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Title: The impact of respiratory viral infections on the gut microbiota
Author: Groves, Helen
ISNI:       0000 0004 8504 700X
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2019
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The gut microbiota has far-reaching effects on health and may influence immune responses in the airways through the gut/lung axis and yet, despite their high prevalence, little is known about how respiratory viral infections affect the gut microbiota. This study investigated the effect of respiratory syncytial virus (RSV) and influenza A virus infection on the gut microbiota using mouse models and 16S rRNA gene sequencing on faecal samples. RSV and influenza virus infection were both associated with an acute significant shift in gut microbiota composition and an increase in the Bacteroidetes to Firmicutes ratio. There was no gut inflammation following respiratory viral infection, although an increase in airway-associated Mucin5ac in the gut was observed. A common symptom of respiratory viral infection in mice is weight loss. Respiratory viral infections reduced food intake in mice and the same gut microbiota changes were observed in fasted mice as detected during respiratory viral infection, suggesting infection-induced inappetence drove changes in the gut microbiota. Both the acute TNF-α and CD8+ T cell response had a role in regulating food consumption during RSV infection but only depleting CD8+ T cells prevented inappetence and weight loss and reversed changes in the gut microbiota during infection. Whether inappetence and associated gut microbiota changes are beneficial or detrimental in the response to infection has yet to be determined. The faecal metabolomic profile was also significantly altered following RSV infection, suggesting an effect on host metabolism and/or gut microbiota metabolism. In spite of altering the gut microbiome, RSV infection was not found to increase susceptibility to gut infection with the pathogen Citrobacter Rodentium. This work demonstrates respiratory viral infections have a significant impact on the composition, and potentially function, of the gut microbiota and therefore may have wider-ranging effects on health than previously thought. By showing the gut/lung axis is bidirectional this may help develop therapies for respiratory viral infection.
Supervisor: Tregoning, John ; Cox, Michael ; Moffatt, Miriam Sponsor: Medical Research Council
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral