Early nasal microbiota and subsequent respiratory tract infections in infants with cystic fibrosis

Ruth Steinberg; Nadja Mostacci; Elisabeth Kieninger; Bettina Frauchiger; Carmen Casaulta; Jakob Usemann; Alexander Moeller; Daniel Trachsel; Isabelle Rochat; Sylvain Blanchon; Dominik Mueller-Suter; Barbara Kern; Maura Zanolari; Urs Frey; Kathryn A Ramsey; Markus Hilty; Philipp Latzin; Insa Korten; SCILD study group; BILD study group

doi:10.1038/s43856-024-00616-6

Early nasal microbiota and subsequent respiratory tract infections in infants with cystic fibrosis

Commun Med (Lond). 2024 Nov 23;4(1):246. doi: 10.1038/s43856-024-00616-6.

Authors

Ruth Steinberg^{1

2

3}, Nadja Mostacci⁴, Elisabeth Kieninger¹, Bettina Frauchiger¹, Carmen Casaulta¹, Jakob Usemann^{3

5}, Alexander Moeller⁵, Daniel Trachsel³, Isabelle Rochat⁶, Sylvain Blanchon⁶, Dominik Mueller-Suter⁷, Barbara Kern⁷, Maura Zanolari⁸, Urs Frey³, Kathryn A Ramsey^{1

9}, Markus Hilty⁴, Philipp Latzin¹, Insa Korten¹⁰; SCILD study group; BILD study group

Affiliations

¹ Division of Paediatric Respiratory Medicine and Allergology, Departement of Paediatrics, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
² Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland.
³ Paediatric Intensive Care and Pulmonology, University Children's Hospital Basel (UKBB), Basel, Switzerland.
⁴ Institute for Infectious Diseases, University of Bern, Bern, Switzerland.
⁵ Department of Respiratory Medicine and Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland.
⁶ Pediatric Pulmonology and Cystic Fibrosis Unit, Division of Pediatrics, Department of Woman-Mother-Child, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
⁷ Division of Pediatric Pneumology, Kantonsspital Aarau, Aarau, Switzerland.
⁸ Division of Pediatrics, Hospital Bellinzona, Bellinzona, Switzerland.
⁹ Wal-yan Respiratory Research Centre, Telethon Kids Institute, University of Western Australia, Perth, WA, Australia.
¹⁰ Division of Paediatric Respiratory Medicine and Allergology, Departement of Paediatrics, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. insa.korten@insel.ch.

Abstract

Background: Respiratory tract infections (RTIs) drive lung function decline in children with cystic fibrosis (CF). While the respiratory microbiota is clearly associated with RTI pathogenesis in infants without CF, data on infants with CF is scarce. We compared nasal microbiota development between infants with CF and controls and assessed associations between early-life nasal microbiota, RTIs, and antibiotic treatment in infants with CF.

Methods: We included 50 infants with CF and 30 controls from two prospective birth cohorts followed throughout the first year of life. We collected 1511 biweekly nasal swabs and analyzed the microbiota after amplifying the V3-V4 region of the 16S rRNA gene. We conducted structured weekly interviews to assess respiratory symptoms and antibiotic treatment. We calculated generalized additive mixed models and permutational analysis of variance.

Results: Here, we show that the nasal microbiota is already altered before the first RTI or antibiotic treatment in infants with CF. Microbiota diversity differs between infants with CF and controls following RTIs and/or antibiotic treatment. CF infants with lower α-diversity have a higher number of subsequent RTIs.

Conclusions: Early nasal microbiota alterations may reflect predisposition or predispose to RTIs in infants with CF, and further change after RTIs and antibiotic treatment. This highlights the potential of targeting the nasal microbiota in CF-related RTI management, while also questioning current practices in the era of novel modulator therapies.

Plain language summary

Cystic fibrosis (CF) is an inherited condition which can increase the risk of developing respiratory tract infections (RTIs). We investigated the microorganisms present in the respiratory tract of infants from birth to the age of one. We found that infants with CF had differences in the microorganisms present immediately after birth compared to infants without CF. These differences increased after development of RTIs and following antibiotic treatment. Our results suggest that infants with CF could potentially benefit from treatments that modify microorganisms present in their respiratory tract prior to development of any RTI, or from different antibiotics to those used by infants without CF.