Gut & Microbiome

Gut Bacteria Compound Ergothioneine May Reverse Antipsychotic Brain Damage

Researchers discovered that common antipsychotic drugs like olanzapine, risperidone, and clozapine deplete a gut-bacteria-derived compound called ergothioneine, which normally protects the brain. In mice, chronic antipsychotic use disrupted the gut microbiome, damaged the intestinal barrier, and caused measurable cognitive decline. Multi-omics analysis showed ergothioneine was severely reduced in blood and brain tissue — a finding confirmed in human patients on olanzapine. When ergothioneine was supplemented, cognitive impairment was reversed. The mechanism involves reduced oxidative stress in the hippocampus and inhibition of a damaging enzyme called PTP1B. These findings suggest ergothioneine supplementation could be a practical strategy to protect brain health in the millions of people taking antipsychotic medications long-term.