Role of Microbiota in development, gene expression and epigenetic modifications in D. melanogaster host model

Eukaryotes and prokaryotes have developed mutually beneficial relationships over millennia of evolutionary adaptation. Recent observations suggest a strong correlation between the presence of Microbiota and host homeostasis, but little is known about the mechanisms they use to shape the physiology and to reprogram gene expression of their host. Using both conventionally reared and germ-free D. melanogaster as a model system, I found a role of bacteria in host protein expression and development, as germ-free flies develop more slowly than their conventional counterpart. Remarkably, using the classic variegated In(1)wm4 inversion, I identified a role of Microbiota as modifier of white Position Effect Variegation (PEV). This data strongly indicated that the presence of the Microbiota may change the epigenetic state of the fly genome. In order to characterize at the molecular level the effect of bacteria on white PEV, I took advantage of the powerful tool of Next Generation Sequencing (NGS) to analyze the transcriptomes of germ-free and conventional flies, and I found remarkable differences between the two conditions, with a strong impact of bacteria at all metabolic levels. Moreover, to identify and quantify the epigenetic changes promoted by bacteria, I conducted ChIP-seq analysis to study genome-wide the profiles of specific histone modifications and I found a strong correlation between changes in chromatin hallmarks and differentially expressed genes. My study has led to the identification of bacteria as a powerful and important factor controlling host gene expression through chromatin remodeling, thus influencing host homeostasis and development, but biochemistry and molecular assays still have to be done on differentially expressed genes, in order to confirm they have different profiles of histone modifications and, thus, different chromatin structures. Taken together my data provide crucial insights into a new unexplored role of the Microbiota in host regulation of chromatin structure, epigenetic programming and homeostasis.