Fig. 1

Illustration of GUMBA in development of neuropathology in humans and fruit flies. Changes in the GM composition and resultant altered gut-derived microbial products and neurotransmission can over-activate the immune system producing increased oxidative stress. Sustained oxidative stress can increase intestinal permeability and inflammation, thus triggering systemic inflammation, which can enhance the blood-brain barrier permeability and cause microglial activation in the brain through the transport of immune cells and metabolites via the systemic route. This would, in turn, enhance oxidative stress and exacerbate neuroinflammation in the brain, resulting in disease pathophysiology and abnormal behavior. Changes in GM composition and its metabolites can also alter vagus nerve signaling and exert effects on the brain and behavior. Many organ systems are homologous between humans and flies; however, the mechanistic basis of GUMBA involvement in neuropathology development remains to be uncovered in flies. SEO, serotonergic output; AN, antennal nerve (Created with BioRender.com)