groot, P.J.; Hooiveld, G.J.; Brummer, R.J.; Kleerebezem, M. Differential NF-kappaB pathways induction by Lactobacillus plantarum in the duodenum of healthy humans correlating with immune tolerance. Proc. Natl. Acad. Sci. USA, 2009, 106(7), 2371-2376.
[3]
Jankovic, I.; Sybesma, W.; Phothirath, P.; Ananta, E.; Mercenier, A. Application of probiotics in food products-challenges and new approaches. Curr. Opin. Biotechnol., 2010, 21(2), 175-181.
[4]
Sanders, M.E.; Klaenhammer, T.R.; Ouwehand, A.C.; Pot, B.; Johansen, E.; Heimbach, J.T.; Marco, M.L.; Tennilä, J.; Ross, R.P.; Franz, C.; Pagé, N.; Pridmore, R.D.; Leyer, G.; Salminen, S.; Charbonneau, D.; Call, E.; Lenoir-Wijnkoop, I. Effects of genetic, processing, or product formulation changes on efficacy and safety of probiotics. Ann. N. Y. Acad. Sci., 2014, 1309, 1-18.
[5]
Zacarías, M.F.; Souza, T.C.; Zaburlín, N. Influence of technological treatments on the functionality of bifidobacterium lactis INL1, a breast milk-derived probiotic. J. Food Sci., 2017, 82(10), 2462-2470.
[6]
Toshimitsu, T.; Ozaki, S.; Mochizuki, J.; Furuichi, K.; Asami, Y. Effects of Lactobacillus plantarum strain OLL2712 culture conditions on the anti-inflammatory activities for murine immune cells and obese and type 2 diabetic mice. Appl. Environ. Microbiol., 2017, 83(7), e03001-e03016.
[7]
Gionchetti, P.; Rizzello, F.; Venturi, A.; Brigidi, P.; Matteuzzi, D.; Bazzocchi, G.; Poggioli, G.; Miglioli, M.; Campieri, M. Oral bacteriotherapy as maintenance treatment in patients with chronic pouchitis: a double-blind, placebo-controlled trial. Gastroenterology, 2000, 119(2), 305-309.
[8]
Gionchetti, P.; Rizzello, F.; Helwig, U.; Venturi, A.; Lammers, K.M.; Brigidi, P.; Vitali, B.; Poggioli, G.; Miglioli, M.; Campieri, M. Prophylaxis of pouchitis onset with probiotic therapy: A double-blind, placebo-controlled trial. Gastroenterology, 2003, 124(5), 1202-1209.
[9]
Shen, J.; Zuo, Z.X.; Mao, A.P. Effect of probiotics on inducing remission and maintaining therapy in ulcerative colitis, Crohn’s disease, and pouchitis: Meta-analysis of randomized controlled trials. Inflamm. Bowel Dis., 2014, 20(1), 21-35.
[10]
Cinque, B.; La Torre, C.; Lombardi, F.; Palumbo, P.; Van der Rest, M.; Cifone, M.G. Production conditions affect the in vitro anti-tumoral effects of a high concentration multi-strain probiotic preparation. PLoS One, 2016, 11(9), e0163216.
[11]
Cinque, B.; La Torre, C.; Lombardi, F.; Palumbo, P.; Evtoski, Z.; Jr Santini, S.; Falone, S.; Cimini, A.; Amicarelli, F.; Cifone, M.G. VSL#3 probiotic differently influences IEC-6 intestinal epithelial cell status and function. J. Cell. Physiol., 2017, 232(12), 3530-3539.
[12]
Biagioli, M.; Laghi, L.; Carino, A.; Cipriani, S.; Distrutti, E.; Marchianò, S.; Parolin, C.; Scarpelli, P.; Vitali, B.; Fiorucci, S. Metabolic variability of a multispecies probiotic preparation impacts on the anti-inflammatory activity. Front. Pharmacol., 2017, 8, 505.
[13]
Trinchieri, V.; Laghi, L.; Vitali, B. Efficacy and safety of a multistrain probiotic formulation depends from manufacturing. Front. Immunol., 2017, 8, 1474.
[14]
Sambuy, Y.; De Angelis, I.; Ranaldi, G.; Scarino, M.L.; Stammati, A.; Zucco, F. The Caco-2 cell line as a model of the intestinal barrier: Influence of cell and culture-related factors on Caco-2 cell functional characteristics. Cell Biol. Toxicol., 2005, 21(1), 1-26.
[15]
Varasteh, S.; Fink-Gremmels, J.; Garssen, J.; Braber, S. α-Lipoic acid prevents the intestinal epithelial monolayer damage under heat stress conditions: Model experiments in Caco-2 cells. Eur. J. Nutr., 2018, 57(4), 1577-1589.
[16]
Zhang, J.; Lu, Y.; Wei, J.; Li, L.; Han, L. Protective effect of carboxytmethylpachymaran on TNF-α-induced damage in Caco-2 cell monolayers. Int. J. Biol. Macromol., 2016, 93(Pt A), 506-511,
[17]
Anderson, R.C.; Cookson, A.L.; McNabb, W.C.; Kelly, W.J.; Roy, N.C. Lactobacillus plantarum DSM 2648 is a potential probiotic that enhances intestinal barrier function. FEMS Microbiol. Lett., 2010, 309(2), 184-192.
[18]
Morini, J.; Babini, G.; Barbieri, S.; Baiocco, G.; Ottolenghi, A. The interplay between radioresistant Caco-2 cells and the immune system increases epithelial layer permeability and alters signaling protein spectrum. Front. Immunol., 2017, 8, 223.
[19]
Primavera, R.; Palumbo, P.; Celia, C.; Cinque, B.; Carata, E.; Carafa, M.; Paolino, D.; Cifone, M.G.; Di Marzio, L. An insight of in vitro transport of PEGylated non-ionic surfactant vesicles (NSVs) across the intestinal polarized enterocyte monolayers. Eur. J. Pharm. Biopharm., 2018, 127, 432-442.
[20]
Xiao, G.; Tang, L.; Yuan, F. Eicosapentaenoic acid enhances heat stress-impaired intestinal epithelial barrier function in Caco-2 cells. PLoS One, 2013, 8(9), e73571.
[21]
Grześkowiak, Ł.; Isolauri, E.; Salminen, S.; Gueimonde, M. Manufacturing process influences properties of probiotic bacteria. Br. J. Nutr., 2010, 105, 887-894.
[22]
Clements, M.L.; Levine, M.M.; Ristaino, P.A.; Daya, V.E.; Hughes, T.P. Exogenous lactobacilli fed to man – their fate and ability to prevent diarrheal disease. Prog. Food Nutr. Sci., 1983, 7, 29-37.
[23]
Lipinska, L.; Klewicki, R.; Elżbieta, K.; Kolodziejczyk, K.; Sójka, M.; Nowak, A. Antifungal activity of Lactobacillus sp. bacteria in the presence of xylitol and galactosyl-xylitol. BioMed Res. Int., 2016, 1-8.
[24]
Otte, J.M.; Podolsky, D.K. Functional modulation of enterocytes by grampositive and gram-negative microorganisms. Am. J. Physiol. Gastrointest. Liver Physiol., 2004, 286(4), G613-G626.
[25]
Dai, C.; Zhao, D.H.; Jiang, M. VSL#3 probiotics regulate the intestinal epithelial barrier in vivo and in vitro via the p38 and ERK signaling pathways. Int. J. Mol. Med., 2012, 29(2), 202-208.
[26]
Krishnan, M.; Penrose, H.M.; Shah, N.N.; Marchelletta, R.R.; McCole, D.F. VSL#3 probiotic stimulates T-cell protein tyrosine phosphatase–mediated recovery of IFN-γ–induced intestinal epithelial barrier defects. Inflamm. Bowel Dis., 2016, 22(12), 2811-2823.
[27]
Shibolet, O.; Karmeli, F.; Eliakim, R.; Swennen, E.; Brigidi, P.; Gionchetti, P.; Campieri, M.; Morgenstern, S.; Rachmilewitz, D. Variable response to probiotics in two models of experimental colitis in rats. Inflamm. Bowel Dis., 2002, 8(6), 399-406.
[28]
Di Giacinto, C.; Marinaro, M.; Sanchez, M.; Strober, W.; Boirivant, M. Probiotics ameliorate recurrent Th1-mediated murine colitis by inducing IL-10 and IL-10-dependent TGF-beta-bearing regulatory cells. J. Immunol., 2005, 174(6), 3237-3246.
[29]
Mennigen, R.; Nolte, K.; Rijcken, E.; Utech, M.; Loeffler, B.; Senninger, N.; Bruewer, M. Probiotic mixture VSL#3 protects the epithelial barrier by maintaining tight junction protein expression and preventing apoptosis in a murine model of colitis. Am. J. Physiol. Gastrointest. Liver Physiol., 2009, 296(5), G1140-G1149.
[30]
Kumar, M.; Kissoon-Singh, V.; Coria, A.L.; Moreau, F.; Chadee, K. Probiotic mixture VSL#3 reduces colonic inflammation and improves intestinal barrier function in Muc2 mucin-deficient mice. Am. J. Physiol. Gastrointest. Liver Physiol., 2017, 312(1), G34-G45.
[31]
Chelakkot, C.; Ghim, J.; Ryu, S.H. Mechanisms regulating intestinal barrier integrity and its pathological implications. Exp. Mol. Med., 2018, 50(8), 103.
[32]
Allain, T.; Amat, C.B.; Motta, J.P.; Manko, A.; Buret, A.G. Interactions of Giardia sp. with the intestinal barrier: Epithelium, mucus, and microbiota. Tissue Barriers, 2017, 5(1), e1274354.
[33]
Halpern, M.D.; Denning, P.W. The role of intestinal epithelial barrier function in the development of NEC. Tissue Barriers, 2015, 3(1-2), e1000707.
[34]
Moore, S.A.; Nighot, P.; Reyes, C.; Rawat, M.; McKee, J.; Lemon, D.; Hanson, J.; Ma, T.Y. Intestinal barrier dysfunction in human necrotizing enterocolitis. J. Pediatr. Surg., 2016, 51(12), 1907-1913.
[35]
Douillard, F.P.; Mora, D.; Eijlander, R.T.; Wels, M.; de Vos, W.M. Comparative genomic analysis of the multispecies probiotic-marketed product VSL#3. PLoS One, 2018, 13(2), e0192452.
[36]
Kolaček, S.; Hojsak, I.; Berni Canani, R.; Guarino, A.; Indrio, F.; Orel, R.; Pot, B.; Shamir, R.; Szajewska, H.; Vandenplas, Y.; van Goudoever, J.; Weizman, Z. ESPGHAN working group for probiotics and prebiotics. Commercial probiotic products: A call for improved quality control. A Position Paper by the ESPGHAN working group for probiotics and prebiotics. J. Pediatr. Gastroenterol. Nutr., 2017, 65(1), 117-124.

Rights & Permissions Print Cite
Article Metrics
63
6
© 2024 Bentham Science Publishers | Privacy Policy