Inulin-type fructans and 2’fucosyllactose alter both microbial composition and appear to alleviate stress-induced mood state in a working population compared to placebo (maltodextrin): the EFFICAD Trial, a randomized, controlled trial

There is increasing interest in the bi-directional relationship existing between the gut and brain and the effects of both oligofructose and 2’fucosyllactose to alter microbial composition and mood state. Yet, much remains unknown about the ability of oligofructose and 2’fucosyllactose to improve mood state via targeted manipulation of the gut microbiota. We aimed to compare the effects of oligofructose and 2’fucosyllactose alone and in combination against maltodextrin (comparator) on microbial composition and mood state in a working population. We conducted a 5-week, 4-arm, parallel, double-blind, randomised, placebo-controlled trial in 92 healthy adults with mild-to-moderate levels of anxiety and depression. Subjects were randomised to oligofructose 8 g/day (plus 2 g/day maltodextrin); maltodextrin 10 g/day; oligofructose 8 g/day plus 2’fucosyllactose (2 g/day) or 2’fucosyllactose 2 g/day plus (8 g/day maltodextrin). Changes in microbial load (FISH-FLOW) and composition (16s rRNA sequencing) were the primary outcomes. Secondary outcomes included gastrointestinal sensations, bowel habits and mood state parameters. There were significant increases in several bacterial taxa including Bifidobacterium, Bacteroides, Roseburia and Faecalibacterium prausnitzii in both the oligofructose and oligofructose/2’fucosyllactose interventions (all P ≤ 0.05). Changes in bacterial taxa were highly heterogenous upon 2’fuscoyllactose supplementation. Significant improvements in Beck Depression Inventory, State Trait Anxiety Inventory Y1 and Y2, and Positive and Negative Affect Schedule scores and cortisol awakening response were detected across oligofructose, and 2’fucosyllactose and oligofructose/2’fucosyllactose combination interventions (all P ≤ 0.05). Both sole oligofructose and oligofructose/2’fuscosyllactose combination interventions outperformed both sole 2’fucosyllactose and maltodextrin in improvements in several mood state parameters (all P ≤ 0.05). The results of this study indicate that oligofructose and combination of oligofructose/2’fucosyllactose, can beneficially alter microbial composition along with improving mood state parameters. Future work is needed to understand key microbial differences separating individual responses to 2’fucosyllactose supplementation. ClinicalTrials.gov (https://clinicaltrials.gov/ct2/show/NCT05212545): NCT05212545