A randomised controlled trial of the effects of Galacto-Oligosaccharides on the gut brain-axis of young females

Galacto-oligosaccharides (GOS) are prebiotics that modulate gut microbiota and are implicated in the gut-brain axis (GBA), with preclinical models reporting effects on neurochemistry, brain function, and cognition. Here we report the results of a randomised, double-blind, placebo-controlled trial in 83 healthy females (17-25 years), who received GOS or placebo for 28 days. Assessments occurred at baseline, endline, and 28 days post-supplementation. The primary outcome was trait anxiety, secondary outcomes were brain-based levels of GABA and glutamate in the dorsolateral prefrontal cortex (dlPFC), anterior cingulate cortex, and inferior occipital gyrus (IOG) (measured with ¹H-MRS), and gut microbiome composition. Tertiary outcomes included social anxiety, depression, emotion behaviour, reaction times, and nutritional intake. Analyses included intention-to-treat, per-protocol, and sensitivity approaches. Trait anxiety did not differ between groups at endline (p = 0.443), though trends favoured lower anxiety in the GOS group at follow-up (p = 0.069). GOS reduced GABA at trend significance in the IOG (p = 0.053) in the Intention to Treat (ITT) population and dlPFC (p = 0.088) in high-anxious participants, with effects persisting at follow-up. GOS transiently increased Bifidobacterium abundance (p = 0.001) but did not affect microbiome diversity. Tertiary outcomes showed no significant changes in social anxiety or depression but faster reaction rates in high-anxious participants for simple (p = 0.036) and choice tasks (p < 0.001). Nutritional intake was unaffected. While GOS supplementation did not significantly reduce trait anxiety, it produced neurochemical changes and transient modulations of the gut microbiome in Bifidobacterium abundance, indicating GOS-induced changes can be traced along the GBA.