Effects of a flavonoid-rich blackcurrant beverage on markers of the gut-brain axis in healthy females: Secondary findings from a 4-week randomized crossover control trial.

The microbiota-gut-brain axis is a promising target to alleviate the growing burden of neurological and mental health disorders. Dietary polyphenols act on multiple components of the microbiota-gut-brain axis, but this complex relationship requires further attention. This randomized, placebo-controlled, double-blind, crossover trial (ACTRN12622000850774) compared 4-weeks of a commercially-available flavonoid-rich blackcurrant beverage (FBB, 151 mg anthocyanins, 308 mg total polyphenols) versus placebo in 40 healthy females (18-45y). The primary outcome of stress reactivity was assessed by change in present feelings of stress, mood and fatigue before and after completing a 20-minute cognitive stressor (Purple multi-tasking framework, MTF). Secondary endpoints included cognitive performance (MTF), mood (Profile of Mood States, POMS), sleep (Pittsburgh Sleep Quality Index), fecal microbiome composition and functional potential (shotgun sequencing) and blood biomarker concentrations (Brain Derived Neurotrophic Factor, tryptophan, kynurenine, interleukin-6). Statistical analyses were conducted on an intention-to-treat basis using linear mixed-effect models. Thirty-eight participants completed both intervention arms. There was no significant treatment effect on the primary outcome of stress reactivity. Compared with placebo, working memory (letter retrieval scores, MTF), and ‘anxiety/tension’ and ‘anger/hostility’ domains of the POMS improved with FBB supplementation (time x intervention interaction, p<0.05). There were no treatment effects on gut microbiome composition or functional potential. Baseline abundances of Bifidobacterium genera and species (B. longum, B. bifidum) tended to be higher in participants with the greatest improvements in letter retrieval scores with FBB supplementation (nominally significant, p<0.05). In conclusion, 4-weeks of FBB supplementation improved secondary outcomes of working memory performance during multi-tasking and mood outcomes in healthy adult females. These results should be confirmed in a larger cohort with a longer duration of follow-up.