House dust exposure mediates gut microbiome Lactobacillus enrichment and airway immune defense against allergens and virus infection - PubMed (original) (raw)
House dust exposure mediates gut microbiome Lactobacillus enrichment and airway immune defense against allergens and virus infection
Kei E Fujimura et al. Proc Natl Acad Sci U S A. 2014.
Abstract
Exposure to dogs in early infancy has been shown to reduce the risk of childhood allergic disease development, and dog ownership is associated with a distinct house dust microbial exposure. Here, we demonstrate, using murine models, that exposure of mice to dog-associated house dust protects against ovalbumin or cockroach allergen-mediated airway pathology. Protected animals exhibited significant reduction in the total number of airway T cells, down-regulation of Th2-related airway responses, as well as mucin secretion. Following dog-associated dust exposure, the cecal microbiome of protected animals was extensively restructured with significant enrichment of, amongst others, Lactobacillus johnsonii. Supplementation of wild-type animals with L. johnsonii protected them against both airway allergen challenge or infection with respiratory syncytial virus. L. johnsonii-mediated protection was associated with significant reductions in the total number and proportion of activated CD11c(+)/CD11b(+) and CD11c(+)/CD8(+) cells, as well as significantly reduced airway Th2 cytokine expression. Our results reveal that exposure to dog-associated household dust results in protection against airway allergen challenge and a distinct gastrointestinal microbiome composition. Moreover, the study identifies L. johnsonii as a pivotal species within the gastrointestinal tract capable of influencing adaptive immunity at remote mucosal surfaces in a manner that is protective against a variety of respiratory insults.
Keywords: Lactobacilliaceae; airway adaptive immunity; gastrointestinal bacterial community; house environment.
Conflict of interest statement
The authors declare no conflict of interest.
Figures
Fig. 1.
Exposure of animals to dust from homes with dogs attenuates the development of allergen-induced airways disease and serum IgE. (A) Whole-lung mRNA analysis by Q-PCR demonstrates a significant decrease in IL-4 and IL-13 in D dust-supplemented, but not in NP-supplemented animals compared with controls. (B) Accompanying the Th2 cytokine reduction was significantly reduced expression of the mucus-associated gene, gob5. (C) Reduced airway mucus secretion and goblet cell metaplasia is observed in the D dust-supplemented animals, as depicted by PAS staining in lung histology. (D) A reduction in draining lymph node numbers in D dust-supplemented animals was also observed. (E) Serum IgE levels reflected the reduction in the development of the Th2 environment in the D dust-supplemented animals. Data represent the mean ± SE from five mice per group; *P < 0.05.
Fig. 2.
(A) Exposure to house dust alters cecal microbiome composition. UniFrac-based cluster analysis of cecal microbiota of control, D dust- and NP dust-supplemented animals reveals distinct microbiota compositions in each treatment group. (B) Phylogenetic tree displaying all taxa that exhibited significant (P < 0.05; q < 0.15) relative enrichment (red bars) or depletion (green bars) in airway-protected mice supplemented with D-associated house dust compared with unprotected control animals. Phyla are indicted by color: Acidobacteria (light blue), Actinobacteria (teal), Bacteriodetes (purple), Firmicutes (green), Proteobacteria (red), and other (orange). Family designation of highly enriched or depleted taxa are indicated.
Fig. 3.
Supplementation of mice with L. johnsonii attenuates the development of allergic airways disease. (A) Examination of allergen-induced airway hyperactivity (AHR) following methacholine (250 μg/kg, i.v.) exposure demonstrated reduced responses in _L. johnsonii_-supplemented animals. (B) Th2 cytokine mRNA in the lungs (black bars) and protein expression in allergen-restimulated lymph node cells (gray bars) indicated a significant attenuation in _L. johnsonii_-supplemented mice. (C) Upon CRA exposure (black bars), significant increases in total leukocytes, granulocytes (neutrophils and eosinophils), and (D) in total and inflammatory (Ly6c+) DC populations were only observed in the control but not the _L. johnsonii_-supplemented animals (CRA-unexposed controls represented by white bars). (E) Histologic staining with PAS stain revealed a distinct reduction in the inflammatory and mucogenic responses in _L. johnsonii_-supplemented animals. Data represent mean ± SE from five mice per group. *P < 0.05, **P < 0.01.
Fig. 4.
Viable L. johnsonii is necessary to attenuate RSV-induced airway responses. (A) Viable (vLj) but not heat-killed (hkLj) L. johnsonii supplementation protects animals from RSV-induced airway hyperreactivity (AHR) assessed at 8 d postinfection. (B) Histologic examination of lungs from RSV-infected animals demonstrates reduced inflammation and PAS-stained airway mucus only in the treatment group who received viable organisms. (C) RSV-restimulated lymph node cell-induced cytokine responses are significantly lower in animals who received viable L. johnsonii supplements. (D) Significant reductions in the number of various leukocyte subsets in the lungs are only observed in animals who received viable L. johnsonii. Data represent mean ± SE from five mice per group. *P < 0.05.
Fig. 5.
(A) _L. johnsonii_-supplemented animals that exhibit airway protection exhibit altered cecal microbiome composition. Nonmetric dimensional scaling based on a UniFrac distance matrix reveals that microbial communities of mice supplemented with L. johnsonii are compositionally and phylogenetically distinct from unsupplemented animals. Ellipses constructed around each treatment group indicate the 95% confidence intervals. (B) Compared with unsupplemented control animals, communities supplemented with L. johnsonii or L. johnsonii followed by CRA exposure exhibit the greatest phylogenetic distance (*P < 0.0005, **P < 0.0001, respectively).
Similar articles
- Lactobacillus johnsonii supplementation attenuates respiratory viral infection via metabolic reprogramming and immune cell modulation.
Fonseca W, Lucey K, Jang S, Fujimura KE, Rasky A, Ting HA, Petersen J, Johnson CC, Boushey HA, Zoratti E, Ownby DR, Levine AM, Bobbit KR, Lynch SV, Lukacs NW. Fonseca W, et al. Mucosal Immunol. 2017 Nov;10(6):1569-1580. doi: 10.1038/mi.2017.13. Epub 2017 Mar 15. Mucosal Immunol. 2017. PMID: 28295020 Free PMC article. - Airway house dust extract exposures modify allergen-induced airway hypersensitivity responses by TLR4-dependent and independent pathways.
Lam D, Ng N, Lee S, Batzer G, Horner AA. Lam D, et al. J Immunol. 2008 Aug 15;181(4):2925-32. doi: 10.4049/jimmunol.181.4.2925. J Immunol. 2008. PMID: 18684984 Free PMC article. - Maternal gut microbiome regulates immunity to RSV infection in offspring.
Fonseca W, Malinczak CA, Fujimura K, Li D, McCauley K, Li J, Best SKK, Zhu D, Rasky AJ, Johnson CC, Bermick J, Zoratti EM, Ownby D, Lynch SV, Lukacs NW, Ptaschinski C. Fonseca W, et al. J Exp Med. 2021 Nov 1;218(11):e20210235. doi: 10.1084/jem.20210235. Epub 2021 Oct 6. J Exp Med. 2021. PMID: 34613328 Free PMC article. - Modeling responses to respiratory house dust mite exposure.
Cates EC, Fattouh R, Johnson JR, Llop-Guevara A, Jordana M. Cates EC, et al. Contrib Microbiol. 2007;14:42-67. doi: 10.1159/000107054. Contrib Microbiol. 2007. PMID: 17684332 Review. - Influence and effect of the human microbiome in allergy and asthma.
Panzer AR, Lynch SV. Panzer AR, et al. Curr Opin Rheumatol. 2015 Jul;27(4):373-80. doi: 10.1097/BOR.0000000000000191. Curr Opin Rheumatol. 2015. PMID: 26002029 Review.
Cited by
- Gut microbiota dysbiosis and its impact on asthma and other lung diseases: potential therapeutic approaches.
Kim YC, Sohn KH, Kang HR. Kim YC, et al. Korean J Intern Med. 2024 Sep;39(5):746-758. doi: 10.3904/kjim.2023.451. Epub 2024 Aug 30. Korean J Intern Med. 2024. PMID: 39252487 Free PMC article. Review. - Link between gut microbiota dysbiosis and childhood asthma: Insights from a systematic review.
Aslam R, Herrles L, Aoun R, Pioskowik A, Pietrzyk A. Aslam R, et al. J Allergy Clin Immunol Glob. 2024 Jun 12;3(3):100289. doi: 10.1016/j.jacig.2024.100289. eCollection 2024 Aug. J Allergy Clin Immunol Glob. 2024. PMID: 39105129 Free PMC article. Review. - Environmental and structural factors associated with bacterial diversity in household dust across the Arizona-Sonora border.
Benton LD, Lopez-Galvez N, Herman C, Caporaso JG, Cope EK, Rosales C, Gameros M, Lothrop N, Martínez FD, Wright AL, Carr TF, Beamer PI. Benton LD, et al. Sci Rep. 2024 Jun 4;14(1):12803. doi: 10.1038/s41598-024-63356-6. Sci Rep. 2024. PMID: 38834753 Free PMC article. - The gut-airway microbiome axis in health and respiratory diseases.
Özçam M, Lynch SV. Özçam M, et al. Nat Rev Microbiol. 2024 Aug;22(8):492-506. doi: 10.1038/s41579-024-01048-8. Epub 2024 May 22. Nat Rev Microbiol. 2024. PMID: 38778224 Review. - Microbiome Dynamics: A Paradigm Shift in Combatting Infectious Diseases.
Kamel M, Aleya S, Alsubih M, Aleya L. Kamel M, et al. J Pers Med. 2024 Feb 18;14(2):217. doi: 10.3390/jpm14020217. J Pers Med. 2024. PMID: 38392650 Free PMC article. Review.
References
- Nistal E, et al. Differences in faecal bacteria populations and faecal bacteria metabolism in healthy adults and celiac disease patients. Biochimie. 2012;94(8):1724–1729. - PubMed
- Tremaroli V, Bäckhed F. Functional interactions between the gut microbiota and host metabolism. Nature. 2012;489(7415):242–249. - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Research Materials