Butyrate has been identified as a high-affinity ligand for the Gi-linked heterotrimeric guanine nucleotide-binding protein–coupled receptor (GPCR) hydroxycarboxylic acid receptor 2 (HCAR2) (Carretta et al, 2021), which is expressed in the brain and has been shown to modulate microglial actions in several neuroinflammatory diseases such as multiple sclerosis, Parkinson’s disease, and Alzheimer’s disease (Offermanns, 2014; Moutinho et al, 2022). Here, HCAR2 is linked to Alzheimer disease.