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Drosophila models of intestinal inflammation and cancer

European scientists worked towards a deeper understanding of intestinal human disease, inflammation and tumour formation.
Drosophila models of intestinal inflammation and cancer
Intestinal disease is often caused by pathogenic microbes, which perturb epithelial homeostasis, causing inflammation and innate immune response impairment. The molecular nature of the relationship between microbial infection, inflammation and cancer, however, remains elusive.

Considering the evolutionarily conserved pathways of innate immune signalling and carcinogenesis, Drosophila is a suitable model for studying human processes. The EU-funded INFECTIONCANCER (Identifying genetic and microbial factors that promote intestinal inflammation and cancer using Drosophila) project exploited Drosophila as a genetically tractable model system of inflammation and carcinogenesis.

Previous work by the consortium had shown that virulent bacteria induced enterocyte apoptosis and activated endogenous stem cells to replenish the dying cells. Depending on the genetic background, this process could lead to tumour formation and growth. Scientists investigated intestinal dysplasia-prone infected flies for differentially expressed genes that could participate in the interaction between infection and tumour development.

In addition to genetic factors, researchers discovered that diet and intestinal bacteria also affect tumour metastasis. They observed that intestinal microbes such as P. aeruginosa and E. coli interacted with each other and with the host to induce or even inhibit inflammation. Importantly, they uncovered microbiota compositions that affected intestinal inflammation and strongly correlated with particular disease states.

To delineate if these changes constituted a true cause of intestinal inflammation, they assessed the potential of various intestinal bacteria combinations to induce inflammation and disease. They found that certain bacteria including P. aeruginosa and E. coli excreted metabolites that could directly induce inflammation.

Taken together, the results of INFECTIONCANCER provide a direct link between the presence of certain intestinal bacteria and inflammation. Considering the increasing prevalence of intestinal diseases and cancer, the generated information could help in the development of preventative measures or the design of novel therapeutic interventions.

Related information

Keywords

Drosophila, intestinal inflammation, cancer, gene, P. aeruginosa, E. coli, microbiota
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