Oktober 2025 - Stefanie Widder

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Ap. Prof. Dr. Stefanie Widder

MedUni Wien RESEARCHER OF THE MONTH Oktober 2025

Chronic polymicrobial infection of the airways is a hallmark of obstructive lung diseases such as cystic fibrosis (CF), non-CF bronchiectasis, and chronic obstructive pulmonary disease. This persistent microbial imbalance, termed dysbiosis, drives pulmonary exacerbations, accelerates lung function decline and increases mortality, often resisting antimicrobial treatment. In the present study we characterized pulmonary dysbiosis patterns in people with CF and linked their (re)organization with disease dynamics and treatability. We gathered sputum samples in a prospective cohort study setting, sequenced pulmonary microbiota and analyzed their community networks. We identified two distinct paradigms of microbial organization – hierarchical and well-ordered versus flat and stochastic. The former dysbiosis type was governed by typical CF pathogens locating to top hierarchical positions, the latter type was driven by anaerobic organisms, while pathogens were less important for disease progression. Using patient-derived dysbiosis networks, we implemented a computational model to predict treatment efficacy for both dysbiosis types. The model predicted better therapy responses for hierarchically organized than for anaerobia dysbioses. This study offers new perspectives for tackling pulmonary infections and advancing personalized clinical management. The results suggest that antimicrobial interventions could be enhanced by tailoring therapy to microbiome architecture, ultimately improving outcomes for people with CF and, potentially, other obstructive lung diseases.

Selected Literature

1. Widder, S., Carmody, L.A., Opron, K., Kalikin, L.M., Caverly, L., LiPuma, J.J. Microbial community organization designates distinct pulmonary exacerbation types and predicts treatment outcome in cystic fibrosis. Nature Comms 15, 4889  (2024) doi: 10.1038/s41467-024-49150-y

2. World_Health_Organization. Global health estimates, www.who.int/data/global-health-estimates (2024)

3. Natalini, J., Singh, S. & Segal, L.N., The dynamic lung microbiome in health and disease. Nat Rev Microbiol 21: 222-235, (2023) doi:10.1038/s41579-022-00821-x.

4. Zhao, J., Schloss, P.D., Kalikin, L.M., Carmody, L., Foster, B., Petrosino, J., Cavalcoli J., VanDevanter D., Murray, S., Li, J., Young, V.B., LiPuma, J.J. Decade-long bacterial community dynamics in cystic fibrosis airways. Proc Natl Acad Sci U S A 109(15):5809-14 (2012). doi: 10.1073/pnas.1120577109

5. Rivett, D.W., Hatfield, L., Gavillet, H., Hardman, M., van der Gast, C. Bacterial interactions underpin worsening lung function in cystic fibrosis-associated infections. mBio 16(1):e0145624 (2025) doi: 10.1128/mbio.01456-24

6. Frey, D., Boutin, S., Dittrich, S.A., Graeber, S.Y., Stahl, M., Wege, S., Herth, F., Sommerburg, O., Schultz, C., Mall, M.A., Dalpke, A. Relationship between airway dysbiosis, inflammation and lung function in adults with cystic fibrosis. J Cyst Fibros 20(5):754-760, (2021). doi: 10.1016/j.jcf.2020.12.022.

7. Widder, S., Zhao, J., Carmody, L.A., Zhang, Q., Kalikin, L., Schloss, P.D., LiPuma, J.J. Association of bacterial community types, functional microbial processes and lung disease in cystic fibrosis airways. ISME J 2022 Apr;16(4):905-914. doi: 10.1038/s41396-021-01129-z

8. Pienkowska, K., Pust, M., Gessner. M., Gaedcke, S., Thavarasa, A., Rosenboom, I., Morán Losada, P., Minso, R., Arnold, C., Hedtfeld, S., Dorda, M., Wiehlmann, L., Mainz, J.G., Klockgether, J., Tümmler, B. The Cystic Fibrosis Upper and Lower Airway Metagenome. Microbiol Spectr 11(2):e0363322, (2023) doi: 10.1128/spectrum.03633-22.

9. [4] Agustí A., Bafadhel, M., Beasley, R., Bel, E., Faner, R., Gibson, P.G., Louis, R., McDonald, V.M., Sterk, P.J., Thomas, M., Vogelmeier, C., Pavord, I., on behalf of all participants in the seminar. Precision medicine in airway diseases: moving to clinical practice. Eur Respir J 50, (2017), doi:10.1183/13993003.01655-2017