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Respiratory Research
Published in: Respiratory Research 1/2014

Open Access 01-12-2014 | Research

Bifidobacterium breve and Lactobacillus rhamnosus treatment is as effective as budesonide at reducing inflammation in a murine model for chronic asthma

Published in: Respiratory Research | Issue 1/2014

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Abstract

Background

Asthma is estimated to affect as many as 300 million people worldwide and its incidence and prevalence are rapidly increasing throughout the world, especially in children and within developing countries. Recently, there has been a growing interest in the use of potentially beneficial bacteria for allergic diseases. This study is aimed at exploring the therapeutic effects of long-term treatment with two different beneficial bacterial strains (Bifidobacterium breve M-16 V and Lactobacillus rhamnosus NutRes1) and a glucocorticoid (budesonide), as a reference treatment, on inflammatory response in a murine model for chronic allergic asthma.

Methods

To mimic the chronic disease in asthmatic patients, we used the murine ovalbumin-induced asthma model combined with prolonged allergen exposure. Airway function; pulmonary airway inflammation; airway remodelling, mRNA expression of pattern recognition receptors, Th-specific cytokines and transcription factors in lung tissue; mast cell degranulation; in vitro T cell activation; and expression of Foxp3 in blood Th cells were examined.

Results

Lactobacillus rhamnosus reduced lung resistance to a similar extent as budesonide treatment in chronically asthmatic mice. Pulmonary airway inflammation, mast cell degranulation, T cell activation and airway remodelling were suppressed by all treatments. Beneficial bacteria and budesonide differentially modulated the expression of toll-like receptors (TLRs), nod-like receptors (NLRs), cytokines and T cell transcription factors. Bifidobacterium breve induced regulatory T cell responses in the airways by increasing Il10 and Foxp3 transcription in lung tissue as well as systemic by augmenting the mean fluorescence intensity of Foxp3 in blood CD4+ T cells.

Conclusion

These findings show that Bifidobacterium breve M-16 V and Lactobacillus rhamnosus NutRes1 have strong anti-inflammatory properties that are comparable to budesonide and therefore may be beneficial in the treatment of chronic asthma.
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Literature
1.
Navarro S, Cossalter G, Chiavaroli C, Kanda A, Fleury S, Lazzari A, Cazareth J, Sparwasser T, Dombrowicz D, Glaichenhaus N, Julia V: The oral administration of bacterial extracts prevents asthma via the recruitment of regulatory T cells to the airways. Mucosal Immunol. 2011, 4 (1): 53-65. 10.1038/mi.2010.51.PubMedCrossRef
2.
McMillan SJ, Lloyd CM: Prolonged allergen challenge in mice leads to persistent airway remodelling. Clin Exp Allergy. 2004, 34 (3): 497-507. 10.1111/j.1365-2222.2004.01895.x.PubMedPubMedCentralCrossRef
3.
Shifren A, Witt C, Christie C, Castro M: Mechanisms of remodeling in asthmatic airways. J Allergy (Cairo). 2012, 2012: 316049-Article ID 316049, 12 pages
4.
Cho JY: Recent advances in mechanisms and treatments of airway remodeling in asthma: message from the bench side to the clinic. Korean J Intern Med. 2011, 26 (4): 367-383. 10.3904/kjim.2011.26.4.367.PubMedPubMedCentralCrossRef
5.
Bai TR, Knight DA: Structural changes in the airways in asthma: observations and consequences. Clin Sci (Lond). 2005, 108 (6): 463-477. 10.1042/CS20040342.CrossRef
6.
Amin K, Janson C, Boman G, Venge P: The extracellular deposition of mast cell products is increased in hypertrophic airways smooth muscles in allergic asthma but not in nonallergic asthma. Allergy. 2005, 60 (10): 1241-1247. 10.1111/j.1398-9995.2005.00823.x.PubMedCrossRef
7.
Brightling CE, Bradding P, Symon FA, Holgate ST, Wardlaw AJ, Pavord ID: Mast-cell infiltration of airway smooth muscle in asthma. N Engl J Med. 2002, 346 (22): 1699-1705. 10.1056/NEJMoa012705.PubMedCrossRef
8.
Romagnani S: Coming back to a missing immune deviation as the main explanatory mechanism for the hygiene hypothesis. J Allergy Clin Immunol. 2007, 119 (6): 1511-1513. 10.1016/j.jaci.2007.04.005.PubMedCrossRef
9.
10.
Pejler G, Ronnberg E, Waern I, Wernersson S: Mast cell proteases: multifaceted regulators of inflammatory disease. Blood. 2010, 115 (24): 4981-4990. 10.1182/blood-2010-01-257287.PubMedCrossRef
11.
Sugimoto K, Kudo M, Sundaram A, Ren X, Huang K, Bernstein X, Wang Y, Raymond WW, Erle DJ, Abrink , Caughey GH, Huang X, Sheppard D: The alphavbeta6 integrin modulates airway hyperresponsiveness in mice by regulating intraepithelial mast cells. J Clin Invest. 2012, 122 (2): 748-758. 10.1172/JCI58815.PubMedPubMedCentralCrossRef
12.
Barnes PJ: Severe asthma: advances in current management and future therapy. J Allergy Clin Immunol. 2012, 129 (1): 48-59. 10.1016/j.jaci.2011.11.006.PubMedCrossRef
13.
Southam DS, Ellis R, Wattie J, Young S, Inman MD: Budesonide prevents but does not reverse sustained airway hyperresponsiveness in mice. Eur Respir J. 2008, 32 (4): 970-978. 10.1183/09031936.00125307.PubMedCrossRef
14.
Abe A, Ohtomo T, Koyama S, Kitamura N, Kaminuma O, Mori A: Comparative analysis of steroid sensitivity of T helper cells in vitro and in vivo. Int Arch Allergy Immunol. 2011, 155 (Suppl 1): 110-116.PubMedCrossRef
15.
Noverr MC, Huffnagle GB: Does the microbiota regulate immune responses outside the gut?. Trends Microbiol. 2004, 12 (12): 562-568. 10.1016/j.tim.2004.10.008.PubMedCrossRef
16.
Kranich J, Maslowski KM, Mackay CR: Commensal flora and the regulation of inflammatory and autoimmune responses. Semin Immunol. 2011, 23 (2): 139-145. 10.1016/j.smim.2011.01.011.PubMedCrossRef
17.
Georgiou NA, Garssen J, Witkamp RF: Pharma-nutrition interface: the gap is narrowing. Eur J Pharmacol. 2011, 651 (1-3): 1-8. 10.1016/j.ejphar.2010.11.007.PubMedCrossRef
18.
Vouloumanou EK, Makris GC, Karageorgopoulos DE, Falagas ME: Probiotics for the prevention of respiratory tract infections: a systematic review. Int J Antimicrob Agents. 2009, 34 (3): e191-e210.CrossRef
19.
Johannsen H, Prescott SL: Practical prebiotics, probiotics and synbiotics for allergists: how useful are they?. Clin Exp Allergy. 2009, 39 (12): 1801-1814. 10.1111/j.1365-2222.2009.03368.x.PubMedCrossRef
20.
Guarner F, Schaafsma GJ: Probiotics. Int J Food Microbiol. 1998, 39 (3): 237-238. 10.1016/S0168-1605(97)00136-0.PubMedCrossRef
21.
Gourbeyre P, Denery S, Bodinier M: Probiotics, prebiotics, and synbiotics: impact on the gut immune system and allergic reactions. J Leukoc Biol. 2011, 89 (5): 685-695. 10.1189/jlb.1109753.PubMedCrossRef
22.
Ezendam J, de Klerk A, Gremmer ER, van Loveren H: Effects of Bifidobacterium animalis administered during lactation on allergic and autoimmune responses in rodents. Clin Exp Immunol. 2008, 154 (3): 424-431. 10.1111/j.1365-2249.2008.03788.x.PubMedPubMedCentralCrossRef
23.
Hougee S, Vriesema AJ, Wijering SC, Knippels LM, Folkerts G, Nijkamp FP, Knol J, Garssen J: Oral treatment with probiotics reduces allergic symptoms in ovalbumin-sensitized mice: a bacterial strain comparative study. Int Arch Allergy Immunol. 2010, 151 (2): 107-117. 10.1159/000236000.PubMedCrossRef
24.
Forsythe P, Inman MD, Bienenstock J: Oral treatment with live Lactobacillus reuteri inhibits the allergic airway response in mice. Am J Respir Crit Care Med. 2007, 175 (6): 561-569. 10.1164/rccm.200606-821OC.PubMedCrossRef
25.
Eder W, Klimecki W, Yu L, von Mutius E, Riedler J, Braun-Fahrlander C, Nowak D, Holst O, Martinez FD: Association between exposure to farming, allergies and genetic variation in CARD4/NOD1. Allergy. 2006, 61 (9): 1117-1124. 10.1111/j.1398-9995.2006.01128.x.PubMedCrossRef
26.
Nonaka Y, Izumo T, Izumi F, Maekawa T, Shibata H, Nakano A, Kishi A, Akatani K, Kiso Y: Antiallergic effects of Lactobacillus pentosus strain S-PT84 mediated by modulation of Th1/Th2 immunobalance and induction of IL-10 production. Int Arch Allergy Immunol. 2008, 145 (3): 249-257. 10.1159/000109294.PubMedCrossRef
27.
Kalliomaki M, Antoine JM, Herz U, Rijkers GT, Wells JM, Mercenier A: Guidance for substantiating the evidence for beneficial effects of probiotics: prevention and management of allergic diseases by probiotics. J Nutr. 2010, 140 (3): 713S-721S. 10.3945/jn.109.113761.PubMedCrossRef
28.
Chen K, Xiang Y, Yao X, Liu Y, Gong W, Yoshimura T, Wang JM: The active contribution of Toll-like receptors to allergic airway inflammation. Int Immunopharmacol. 2011, 11 (10): 1391-1398. 10.1016/j.intimp.2011.05.003.PubMedCrossRef
29.
Uehara A, Fujimoto Y, Fukase K, Takada H: Various human epithelial cells express functional Toll-like receptors, NOD1 and NOD2 to produce anti-microbial peptides, but not proinflammatory cytokines. Mol Immunol. 2007, 44 (12): 3100-3111. 10.1016/j.molimm.2007.02.007.PubMedCrossRef
30.
Barnes PJ: The cytokine network in chronic obstructive pulmonary disease. Am J Respir Cell Mol Biol. 2009, 41 (6): 631-638. 10.1165/rcmb.2009-0220TR.PubMedCrossRef
31.
Boyce JA, Bochner B, Finkelman FD, Rothenberg ME: Advances in mechanisms of asthma, allergy, and immunology in 2011. J Allergy Clin Immunol. 2011, 129 (2): 335-341.CrossRef
32.
Heine H: TLRs, NLRs and RLRs: innate sensors and their impact on allergic diseases--a current view. Immunol Lett. 2011, 139 (1-2): 14-24. 10.1016/j.imlet.2011.04.010.PubMedCrossRef
33.
Eder W, Klimecki W, Yu L, von Mutius E, Riedler J, Braun-Fahrlander C, Nowak D, Martinez FD: Toll-like receptor 2 as a major gene for asthma in children of European farmers. J Allergy Clin Immunol. 2004, 113 (3): 482-488. 10.1016/j.jaci.2003.12.374.PubMedCrossRef
34.
Reijmerink NE, Bottema RW, Kerkhof M, Gerritsen J, Stelma FF, Thijs C, van Schayck CP, Smit HA, Brunekreef B, Koppelman GH, Postma DS: TLR-related pathway analysis: novel gene-gene interactions in the development of asthma and atopy. Allergy. 2010, 65 (2): 199-207. 10.1111/j.1398-9995.2009.02111.x.PubMedCrossRef
35.
Clarke TB, Davis KM, Lysenko ES, Zhou AY, Yu Y, Weiser JN: Recognition of peptidoglycan from the microbiota by Nod1 enhances systemic innate immunity. Nat Med. 2010, 16 (2): 228-231. 10.1038/nm.2087.PubMedPubMedCentralCrossRef
36.
Kabesch M, Peters W, Carr D, Leupold W, Weiland SK, von Mutius E: Association between polymorphisms in caspase recruitment domain containing protein 15 and allergy in two German populations. J Allergy Clin Immunol. 2003, 111 (4): 813-817. 10.1067/mai.2003.1336.PubMedCrossRef
37.
Reece P, Thanendran A, Crawford L, Tulic MK, Thabane L, Prescott SL, Sehmi R, Denburg JA: Maternal allergy modulates cord blood hematopoietic progenitor Toll-like receptor expression and function. J Allergy Clin Immunol. 2011, 127 (2): 447-453. 10.1016/j.jaci.2010.11.006.PubMedCrossRef
38.
Gupta GK, Agrawal DK: CpG oligodeoxynucleotides as TLR9 agonists: therapeutic application in allergy and asthma. BioDrugs. 2010, 24 (4): 225-235. 10.2165/11536140-000000000-00000.PubMedCrossRef
39.
Lachheb J, Dhifallah IB, Chelbi H, Hamzaoui K, Hamzaoui A: Toll-like receptors and CD14 genes polymorphisms and susceptibility to asthma in Tunisian children. Tissue Antigens. 2008, 71 (5): 417-425. 10.1111/j.1399-0039.2008.01011.x.PubMedCrossRef
40.
Stowell NC, Seideman J, Raymond HA, Smalley KA, Lamb RJ, Egenolf DD, Bugelski PJ, Murray LA, Marsters PA, Bunting RA, Flavell RA, Alexopoulou L, San Mateo LR, Griswold DE, Sarisky RT, Mbow ML, Das AM: Long-term activation of TLR3 by poly(I:C) induces inflammation and impairs lung function in mice. Respir Res. 2009, 10: 43-10.1186/1465-9921-10-43.PubMedPubMedCentralCrossRef
41.
Mizel SB, Honko AN, Moors MA, Smith PS, West AP: Induction of macrophage nitric oxide production by Gram-negative flagellin involves signaling via heteromeric Toll-like receptor 5/Toll-like receptor 4 complexes. J Immunol. 2003, 170 (12): 6217-6223. 10.4049/jimmunol.170.12.6217.PubMedCrossRef
42.
43.
Shi YH, Shi GC, Wan HY, Jiang LH, Ai XY, Zhu HX, Tang W, Ma JY, Jin XY, Zhang BY: Coexistence of Th1/Th2 and Th17/Treg imbalances in patients with allergic asthma. Chin Med J (Engl). 2011, 124 (13): 1951-1956.
44.
Robinson DS: The role of the T cell in asthma. J Allergy Clin Immunol. 2010, 126 (6): 1081-1091. 10.1016/j.jaci.2010.06.025. quiz 1092-1083PubMedCrossRef
45.
Provoost S, Maes T, van Durme YM, Gevaert P, Bachert C, Schmidt-Weber CB, Brusselle GG, Joos GF, Tournoy KG: Decreased FOXP3 protein expression in patients with asthma. Allergy. 2009, 64 (10): 1539-1546. 10.1111/j.1398-9995.2009.02056.x.PubMedCrossRef
46.
Vale-Pereira S, Todo-Bom A, Geraldes L, Schmidt-Weber C, Akdis CA, Mota-Pinto A: FoxP3, GATA-3 and T-bet expression in elderly asthma. Clin Exp Allergy. 2011, 41 (4): 490-496. 10.1111/j.1365-2222.2010.03640.x.PubMedCrossRef
47.
Braber S, Overbeek SA, Koelink PJ, Henricks PA, Zaman GJ, Garssen J, Kraneveld AD, Folkerts G: CXCR2 antagonists block the N-Ac-PGP-induced neutrophil influx in the airways of mice, but not the production of the chemokine CXCL1. Eur J Pharmacol. 2011, 668 (3): 443-449. 10.1016/j.ejphar.2011.03.025.PubMedCrossRef
48.
Fernandez-Rodriguez S, Ford WR, Broadley KJ, Kidd EJ: Establishing the phenotype in novel acute and chronic murine models of allergic asthma. Int Immunopharmacol. 2008, 8 (5): 756-763. 10.1016/j.intimp.2008.01.025.PubMedCrossRef
49.
50.
Janssen-Heininger YM, Irvin CG, Scheller EV, Brown AL, Kolls JK, Alcorn JF: Airway Hyperresponsiveness and Inflammation: causation, correlation, or no relation?. J Allergy Ther. 2012, 2012 (Suppl 1):
51.
Li CY, Lin HC, Hsueh KC, Wu SF, Fang SH: Oral administration of Lactobacillus salivarius inhibits the allergic airway response in mice. Can J Microbiol. 2010, 56 (5): 373-379. 10.1139/W10-024.PubMedCrossRef
52.
Yu J, Jang SO, Kim BJ, Song YH, Kwon JW, Kang MJ, Choi WA, Jung HD, Hong SJ: The effects of Lactobacillus rhamnosus on the prevention of asthma in a Murine model. Allergy Asthma Immunol Res. 2010, 2 (3): 199-205. 10.4168/aair.2010.2.3.199.PubMedPubMedCentralCrossRef
53.
Jang SO, Kim HJ, Kim YJ, Kang MJ, Kwon JW, Seo JH, Kim HY, Kim BJ, Yu J, Hong SJ: Asthma prevention by Lactobacillus Rhamnosus in a mouse model is associated with CD4(+)CD25(+)Foxp3(+) T Cells. Allergy Asthma Immunol Res. 2012, 4 (3): 150-156. 10.4168/aair.2012.4.3.150.PubMedPubMedCentralCrossRef
54.
Lun SW, Wong CK, Ko FW, Hui DS, Lam CW: Expression and functional analysis of toll-like receptors of peripheral blood cells in asthmatic patients: implication for immunopathological mechanism in asthma. J Clin Immunol. 2009, 29 (3): 330-342. 10.1007/s10875-008-9269-1.PubMedCrossRef
55.
Karagiannidis C, Akdis M, Holopainen P, Woolley NJ, Hense G, Ruckert B, Mantel PY, Menz G, Akdis CA, Blaser K, Schmidt-Weber CB: Glucocorticoids upregulate FOXP3 expression and regulatory T cells in asthma. J Allergy Clin Immunol. 2004, 114 (6): 1425-1433. 10.1016/j.jaci.2004.07.014.PubMedCrossRef
56.
Chauhan SK, Saban DR, Lee HK, Dana R: Levels of Foxp3 in regulatory T cells reflect their functional status in transplantation. J Immunol. 2009, 182 (1): 148-153. 10.4049/jimmunol.182.1.148.PubMedPubMedCentralCrossRef
57.
Sutmuller RP, den Brok MH, Kramer M, Bennink EJ, Toonen LW, Kullberg BJ, Joosten LA, Akira S, Netea MG, Adema GJ: Toll-like receptor 2 controls expansion and function of regulatory T cells. J Clin Invest. 2006, 116 (2): 485-494. 10.1172/JCI25439.PubMedPubMedCentralCrossRef
58.
Montuschi P, Barnes PJ: New perspectives in pharmacological treatment of mild persistent asthma. Drug Discov Today. 2011, 16 (23-24): 1084-1091. 10.1016/j.drudis.2011.09.005.PubMedCrossRef
59.
Kraneveld AD, van der Kleij HP, Kool M, van Houwelingen AH, Weitenberg AC, Redegeld FA, Nijkamp FP: Key role for mast cells in nonatopic asthma. J Immunol. 2002, 169 (4): 2044-2053. 10.4049/jimmunol.169.4.2044.PubMedCrossRef
60.
de Kivit S, Saeland E, Kraneveld AD, van de Kant HJ, Schouten B, van Esch BC, Knol J, Sprikkelman AB, van der Aa LB, Knippels LM, Garssen J, van Kooyk Y, Willemsen LE: Galectin-9 induced by dietary synbiotics is involved in suppression of allergic symptoms in mice and humans. Allergy. 2012, 67 (3): 343-352. 10.1111/j.1398-9995.2011.02771.x.PubMedCrossRef
61.
Park SK, Beaven MA: Mechanism of upregulation of the inhibitory regulator, src-like adaptor protein (SLAP), by glucocorticoids in mast cells. Mol Immunol. 2009, 46 (3): 492-497. 10.1016/j.molimm.2008.10.011.PubMedPubMedCentralCrossRef
62.
Kumar RK, Webb DC, Herbert C, Foster PS: Interferon-gamma as a possible target in chronic asthma. Inflamm Allergy Drug Targets. 2006, 5 (4): 253-256. 10.2174/187152806779010909.PubMedCrossRef
Metadata
Title
Bifidobacterium breve and Lactobacillus rhamnosus treatment is as effective as budesonide at reducing inflammation in a murine model for chronic asthma
Publication date
01-12-2014
Published in
Respiratory Research / Issue 1/2014
Electronic ISSN: 1465-993X
DOI
https://doi.org/10.1186/1465-9921-15-46

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