Gut Microbial Release of Ferulic Acid From Germinated Quinoa Alleviates Obesity-Associated Cognitive Impairment by Activating Hippocampal Mitophagy Associated with PINK1/Parkin Pathway.

Obesity is a major risk factor for cognitive impairment and related neurodegenerative disorders. Whole grains are rich in polyphenols and dietary fiber, with intake associated with improvements in obesity and cognitive deficits. Gut microbial genes encode enzymes that metabolize dietary polyphenols, thereby influencing host metabolic and neurological health; however, the specific functional microbes and enzymes involved remain largely unknown. Here, we demonstrate that germinated quinoa (GQF), a polyphenol-enriched whole-grain intervention, alleviates high-fat diet-induced cognitive impairment and restores gut microbial diversity more effectively than native quinoa (QF). These benefits correlate with enriched Roseburia abundance and enhanced carbohydrate-active enzyme (CAZyme) gene profiles, particularly genes encoding feruloyl esterase (FAE). GQF exerts neuroprotective effects via a microbiota-substrate co-dependent pattern, rather than simply relying on gut microbiota alone. Specifically, GQF selectively promotes FAE-harboring Roseburia hominis and R. intestinalis proliferation, thereby facilitating the release of bound ferulic acid (FA) from GQF. Liberated FA promotes neuronal growth and synaptic plasticity by activating PINK1/Parkin-dependent hippocampal mitophagy. These results underscore the indispensable role of specific gut microbes in unlocking the nutritional efficacy of GQF. In conclusion, dietary GQF and its microbe-releasable FA represent a natural nutritional strategy, providing a promising preventive and adjuvant approach for metabolic-related cognitive dysfunction.