Exploring the effect of the oropharyngeal host microbiota on host response during viral infection
File(s)
Author(s)
Kavanagh, James
Type
Thesis or dissertation
Abstract
The respiratory microbiota plays a key role in shaping the immune response of children to viral respiratory tract infections (RTIs). The oropharynx, a previously understudied site for microbiota research, harbours a diverse and clinically significant microbial community. Characterising the composition of the oropharyngeal microbiota during viral RTIs, and understanding how it correlates with clinical severity and inflammatory response, can provide important insights into disease prevention, progression and diagnostics.
Using Oxford Nanopore Technologies 16S rRNA gene sequencing, I characterised the oropharyngeal microbiota of 233 paediatric patient samples collected through two multi-site international studies, PERFORM and DIAMONDS, focussing on patients with respiratory syncytial virus (RSV), Influenza or Adenovirus. Combining patient microbiota profiles with detailed clinical metadata, I investigated associations between disease severity and inflammatory response with the overall microbiota diversity, community structure and the presence of individual taxa previously linked to respiratory health.
While no association was observed between microbiota alpha diversity and disease severity, the presence of Moraxella and Haemophilus were associated with reduced severity across all viral groups. Severity and age group were strongly associated with community composition in RSV and Adenovirus patients. In RSV patients, Streptococcus salivarius and Streptococcus oralis were linked to reduced severity. No significant associations were found between CRP and any measured marker of microbiota composition or diversity.
Overall, this thesis provides evidence for viral-specific associations between oropharyngeal microbiota composition and clinical severity, even when accounting for the effects of age, and suggests specific taxa as candidate biomarkers of clinical severity in patients with viral RTIs. It also demonstrates the importance of niche-specific studies of the respiratory microbiota during viral RTIs, and highlights inconsistencies between microbiome research studies and underlying issues with reproducibility which need to be addressed before incorporating into clinical diagnostics.
Using Oxford Nanopore Technologies 16S rRNA gene sequencing, I characterised the oropharyngeal microbiota of 233 paediatric patient samples collected through two multi-site international studies, PERFORM and DIAMONDS, focussing on patients with respiratory syncytial virus (RSV), Influenza or Adenovirus. Combining patient microbiota profiles with detailed clinical metadata, I investigated associations between disease severity and inflammatory response with the overall microbiota diversity, community structure and the presence of individual taxa previously linked to respiratory health.
While no association was observed between microbiota alpha diversity and disease severity, the presence of Moraxella and Haemophilus were associated with reduced severity across all viral groups. Severity and age group were strongly associated with community composition in RSV and Adenovirus patients. In RSV patients, Streptococcus salivarius and Streptococcus oralis were linked to reduced severity. No significant associations were found between CRP and any measured marker of microbiota composition or diversity.
Overall, this thesis provides evidence for viral-specific associations between oropharyngeal microbiota composition and clinical severity, even when accounting for the effects of age, and suggests specific taxa as candidate biomarkers of clinical severity in patients with viral RTIs. It also demonstrates the importance of niche-specific studies of the respiratory microbiota during viral RTIs, and highlights inconsistencies between microbiome research studies and underlying issues with reproducibility which need to be addressed before incorporating into clinical diagnostics.
Version
Open Access
Date Issued
2025-10-20
Date Awarded
2026-07-01
Copyright Statement
Attribution-NonCommercial 4.0 International Licence (CC BY-NC)
License URL
Advisor
Levin, Mike
Kaforou, Myrsini
Shaw, Alex
Sponsor
Medical Research Council (Great Britain)
Grant Number
WDPI_G98687_169204
Publisher Department
Department of Infectious Disease
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)