Le Duc Huy Ta1, Gaik Chin Yap1, Carina Jing Xuan Tay1, Alicia Shi Min Lim1, Chiung-Hui Huang1, Collins Wenhan Chu2, Paola Florez De Sessions2, Lynette P Shek3, Anne Goh4, Hugo P S Van Bever3, Oon Hoe Teoh4, Jian Yi Soh3, Biju Thomas4, Mahesh Babu Ramamurthy3, Daniel Y T Goh3, Christophe Lay5, Shu-E Soh1, Yiong Huak Chan6, Seang-Mei Saw7, Kenneth Kwek8, Yap-Seng Chong9, Keith M Godfrey10, Martin Lloyd Hibberd2, Bee Wah Lee11. 1. Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. 2. Genome Institute of Singapore, Agency for Science, Technology and Research Singapore, Singapore. 3. Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Khoo Teck Puat-National University Children's Medical Institute, National University Health System, Singapore. 4. Department of Paediatrics, KK Women's and Children's Hospital, Singapore. 5. Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Danone Nutricia Research, Singapore. 6. Biostatistics Unit, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. 7. Saw Swee Hock School of Public Health, National University of Singapore, Singapore. 8. Department of Maternal Fetal Medicine, KK Women's and Children's Hospital, Singapore. 9. Department of Obstetrics & Gynaecology, National University of Singapore, Singapore; Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research Singapore, Singapore. 10. MRC Lifecourse Epidemiology Unit and NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom. 11. Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. Electronic address: paeleebw@nus.edu.sg.
Abstract
BACKGROUND: Dynamic establishment of the nasal microbiota in early life influences local mucosal immune responses and susceptibility to childhood respiratory disorders. OBJECTIVE: The aim of this case-control study was to monitor, evaluate, and compare development of the nasal microbiota of infants with rhinitis and wheeze in the first 18 months of life with those of healthy control subjects. METHODS: Anterior nasal swabs of 122 subjects belonging to the Growing Up in Singapore Towards Healthy Outcomes (GUSTO) birth cohort were collected longitudinally over 7 time points in the first 18 months of life. Nasal microbiota signatures were analyzed by using 16S rRNA multiplexed pair-end sequencing from 3 clinical groups: (1) patients with rhinitis alone (n = 28), (2) patients with rhinitis with concomitant wheeze (n = 34), and (3) healthy control subjects (n = 60). RESULTS: Maturation of the nasal microbiome followed distinctive patterns in infants from both rhinitis groups compared with control subjects. Bacterial diversity increased over the period of 18 months of life in control infants, whereas infants with rhinitis showed a decreasing trend (P < .05). An increase in abundance of the Oxalobacteraceae family (Proteobacteria phylum) and Aerococcaceae family (Firmicutes phylum) was associated with rhinitis and concomitant wheeze (adjusted P < .01), whereas the Corynebacteriaceae family (Actinobacteria phylum) and early colonization with the Staphylococcaceae family (Firmicutes phylum; 3 weeks until 9 months) were associated with control subjects (adjusted P < .05). The only difference between the rhinitis and control groups was a reduced abundance of the Corynebacteriaceae family (adjusted P < .05). Determinants of nasal microbiota succession included sex, mode of delivery, presence of siblings, and infant care attendance. CONCLUSION: Our results support the hypothesis that the nasal microbiome is involved in development of early-onset rhinitis and wheeze in infants.
BACKGROUND: Dynamic establishment of the nasal microbiota in early life influences local mucosal immune responses and susceptibility to childhood respiratory disorders. OBJECTIVE: The aim of this case-control study was to monitor, evaluate, and compare development of the nasal microbiota of infants with rhinitis and wheeze in the first 18 months of life with those of healthy control subjects. METHODS: Anterior nasal swabs of 122 subjects belonging to the Growing Up in Singapore Towards Healthy Outcomes (GUSTO) birth cohort were collected longitudinally over 7 time points in the first 18 months of life. Nasal microbiota signatures were analyzed by using 16S rRNA multiplexed pair-end sequencing from 3 clinical groups: (1) patients with rhinitis alone (n = 28), (2) patients with rhinitis with concomitant wheeze (n = 34), and (3) healthy control subjects (n = 60). RESULTS: Maturation of the nasal microbiome followed distinctive patterns in infants from both rhinitis groups compared with control subjects. Bacterial diversity increased over the period of 18 months of life in control infants, whereas infants with rhinitis showed a decreasing trend (P < .05). An increase in abundance of the Oxalobacteraceae family (Proteobacteria phylum) and Aerococcaceae family (Firmicutes phylum) was associated with rhinitis and concomitant wheeze (adjusted P < .01), whereas the Corynebacteriaceae family (Actinobacteria phylum) and early colonization with the Staphylococcaceae family (Firmicutes phylum; 3 weeks until 9 months) were associated with control subjects (adjusted P < .05). The only difference between the rhinitis and control groups was a reduced abundance of the Corynebacteriaceae family (adjusted P < .05). Determinants of nasal microbiota succession included sex, mode of delivery, presence of siblings, and infant care attendance. CONCLUSION: Our results support the hypothesis that the nasal microbiome is involved in development of early-onset rhinitis and wheeze in infants.
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