AbstractBackgroundTo analyze the concept of whether enteric dysbiosis contributes to the aggravation of tau protein, Drosophila melanogaster was used as a transgenic model organism. To study how the exposure of Pseudomonas sp., a gram‐negative bacteria, influences tau accumulation and neurodegeneration thereby understanding the gut‐brain correlation for the pathology of Alzheimer’s Disease.MethodThe versatile Gal4‐UAS gene expression system was used to express wild‐type tau with the help of pan‐eye specific GMR‐Gal4 in the flies. All the flies were exposed to Pseudomonas sp. to initiate the gut microbial dysbiosis. The extent of neurodegeneration was quantified by automated analysis of the degenerated region in the eye, the number of aggregates, and immunofluorescence quantification in the medulla. To understand the response of glial cells upon bacterial infection in tauopathy‐related dementia, tau was driven by glia‐specific Repo‐GAL4. Similarly, neuroinflammation which is found in tauopathies was studied using an eye‐specific driver line GMR‐GAL4, UAS‐ eiger/CyO.ResultUpon exposure of Pseudomonas sp. on the wild type tau (tauwt) around the medulla, the degeneration was faster and, there was an increase in the levels of tau as compared to the control. Downregulation of Atg 1 and Atg 18 gene along with significant upregulation of Atg 12 is observed in tau expressing infected flies compared to tau expressing control flies. There was a significant degeneration as well as an increase in the number of aggregates in the medulla of the optic lobe. Similar degeneration was observed in flies expressing tauwt and egr along with an increased accumulation of tau in both retina and medulla.ConclusionWhen the flies expressing tau are subjected to the pathogen, and aggravation in tau accumulation is observed along with neuroinflammation and changes in the homeostasis. Due to its role in maintaining of body’s homeostasis, the gut‐brain correlation can have both detrimental and beneficial effects on the brain and the survival of neurons.