Minocycline-induced microbiome alterations predict cafeteria diet-induced spatial recognition memory impairments in rats

Abstract

Diets rich in sugar and saturated fat are associated with cognitive impairments in both humans and rodents with several potential mechanisms proposed. To test the involvement of diet-induced pro-inflammatory signaling, we exposed rats to a high-fat, high-sugar cafeteria diet, and administered the anti-inflammatory antibiotic minocycline. In the first experiment minocycline was coadministered across the diet, then in a second, independent cohort it was introduced following 4 weeks of cafeteria diet. Cafeteria diet impaired novel place recognition memory throughout the study. Minocycline not only prevented impairment in spatial recognition memory but also reversed impairment established in rats following 4 weeks cafeteria diet. Further, minocycline normalized diet-induced increases in hippocampal pro-inflammatory gene expression. No effects of minocycline were seen on adiposity or dietary intake across the experiments. Cafeteria diet and minocycline treatment significantly altered microbiome composition. The relative abundance of Desulfovibrio_OTU31, uniquely enriched in vehicle-treated cafeteria-fed rats, negatively and significantly correlated with spatial recognition memory. We developed a statistical model that accurately predicts spatial recognition memory based on Desulfovibrio_OTU31 relative abundance and fat mass. Thus, our results show that minocycline prevents and reverses a dietary-induced diet impairment in spatial recognition memory, and that spatial recognition performance is best predicted by changes in body composition and Desulfovibrio_OTU31, rather than changes in pro-inflammatory gene expression.

Gut microbial taxa elevated by dietary sugar disrupt memory function

“…Dietary factors are a key source of gut microbiome diversity 28,46,[61][62][63] and emerging evidence indicates that diet-induced alterations in the gut microbiota may be linked with altered neurocognitive development 28,[63][64][65] . Our results identify species within the genus Parabacteroides that are elevated by habitual early life consumption of dietary sugar and are negatively associated with hippocampal-dependent memory performance.…”

Minocycline Reduces Hypothalamic Microglia Activation and Improves Metabolic Dysfunction in High Fat Diet-Induced Obese Mice

“…We speculate these findings suggest that beneficial effects of minocycline on HFD-induced metabolic dysfunction may be regulated, at least in part, via selective reductions in PVN neuroinflammatory processes. Although not tested here, minocycline has been suggested to modulate high fat diet outcomes via alteration of the gut microbiome ( Hasebe et al, 2019 ; Leigh et al, 2020 ; Vaughn et al, 2017 ), which has also been shown to alter neuroinflammatory signaling ( Haase et al, 2020 ; Rea et al, 2016 ; Rutsch et al, 2020 ).…”

Nrf2/ARE Activators Improve Memory in Aged Mice via Maintaining of Mitochondrial Quality Control of Brain and the Modulation of Gut Microbiome

“…Odoribacter level increased significantly in APP/PS1 [ 72 ] and aged [ 73 ] mice with impaired spatial learning. Desulfovibrio was also associated with memory decline, induced by a high-fat diet [ 74 , 75 ]. At the same time, some of our data are at odds with the previously obtained results.…”