Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2014 Apr 16;15(1):46.
doi: 10.1186/1465-9921-15-46.

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

Affiliations

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

Seil Sagar et al. Respir Res. .

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.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Time schedule of the chronic asthma mouse model. Male BALB/c mice were sensitised intraperitoneally to OVA-ImjectAlum on days 0 and 12 and mice were challenged from day 17 until day 23 daily with aerosolised OVA or saline. From day 22 until day 55, mice were treated 3 times a week with either PBS or budesonide by oropharyngeal aspiration or beneficial bacteria (B. breve or L. rhamnosus) by oral gavage. 1 h after treatment, from day 24 until day 55, mice were challenged 3 times/week with aerosolised OVA or saline. Mice were sacrificed on day 56 after pulmonary function measurement.
Figure 2
Figure 2
Beneficial bacteria and budesonide reduce the differential BAL fluid cell counts in chronic asthmatic mice. Pulmonary inflammation is represented by the influx of macrophages (M), lymphocytes (L), eosinophils (E) and neutrophils (N) in the BAL fluid. Differential cell counts are shown as percentages of the total cell count for each group. The charts show the mean, n = 6 mice/group. Statistical significance of differences was tested using post hoc Bonferroni’s multiple comparison test after one-way ANOVA. #Statistically significant difference (p < 0.05) compared to OVA/Sal-PBS mice. ¤Statistically significant difference (p < 0.05) compared to OVA/OVA-PBS mice. Statistically significant difference (p < 0.05) compared to the OVA/Sal group in each treatment group. BUD = budesonide.
Figure 3
Figure 3
Beneficial bacteria modulate TLR and NLR mRNA expression in lung tissue of chronically asthmatic mice. Data is shown as mean ± SEM, n = 6 mice/group, of the TLR and NLR mRNA expression levels in OVA-sensitised, Sal-challenged (OVA/Sal; white bars) mice and OVA-sensitised, OVA-challenged (OVA/OVA; black bars) mice treated with PBS (A), B. breve(B), budesonide (C) or L. rhamnosus(D). The results are presented as mRNA expression levels relative to levels found in the OVA/Sal-PBS mice (white bars in figure A). Statistical significance of differences was tested using the post hoc Bonferroni’s multiple comparison test after one-way ANOVA. #Statistically significant difference (p < 0.05) compared to the OVA/Sal-PBS group. ¤Statistically significant difference (p < 0.05) compared to the OVA/OVA-PBS group. Statistically significant difference (p < 0.05) compared to the OVA/Sal group in each treatment group.
Figure 4
Figure 4
Beneficial bacteria and budesonide modulate cytokine mRNA expression in lung tissue of chronically asthmatic mice. Data is shown as mean ± SEM, n = 6 mice/group, of the cytokine mRNA expression levels in OVA-sensitised, Sal-challenged (OVA/Sal; white bars) mice and OVA-sensitised, OVA-challenged (OVA/OVA; black bars) mice treated with PBS (A), B. breve(B), budesonide (C) or L. rhamnosus(D). The results are presented as mRNA expression levels relative to levels found in the OVA/Sal-PBS mice (white bars in figure A). Statistical significance of differences was tested using the post hoc Bonferroni’s multiple comparison test after one-way ANOVA. #Statistically significant difference (p < 0.05) compared to the OVA/Sal-PBS group. ¤Statistically significant difference (p < 0.05) compared to the OVA/OVA-PBS group. Statistically significant difference (p < 0.05) compared to the OVA/Sal group in each treatment group.
Figure 5
Figure 5
B. breve treatment up-regulates Tbet and Foxp3 mRNA expression in lungs of chronically asthmatic mice. Data is shown as mean ± SEM, n = 6 mice/group, of the transcription factor mRNA expression levels in OVA-sensitised, Sal-challenged (OVA/Sal) mice and OVA-sensitised, OVA-challenged (OVA/OVA) mice treated with PBS (A), B. breve(B), budesonide (C) or L. rhamnosus(D). The results are presented as mRNA expression levels relative to levels found in the OVA/Sal-PBS mice (white bars in figure A). Statistical significance of differences was tested using the post hoc Bonferroni’s multiple comparison test after one-way ANOVA. #Statistically significant difference (p < 0.05) compared to the OVA/Sal-PBS group. ¤Statistically significant difference (p < 0.05) compared to the OVA/OVA-PBS group. Statistically significant difference (p < 0.05) compared to the OVA/Sal group in each treatment group.
Figure 6
Figure 6
Beneficial bacteria and budesonide increase Foxp3 expression in blood Treg cells of chronically asthmatic mice. T cells were isolated on day 56 from mouse whole blood from OVA-sensitised, Sal-challenged (OVA/Sal) mice and OVA-sensitised, OVA-challenged (OVA/OVA) mice for each treatment. (A) Percentage of CD4 cells that are Foxp3+. (B) Percentage of CD4 cells that are Foxp3+ and CD25hi. (C) Real mean fluorescence intensity (MFI) of Foxp3 in Treg cells. (D) MFI levels relative to the OVA/Sal-PBS group (white bar). Data is shown as mean ± SEM, n = 6 mice/group. Statistical significance of differences was tested using the post hoc Bonferroni’s multiple comparison test after one-way ANOVA. #Statistically significant difference (p < 0.05) compared to the OVA/Sal-PBS group. ¤Statistically significant difference (p < 0.05) compared to the OVA/OVA-PBS group. BUD = budesonide.
Figure 7
Figure 7
Beneficial bacteria and budesonide reduce mouse mast cell protease-1 levels in serum of chronic asthmatic mice. Mouse serum was isolated on day 56 and mouse mast cell protease-1 (mMCP-1) levels were measured by ELISA. Data is shown as mean ± SEM, n = 5-6mice/group. #Statistically significant difference (p < 0.05) compared to the OVA/Sal-PBS group. ¤Statistically significant difference (p < 0.05) compared to the OVA/OVA-PBS group. BUD = budesonide.
Figure 8
Figure 8
Beneficial bacteria and budesonide suppress cytokine production by T cells in TLNs of chronic asthmatic mice. Thoracic lymph nodes (TLNs) were isolated from mice on day 56 and restimulated in vitro with plate-bound anti-CD3 monoclonal antibody or medium only for 5 days (37°C, 5% CO2). Data is shown as mean of cytokine concentration (ng/ml) ± SEM, n = 6 mice/group. Statistical significance of differences was tested using post hoc Bonferroni’s multiple comparison test after one-way ANOVA. #Statistically significant difference (p < 0.05) compared to the OVA/Sal-PBS group. ¤Statistically significant difference (p < 0.05) compared to the OVA/OVA-PBS group.
Figure 9
Figure 9
Beneficial bacteria and budesonide suppress airway remodelling features in chronic asthmatic mice. Representative photomicrographs for 5 mice/group of hitstological and immunohistochemical staining for inflammation (hematoxylin-eosin, HE); goblet cells (periodic acid Schiff, PAS); connective tissue (Masson trichrome, Masson); Anti-α-smooth muscle actin (α-smooth muscle) and proliferating cells (Anti-Ki67) in lung tissue of sensitised only (OVA/Sal) and sensitised and challenged (OVA/OVA) mice treated with PBS, B. breve, L. rhamnosus or budesonide (BUD). Original magnification, 40X, except for anti-Ki67 100X.

Similar articles

Cited by

References

    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. doi: 10.1038/mi.2010.51. - DOI - PubMed
    1. McMillan SJ, Lloyd CM. Prolonged allergen challenge in mice leads to persistent airway remodelling. Clin Exp Allergy. 2004;34(3):497–507. doi: 10.1111/j.1365-2222.2004.01895.x. - DOI - PMC - PubMed
    1. 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. - PMC - PubMed
    1. 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. doi: 10.3904/kjim.2011.26.4.367. - DOI - PMC - PubMed
    1. Bai TR, Knight DA. Structural changes in the airways in asthma: observations and consequences. Clin Sci (Lond) 2005;108(6):463–477. doi: 10.1042/CS20040342. - DOI - PubMed