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

Abstract

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.