Host-gut microbiota interaction in health and disease using Drosophila melanogaster as a model organism

Thesis

The resident gut bacteria of the gastrointestinal tract (gut microbiota) have been known to influence the immune system. Yet the role of the immune system in shaping the gut microbiota composition across an organism’s lifespan remains unclear. Previous work in mice has been conflicting and thus remains inconclusive. Here, Drosophila melanogaster was used as a model organism with a simpler gut commensal community to address this issue. Using four strains of Drosophila reflecting different immune statuses, we found that wild type and immune-compromised strains had the same Acetobacteraceae-dominant pattern across their adult lifespan. However, flies with a constitutively active immune system had a distinctive gut microbiota structure that persisted even when maternally transmitted bacteria were removed and was distinguishable from its genetic background.

Additionally, co-housing experiments showed that the local environment also played an important role in gut microbiota composition. When the physiology of the gut was explored, it showed that the gut internal environment was affected as a consequence of having a de-regulated immune system. Together, our results in Drosophila showed that a constantly active immune system shaped microbiota in the gastrointestinal tract. Given the evolutionary conservation of innate immunity between insects and mammals our data has implications for the shaping of the gut microbiota structure in humans with a chronically inflamed intestine.

Authors: Mistry, R

• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford