Minocycline Prevention and Reversal Study

Obesogenic diets and obesity are associated with cognitive impairment in both humans and animals. While the underlying mechanisms remain controversial, a key potential driver is increased inflammatory signaling associated with obesity. The anti-inflammatory antibiotic minocycline hydrochloride has been routinely used to depress microglial activity as it easily crosses the blood brain barrier. Here, we used a rodent model to show that minocycline treatment (40mg/kg/day) prevented spatial recognition memory impairment and hippocampal pro-inflammatory gene expression induced by a high-fat high-sugar “cafeteria” diet, without affecting adiposity. Minocycline and cafeteria diet significantly reduced measures of alpha diversity and interacted to significantly alter microbiome composition. Additionally, we showed that minocycline treatment in already obese rats improved impaired spatial recognition memory. Desulfovibrio_OTU31, identified as a strain of Desulfovibrio piger, was uniquely enriched in vehicle-treated cafeteria-fed rats and was significantly correlated with spatial recognition memory across two independent cohorts. We develop a model that accurately predicts spatial recognition memory based on Desulfovibrio_OTU31 and fat mass. In summary, we show that minocycline improves spatial recognition memory impairments observed in rats fed a cafeteria diet, and these behavioral differences are best predicted by changes in body composition and Desulfovibrio_OTU31, rather than hippocampal gene expression.