Gut Microbiota Remodeling Drives Cognitive Improvement: A Microbiota-Dependent Study of Malvidin-3-O-glucoside against Alcohol-Related Cognitive Impairment.

Gut microbiota dysbiosis triggers alcohol-related cognitive impairment (ARCI). Malvidin-3-O-glucoside (Mv3G), a highly bioactive monomeric anthocyanin abundant in pigmented fruits and cereals, can relieve neurodegenerative diseases by regulating gut microbiota (GM). Nevertheless, the gut microbiota-mediated protective effect of Mv3G against ARCI remains unknown. In this study, an alcohol-induced ARCI mouse model combined with fecal microbiota transplantation (FMT) was built to explore Mv3G's protective effects. Results show that Mv3G acts in an intact gut flora-dependent manner. It repairs intestinal injury and restores intestinal barrier by upregulating tight junction proteins ZO-1 and occludin, enriches beneficial bacteria such as Lachnospiraceae_NK4A136_group and Akkermansia, adjusts the Bacteroidetes/Firmicutes ratio, and decreases pathogenic Pseudomonadales to remodel gut microbiota. Via the gut-brain axis, Mv3G suppresses central inflammation, maintains hippocampal synapses and improves cognitive performance. In vitro experiments further confirm that Mv3G alleviates ARCI relying on gut microbiota. This research provides a novel intervention strategy for alcohol-induced cognitive injury.