A Fixed Combination of Probiotics and Herbal Extracts Attenuates Intestinal Barrier Dysfunction from Inflammatory Stress in an In vitro Model Using Caco-2 Cells

Author(s): Veronica Cocetta, Daniela Catanzaro, Vittoria Borgonetti, Eugenio Ragazzi, Maria C. Giron, Paolo Governa, Ilaria Carnevali, Marco Biagi*, Monica Montopoli*.

Journal Name: Recent Patents on Food, Nutrition & Agriculture

Volume 10 , Issue 1 , 2019

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Abstract:

Background: Inflammatory Bowel Diseases (IBD), are considered a growing global disease, with about ten million people being affected worldwide. Maintenance of intestinal barrier integrity is crucial for preventing IBD onset and exacerbations. Some recent patents regarding oily formulations containing probiotics (WO2010122107A1 and WO2010103374A9) and the use of probiotics for gastrointestinal complaints (US20110110905A1 and US9057112B2) exist, or are pending application.

Objective: In this work, we studied the effect of a fixed combination of registered Lactobacillus reuteri and Lactobacillus acidophilus strains and herbal extracts in an in vitro inflammation experimental model.

Methods: Caco-2 cell monolayer was exposed to INF-γ+TNF-α or to LPS; Trans Epithelial Electrical Resistance (TEER) and paracellular permeability were investigated. ZO-1 and occludin Tight Junctions (TJs) were also investigated by mean of immunofluorescence.

Results: Pre-treatment with the fixed combination of probiotics and herbal extracts prevented the inflammation-induced TEER decrease, paracellular permeability increase and TJs translocation.

Conclusions: In summary, the fixed combination of probiotics and herbal extracts investigated in this research was found to be an interesting candidate for targeting the re-establishment of intestinal barrier function in IBD conditions.

Keywords: IBD, Caco-2 cells, Lactobacillus reuteri, Lactobacillus acidophilus, Trans Epithelial Electrical Resistance (TEER), adherence junctions proteins.

[1]
Catanzaro D, Rancan S, Orso G, Dall’Acqua S, Brun P, Giron MC, et al. Boswellia serrata preserves intestinal epithelial barrier from oxidative and inflammatory damage. PLoS One 2015; 10: e0125375.
[2]
Xavier RJ, Podolsky DK. Unravelling the pathogenesis of inflammatory bowel disease. Nature 2007; 448: 427-34.
[3]
Li P, Zheng Y, Chen X. Drugs for autoimmune inflammatory diseases: From small molecule compounds to anti-TNF biologics. Front Pharmacol 2017; 8: 460.
[4]
Guidi L, Pugliese D, Armuzzi A. Update on the management of inflammatory bowel disease: Specific role of adalimumab. Clin Exp Gastroenterol 2011; 4: 163-72.
[5]
Larussa T, Imeneo M, Luzza F. Potential role of nutraceutical compounds in inflammatory bowel disease. World J Gastroenterol 2017; 23: 2483-92.
[6]
Guo B-J, Bian Z-X, Qiu H-C, Wang Y-T, Wang Y. Biological and clinical implications of herbal medicine and natural products for the treatment of inflammatory bowel disease. Ann N Y Acad Sci 2017; 1401: 37-48.
[7]
Farzaei MH, Bahramsoltani R, Abdolghaffari AH, Sodagari HR, Esfahani SA, Rezaei N. A mechanistic review on plant-derived natural compounds as dietary supplements for prevention of inflammatory bowel disease. Expert Rev Gastroenterol Hepatol 2016; 10: 745-58.
[8]
Hummel S, Veltman K, Cichon C, Sonnenborn U, Schmidt MA. Differential targeting of the E-Cadherin/beta-Catenin complex by gram-positive probiotic lactobacilli improves epithelial barrier function. Appl Environ Microbiol 2012; 78: 1140-7.
[9]
Korada SK, Yarla NS, Bishayee A, Aliev G, Aruna Lakshmi K, Arunasree MK, et al. Can probiotics cure inflammatory bowel diseases? Curr Pharm Des 2016; 22: 904-17.
[10]
Ghouri YA, Richards DM, Rahimi EF, Krill JT, Jelinek KA, DuPont AW. Systematic review of randomized controlled trials of probiotics, prebiotics, and symbiotics in inflammatory bowel disease. Clin Exp Gastroenterol 2014; 7: 473-87.
[11]
Laval L, Martin R, Natividad JN, Chain F, Miquel S, Desclee de Maredsous C, et al. Lactobacillus rhamnosus CNCM I-3690 and the commensal bacterium Faecalibacterium prausnitzii A2-165 exhibit similar protective effects to induced barrier hyper-permeability in mice. Gut Microbes 2015; 6: 1-9.
[12]
Lightfoot YL, Selle K, Yang T, Goh YJ, Sahay B, Zadeh M, et al. SIGNR3-dependent immune regulation by Lactobacillus acidophilus surface layer protein A in colitis. EMBO J 2015; 34: 881-95.
[13]
Kirejevas V, Kazarjan A. Probiotic oil suspension and use thereof. WO2010122107A1 2010.
[14]
Strozzi GP, Mogna L. Oily suspension containing probiotic bacteria for paediatric uses. WO2010103374A9 2012.
[15]
Ritchie JA. Infant Colic Supplement. US20110110905A1 2011.
[16]
Connolly E, Mollstam B. Use of selected lactic acid bacteria for reducing infantile colic. US9057112B2 2015.
[17]
Morini E. Package for keeping products separate before use. US6148996A 2000.
[18]
Wang F, Vallen GW, Wang Y, Witkowski ED, Schwarz BT, Turner JR. Interferon-γ and tumor necrosis factor-α synergize to induce intestinal epithelial barrier dysfunction by up-regulating myosin light chain kinase expression. Am J Pathol 2005; 166: 409-19.
[19]
Srinivasan B, Kolli AR, Esch MB, Abaci HE, Shuler ML, Hickman JJ. TEER measurement techniques for in vitro barrier model systems. J Lab Autom 2015; 20: 107-26.
[20]
Leonard M, Creed E, Brayden D, Baird AW. Evaluation of the Caco-2 monolayer as a model epithelium for iontophoretic transport. Pharm Res 2000; 17: 1181-8.
[21]
Kowapradit J, Opanasopit P, Ngawhirunpat T, Apirakaramwong A, Rojanarata T, Ruktanonchai U, et al. In vitro Permeability enhancement in intestinal epithelial cells (caco-2) monolayer of water soluble quaternary ammonium chitosan derivatives. AAPS PharmSciTech 2010; 11: 497-508.
[22]
Suzuki T. Regulation of intestinal epithelial permeability by tight junctions. Cell Mol Life Sci 2013; 70: 631-59.
[23]
Peterson MD, Mooseker MS. An in vitro model for the analysis of intestinal brush border assembly. I. Ultrastructural analysis of cell contact-induced brush border assembly in Caco-2BBe cells. J Cell Sci 1993; 105(Pt 2): 445-60.
[24]
Fleet JC, Wang L, Vitek O, Craig BA, Edenberg HJ. Gene expression profiling of Caco-2 BBe cells suggests a role for specific signaling pathways during intestinal differentiation. Physiol Genomics 2003; 13: 57-68.
[25]
Mariadason JM, Arango D, Corner GA, Arañes MJ, Hotchkiss KA, Yang W, et al. A gene expression profile that defines colon cell maturation in vitro. Cancer Res 2002; 62: 4791-804.
[26]
Zhu H, Li YR. Oxidative stress and redox signaling mechanisms of inflammatory bowel disease: Updated experimental and clinical evidence. Exp Biol Med 2012; 237: 474-80.
[27]
Pavlick KP, Laroux FS, Fuseler J, Wolf RE, Gray L, Hoffman J, et al. Role of reactive metabolites of oxygen and nitrogen in inflammatory bowel disease. Free Radic Biol Med 2002; 33: 311-22.
[28]
Wang F, Schwarz BT, Graham WV, Wang Y, Su L, Clayburgh DR, et al. IFN-gamma-induced TNFR2 expression is required for TNF-dependent intestinal epithelial barrier dysfunction. Gastroenterology 2006; 131: 1153-63.
[29]
Hering NA, Fromm M, Schulzke J-D. Determinants of colonic barrier function in inflammatory bowel disease and potential therapeutics. J Physiol 2012; 590: 1035-44.
[30]
Jiang Y, Lü X, Man C, Han L, Shan Y, Qu X, et al. Lactobacillus acidophilus induces cytokine and chemokine production via NF-κB and p38 mitogen-activated protein kinase signaling pathways in intestinal epithelial cells. Clin Vaccine Immunol 2012; 19: 603-8.
[31]
Da-Yong R, Chang L, Yan-Qing Q, Rong-Lan Y, Shou-Wen D, Fei Y, et al. Lactobacilli reduce chemokine IL-8 production in response to TNF-α and Salmonella challenge of Caco-2 cells. BioMed Res Int 2013; 2013: Article ID: 925219.
[32]
Santangelo C, Vari R, Scazzocchio B, De Sanctis P, Giovannini C, D’Archivio M, et al. Anti-inflammatory activity of extra virgin olive oil polyphenols: Which role in the prevention and treatment of immune-mediated inflammatory diseases? Endocr Metab Immune Disord Drug Targets 2018; 18: 36-50.
[33]
Incani A, Serra G, Atzeri A, Melis MP, Serreli G, Bandino G, et al. Extra virgin olive oil phenolic extracts counteract the pro-oxidant effect of dietary oxidized lipids in human intestinal cells. Food Chem Toxicol 2016; 90: 171-80.
[34]
Rodriguez-Ramiro I, Martin MA, Ramos S, Bravo L, Goya L. Olive oil hydroxytyrosol reduces toxicity evoked by acrylamide in human Caco-2 cells by preventing oxidative stress. Toxicology 2011; 288: 43-8.
[35]
Muto E, Dell’Agli M, Sangiovanni E, Mitro N, Fumagalli M, Crestani M, et al. Olive oil phenolic extract regulates interleukin-8 expression by transcriptional and posttranscriptional mechanisms in Caco-2 cells. Mol Nutr Food Res 2015; 59: 1217-21.
[36]
Manna C, Galletti P, Cucciolla V, Moltedo O, Leone A, Zappia V. The protective effect of the olive oil polyphenol (3,4-Dihydroxyphenyl)- ethanol counteracts reactive oxygen metabolite–induced cytotoxicity in Caco-2 Cells. J Nutr 1997; 127: 286-92.
[37]
Sánchez-Fidalgo S, Sánchez de Ibargüen L, Cárdeno A, Alarcón de la Lastra C. Influence of extra virgin olive oil diet enriched with hydroxytyrosol in a chronic DSS colitis model. Eur J Nutr 2012; 51: 497-506.
[38]
Minaiyan M. ghassemi-Dehkordi N, Mahzouni P, Ansari-Roknabady M. Effect of Matricaria aurea (Loefl.) Shultz-Bip. hydroalcoholic extract on acetic acid-induced acute colitis in rats. Iran J Basic Med Sci 2011; 14: 67-74.
[39]
World Health Organization, WHO Monographs on Selected Medicinal PlantsVolume 1 World Health Organization:. Geneva, Switzerland 1999
[40]
Ortiz MI, Carino-Cortes R, Ponce-Monter HA, Gonzalez-Garcia MP, Castaneda-Hernandez G, Salinas-Caballero M. Synergistic Interaction of Matricaria Chamomilla extract with diclofenac and indomethacin on carrageenan-induced paw inflammation in rats. Drug Dev Res 2017; 78: 360-7.
[41]
Turner JR. Intestinal mucosal barrier function in health and disease. Nat Rev Immunol 2009; 9: 799-809.
[42]
Shin K, Fogg VC, Margolis B. Tight junctions and cell polarity. Annu Rev Cell Dev Biol 2006; 22: 207-35.
[43]
Harhaj NS, Antonetti DA. Regulation of tight junctions and loss of barrier function in pathophysiology. Int J Biochem Cell Biol 2004; 36: 1206-37.
[44]
Liu H, Wang P, Cao M, Li M, Wang F. Protective role of oligomycin against intestinal epithelial barrier dysfunction caused by IFN-γ and TNF-a. Cell Physiol Biochem 2012; 29: 799-808.
[45]
Li Q, Zhang Q, Wang M, Zhao S, Ma J, Luo N, et al. Interferon-gamma and tumor necrosis factor-alpha disrupt epithelial barrier function by altering lipid composition in membrane microdomains of tight junction. Clin Immunol 2008; 126: 67-80.
[46]
John LJ, Fromm M, Schulzke J-D. Epithelial barriers in intestinal inflammation. Antioxid Redox Signal 2011; 15: 1255-70.
[47]
Lee SH. Intestinal permeability regulation by tight junction: implication on inflammatory bowel diseases. Intest Res 2015; 13: 11-8.


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Article Details

VOLUME: 10
ISSUE: 1
Year: 2019
Page: [62 - 69]
Pages: 8
DOI: 10.2174/2212798410666180808121328

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