The online version of this article (doi:10.1186/1465-9921-15-46) contains supplementary material, which is available to authorized users.
Seil Sagar, Mary E Morgan, Si Chen, Johan Garssen, Gert Folkerts and Aletta D Kraneveld are employees of the Utrecht University and declare that they do not have a conflict of interest. Arjan P Vos, Jeroen van Bergenhenegouwen and Niki A Georgiou are employed by Danone Research as indicated in the author affiliations. This aside, there are no personal or financial conflicts of interest to report. Louis Boon is employed by Bioceros B.V. and has no personal financial conflicts of interest to report.
SS, designed and ran the chronic asthma mouse model, performed all in vivo and in vitro experiments, collected and analysed data, and wrote the manuscript. MEM, supervised the flow cytometry analysis and advised on data analysis. SC, carried out real-time-PCR analysis, and interpreted and analysed the data. APV and JB provided beneficial bacteria and gave technical support and conceptual advice. ADK, GF, NAG and JG, gave advice on model design, supervised the study and advised on data analysis. LB provided the anti-CD3 antibody. All authors discussed the results and implications and commented on the manuscript at all stages. All authors read and approved the final manuscript.
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.
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.
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.
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.
Additional file 2: Figure S1: Representative dot plots of T cells analysis in the blood. T cells were isolated on day 56 from whole blood of OVA-sensitised, Sal-challenged (OVA/Sal) mice and OVA-sensitised, OVA-challenged (OVA/OVA) mice treated with PBS (I), B. breve (II), L. rhamnosus (III) or budesonide (IV; BUD). T cells were gated based on FSC-SSC pattern, followed by analysis of expression of CD4. Then co-expression of Foxp3 and CD25 (regulatory T cells; Treg) was analyzed. Data is representative for n = 6 mice/group. (PDF 75 KB)
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- Bifidobacterium breve and Lactobacillus rhamnosus treatment is as effective as budesonide at reducing inflammation in a murine model for chronic asthma
Mary E Morgan
Arjan P Vos
Jeroen van Bergenhenegouwen
Niki A Georgiou
Aletta D Kraneveld
- BioMed Central
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