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Exacerbation of allergic rhinitis by the commensal bacterium Streptococcus salivarius

Nature Microbiology volume 8, pages 218–230 (2023)Cite this article

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Abstract

Allergic rhinitis (AR)—commonly called hay fever—is a widespread condition that affects the quality of life of millions of people. The pathophysiology of AR remains incompletely understood. In particular, it is unclear whether members of the colonizing nasal microbiota contribute to AR. Here, using 16S ribosomal RNA sequencing, we show that the nasal microbiome of patients with AR (n = 55) shows distinct differences compared with that from healthy individuals (n = 105), including decreased heterogeneity and the increased abundance of one species, Streptococcus salivarius. Using ex vivo and in vivo models of AR, we demonstrate that this commensal bacterium contributes to AR development, promoting inflammatory cytokine release and morphological changes in the nasal epithelium that are characteristic of AR. Our data indicate that this is due to the ability of S. salivarius to adhere to the nasal epithelium under AR conditions. Our study indicates the potential of targeted antibacterial approaches for AR therapy.

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Fig. 1: Nasal microbiome composition in patients with AR.
Fig. 2: S. salivarius exacerbates pathophysiology of AR in a mouse model.
Fig. 3: S. salivarius promotes cytokine gene expression in allergen-induced epithelial cells.
Fig. 4: S. salivarius shows strong adhesion to nasal epithelia under allergen-induced conditions.

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Data availability

Raw microbiome sequencing data (related to data shown in Fig. 1, Table 1 and Extended Data Figs. 1–6) and genome sequencing data have been deposited in NCBI’s Sequencing Read Archive (SRA) database under Bioproject numbers PRJNA796497 and PRJNA874865, respectively. All other data are presented in this paper. Bacterial strains are available from M.L. Source data are provided with this paper.

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Acknowledgements

This work was supported by the Clinical Research Plan of the Shanghai Shenkang Hospital Development Center (SHDC, grant number SHDC2020CR3006A to M.L.), the National Natural Science Foundation of China (grant numbers 81873957 and 82172325, to M.L.) and the Intramural Research Program of Allergy and Infectious Diseases (NIAID), US National Institutes of Health (NIH) (project number ZIA AI000904, to M.O.).

Author information

Author notes

  1. Yue Zheng

    Present address: Innovent Biologics (USA), Rockville, MD, USA

  2. These authors contributed equally: Ping Miao, Yiming Jiang, Ying Jian.

Authors and Affiliations

  1. Department of Laboratory Medicine, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

    Ping Miao, Ying Jian, Yao Liu, Qian Liu & Min Li

  2. Pathogen Molecular Genetics Section, Laboratory of Bacteriology, National Institute of Allergy and Infectious Diseases, US National Institutes of Health, Bethesda, MD, USA

    Ping Miao, Pipat Piewngam, Yue Zheng, Gordon Y. C. Cheung & Michael Otto

  3. Departments of Otorhinolaryngology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

    Yiming Jiang & Jiali Shi

  4. Faculty of Medical Laboratory Science, College of Health Science and Technology, Shanghai Jiao Tong University School of Medicine, Shanghai, China

    Min Li

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Contributions

Conceptualization, M.O. and M.L. Methodology, P.M. and M.L. Investigation, P.M., Y. Jiang, J.S., Y.L., P.P., Y.Z., G.Y.C.C., Y. Jian and Q.L. Funding acquisition, M.L. and M.O. Supervision, M.L. and M.O. Writing, M.O.

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Correspondence to Michael Otto or Min Li.

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Nature Microbiology thanks Cathryn Nagler and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Extended data

Extended Data Fig. 1 Analysis of group composition.

a, Relative species abundance and evenness by rank abundance (Whittaker) plots. b, Total OTU in HR and AC groups. Statistical analysis is by two-tailed Mann-Whitney test. Error bars show the mean ± SD. n = 55 (AR), n = 102 (HC).

Extended Data Fig. 2 Relative abundance in single individuals of main detected phyla in AR patients versus HC.

Statistical analysis is by two-tailed Mann-Whitney tests. Error bars show the mean ± SD. n = 55 (AR), n = 102 (HC).

Extended Data Fig. 3 Analysis of absolute bacterial abundance.

a, Bacterial CFU obtained from nasal swabs from n = 18 individuals/group, grown in aerobic and anaerobic conditions. Error bars show the mean ± SD. Statistical analysis is by two-tailed Mann-Whitney tests. All comparisons were not significant (p≥0.05). b, Absolute abundance according to 16S rRNA sequencing analysis.

Source data

Extended Data Fig. 4 Relative abundance in single individuals of main detected genera in AR patients versus HC.

Statistical analysis is by two-tailed Mann-Whitney tests. Error bars show the mean ± SD. n = 55 (AR), n = 102 (HC).

Extended Data Fig. 5 Microbiome analysis by type of AR (severity, seasonality, frequency).

a, α-diversity (Shannon indices). Statistical analysis is by Mann-Whitney tests. Error bars show the mean ± SD. b, β-diversity (PCoA analyses). Statistical analysis is by Adonis. c, Relative abundances on the phylum level. d, Relative abundances on the genus level. a-d, n = 55 (all AR).

Extended Data Fig. 6 Microbiome analysis by sex and age of participants.

a, α-diversity (Shannon indices). Statistical analysis is by two-tailed Mann-Whitney tests. Error bars show the mean ± SD. b, β-diversity (PCoA analyses). Statistical analysis is by Adonis. c, Relative abundances on the phylum level. d, Relative abundances on the genus level. a-d, n = 55 (all AR).

Extended Data Fig. 7 Absolute abundance of Staphylococcus and S. epidermidis in AR patients versus HC.

a, Absolute abundance by OTUs. b, Abundance by qPCR. n = 52 (AR), n = 58 (HR) (all samples with sufficient DNA for qRT-PCR analysis). a,b, Statistical analysis is by two-tailed Mann-Whitney tests. Error bars show the mean ± SD.

Source data

Extended Data Fig. 8 Agar diffusion test of antibacterial activity of S. salivarius nasal isolates obtained from AR patients.

All obtained 14 nasal isolates from AR patients were spotted on agar plates with embedded M. luteus, S. epidermidis, C. acnes, or C. accolens. Asterisks designate strains with detected bacteriocin genes in the genome. Vancomycin (Van) and supernatant obtained from the micrococcin MP1 producer S. hominis S34-1 were used as positive controls.

Extended Data Fig. 9 Repeat of experiment shown in Fig. 2 of the main manuscript.

a, Cytokine expression data. b, Epithelial thickness. n = 10. See legend to Fig. 2 for further details. Statistical analysis is by 1-way ANOVAs with Tukey’s post-tests. Error bars show the mean ± SD.

Source data

Extended Data Table 1 Cytokines in the blood of AR patients
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Miao, P., Jiang, Y., Jian, Y. et al. Exacerbation of allergic rhinitis by the commensal bacterium Streptococcus salivarius. Nat Microbiol 8, 218–230 (2023). https://doi.org/10.1038/s41564-022-01301-x

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