Figure 1.

Gaucher disease (GD) flies, lacking Gba1b, the main fly orthologue of GBA1, display widespread lysosomal and autophagy defects, including in the gut wall. In response to pathogenic stimulation by the microbiome, NF-$\mathit{k}$B immune signaling is activated, leading to increased damage associated molecular patterns (DAMPs) and secreted immune mediators called antimicrobial peptides (AMPs). This is locally associated with intestinal microbiome dysbiosis and gut dysfunction. Eradicating the gut microbiome with antibiotic treatment or stimulating autophagy, and possibly other pathways, by treating GD flies with rapamycin, lowers intestinal NF-$\mathit{k}$B signaling, promoting organismal health. Created using Biorender.