Notably, the deficit of SCFAs (metabolites of fiber by gut microbiota) was involved in mediating the gut-brain dysfunction in FD mice; SCFA supplementation prevented the leaky gut and cognitive decline of FD mice and the SCFA receptor knockout (GPR41−/−, 43−/−) mice showed abnormal gut-hippocampal synaptic axis. The gene discussed is FFAR3; the disease is Fabry disease.