Early-life viral infections are associated with disadvantageous immune and microbiota profiles and recurrent respiratory infections

• Published in: Nature microbiology Vol. 7; no. 2; pp. 224 - 237
• Main Authors: de Steenhuijsen Piters, Wouter A. A., Watson, Rebecca L., de Koff, Emma M., Hasrat, Raiza, Arp, Kayleigh, Chu, Mei Ling J. N., de Groot, Pieter C. M., van Houten, Marlies A., Sanders, Elisabeth A. M., Bogaert, Debby
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.02.2022; Nature Publishing Group
• Subjects: 38; 38/61; 38/90; 45/77; 631/250/254; 631/326/2565/2134; 64; 692/420/254; Biomedical and Life Sciences; Birth; Cohort Studies; Female; Gene expression; Gene Expression Profiling; Haemophilus - immunology; Host Microbial Interactions; Humans; Infant; Infant, Newborn; Infants; Infections; Infectious Diseases; Inflammasomes; Interferon; Life Sciences; Male; Medical Microbiology; Microbiology; Microbiota; Microbiota - genetics; Microbiota - immunology; Moraxella - immunology; Nasopharynx - virology; Parasitology; Recurrence; Respiratory tract diseases; Respiratory tract infection; Respiratory Tract Infections - immunology; Respiratory Tract Infections - physiopathology; Respiratory Tract Infections - virology; Species Specificity; Toll-like receptors; Viral infections; Virology; Virus Diseases - immunology
• ISSN: 2058-5276; 2058-5276
• DOI: 10.1038/s41564-021-01043-2

The respiratory tract is populated by a specialized microbial ecosystem, which is seeded during and directly following birth. Perturbed development of the respiratory microbial community in early-life has been associated with higher susceptibility to respiratory tract infections (RTIs). Given a consistent gap in time between first signs of aberrant microbial maturation and the observation of the first RTIs, we hypothesized that early-life host–microbe cross-talk plays a role in this process. We therefore investigated viral presence, gene expression profiles and nasopharyngeal microbiota from birth until 12 months of age in 114 healthy infants. We show that the strongest dynamics in gene expression profiles occurred within the first days of life, mostly involving Toll-like receptor (TLR) and inflammasome signalling. These gene expression dynamics coincided with rapid microbial niche differentiation. Early asymptomatic viral infection co-occurred with stronger interferon activity, which was related to specific microbiota dynamics following, including early enrichment of Moraxella and Haemophilus spp. These microbial trajectories were in turn related to a higher number of subsequent (viral) RTIs over the first year of life. Using a multi-omic approach, we found evidence for species-specific host–microbe interactions related to consecutive susceptibility to RTIs. Although further work will be needed to confirm causality of our findings, together these data indicate that early-life viral encounters could impact subsequent host–microbe cross-talk, which is linked to later-life infections. Longitudinal multi-omic analysis of 114 healthy infants from birth to 12 months of age showed that first viral encounters are associated with airway inflammation, changes in respiratory microbiota and later susceptibility to clinical respiratory tract infections.