Bifidobacterium breve CCFM1179 Modulates Gut Microbiota and Improves Mild Cognitive Impairment: A Randomized, Double-Blind, Placebo-Controlled Trial

Mild cognitive impairment (MCI) represents a critical transitional phase in Alzheimer's disease progression and constitutes a vital intervention window for delaying disease onset. With accelerating population aging, the demand for MCI prevention and management has become increasingly urgent, rendering the exploration of safe and effective early interventions of substantial clinical and societal importance. Building upon prior animal studies demonstrating the cognitive-enhancing potential of Bifidobacterium breve CCFM1179, this randomized, double-blind, placebo-controlled trial evaluated its clinical efficacy through a 12-week intervention in MCI subjects. Concurrently, alterations in gut microbiota, serum, and fecal metabolites were examined to elucidate potential mechanisms. Results demonstrated that compared with placebo, CCFM1179 significantly improved Montreal Cognitive Assessment scores, particularly in visuospatial/executive and naming domains, accompanied by elevated serum brain-derived neurotrophic factor (BDNF) levels. Gut microbiota α-diversity remained stable, yet β-diversity exhibited marked separation. Post-intervention abundance increased in genera including Prevotella, Coprococcus, and Barnesiella, whereas Megamonas, a genus associated with metabolic abnormalities, decreased. Metabolomic analyses revealed substantial alterations in both gut and serum metabolites, with differences predominantly concentrated in amino acid and tryptophan metabolic pathways. Notably, elevated levels of indole-3-propionic acid (IPA) and indole-3-carboxaldehyde (IAld) correlated positively with BDNF, while quinolinic acid decreased. These findings suggest that Bifidobacterium breve may enhance cognitive function by promoting protective indole-derived metabolic pathways and modulating gut-brain axis metabolic signaling. This study provides clinical evidence supporting microbiome-based interventions for MCI and highlights the potentially central role of tryptophan metabolism in cognitive improvement.