THE ROLE OF ENTEROENDOCRINE SECRETED GUT PEPTIDE HORMONES IN MODULATING IMMUNITY AND METABOLISM IN DROSOPHILA MELANOGASTER

Abstract

The intestine of all living organisms fosters an ecosystem of commensal microbiota that plays key roles in the maintenance of host health and pathology. Captivatingly, the influence of dysbiosis on the host has demonstrated the significance of the existing crosstalk between the gut microbiota, nutrient balance, and immune processes. Intestinal enteroendocrine cells (EE)-secreted gut peptide hormones represent an emerging area of exploration, with a gut flora-dependent role in modulating metabolism and innate immune signaling yet to be determined. In this study, we utilize the Drosophila melanogaster model organism to understand the systemic and/or tissue-specific roles of Tachykinin (Tk), Diuretic Hormone 31 (DH31), and Allatostatin A (AstA) EE secreted peptide hormones in maintaining metabolic homeostasis and modulating innate immune signaling. Our findings reveal significant disruptions in gut flora distribution and in several metabolic parameters including: body weight, systemic glucose and triglyceride levels, lipid transport from gut, and fat body lipid storage in three systemic mutant lines (TkEY20174, Dh31KG09001 and AstAMB10261) and in the Tk>AstARNAi transgenic line. We also report altered immune status and host susceptibility profiles TkEY20174, Dh31KG09001, AstAMB10261, and Tk>AstARNAi flies infected with bacteria. Consistent with these results, RNA-sequencing on the whole intestine of these systemic mutants and transgenic flies identified several differentially expressed genes associated with the processes of metabolism and immunity. Together, the findings of this project provide further insight into the contribution of EE-secreted peptide hormones in the maintenance of immune-metabolic homeostasis in a host, a foundation that could have profound implications on the therapy of metabolic and immune illnesses as well as for metabolic ramifications of intestinal dysbiosis.