Parkinson’s disease (PD) is the second-most common neurodegenerative disorder worldwide, and a cure remains elusive. Although its hallmarks are motor symptoms resulting from neuronal loss, increasing attention has been paid to the effect of gut microbiota on PD. A recent study examined this connection by focusing on the effect of a unique protein. Osteocalcin (OCN), a protein secreted by osteoblasts during bone formation, can pass through the blood-brain barrier. OCN can modulate brain function, and patients with PD are highly susceptible to osteoporosis, suggesting a link between bone health and PD. Using a mouse model of PD, researchers found that injecting OCN had a protective effect, ameliorating motor deficits and neuronal loss. Antibiotic exposure prior to OCN treatment revealed that this effect was dependent on gut microbiota. OCN altered the abundance of specific microbes, including Bacteroidetes and Firmicutes, in the guts of PD model mice and the microbial changes resulted in increased levels of propionate, a microbial metabolite. A propionate agonist mimicked these protective effects, and ablation of gut neurons blocked the protective effect of propionate on dopaminergic neurons. These results indicate that OCN can modulate the gut microbiome and protect against the effects of PD, suggesting a role for gut microbes and propionate in mediating the neuroprotective effect of osteocalcin from PD progression.