Characterization of the Diet-Microbiota-Gut-Brain Axis and its Role in Neuroinflammation

Abstract

Neurodegenerative Diseases (NDs) are the leading causes of disability/death globally. The Diet-Microbiota-Gut-Brain (DMGB) axis is a promising area of research for NDs, investigating how intercommunication between diet, intestinal microbiota, and the intestinal epithelium distally affects the brain. NDs also co-appear with perturbed metabolic and oxidative regulators in the gut, such as peroxisome organelles, that control tissue integrity and commensal populations. Therefore, I hypothesized that peroxisomes in the gut are important modulators of the DMGB axis. Recruiting the Drosophila melanogaster (fruit fly) as my model, I depleted peroxisome function in the animal’s intestinal epithelium (midgut), which effected climbing behaviour, accompanied by redox stress, inflammation and cellular death throughout the brain over aging. I also screened these midguts for peroxisome-dependent transcription factors that control DMGB axis communication, and identified Myo-inhibitory peptide (Mip) expression corresponding to the climbing deficit that was observed. Therefore, Mip in the DMGB axis of Drosophila requires further investigation.