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.

Anisha Wijeyesekera, Stephan Theis, Peter Pj Jackson, Claire M Williams, Jessica van Harsselaar, Robert A Rastall

Journal: The American journal of clinical nutrition 2023;118(5):938-955

PMID: 37657523

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Plain Language Summary

Anxiety and depression are the most common mental health disorders and a bidirectional relationship exists between the gut and the brain, the gut-brain axis, which may be mediated by metabolites of the gut microbiome, which include various neurotransmitters. Prebiotics, such as 2'fucosyllactose (2FS, a human milk oligosaccharide) and oligofructose (OF, an inulin-type fructan) can modulate the microbiome and may as such affect mood. The aim of this double-blind, randomised-controlled trial, including 96 healthy adults with mild/moderate levels of stress/anxiety, was to evaluate the effect of a 4-week course of 2FS and OF individually and combined versus maltodextrin (as a placebo) on the microbiome and mood. Significant positive changes in the microbiome were seen in the OF and the OF+2FS groups, compared to control. Improvements in mood (anxiety, depression, positive and negative affect and cortisol awakening response) were seen in all 3 intervention groups compared to control but generally stronger in the OF and the OF+2FS groups. The authors concluded that OF alone and in combination with 2FS has beneficial effects for mood and microbiome composition, whilst the effects on the microbiome of 2FS alone require further study.

Abstract

BACKGROUND

There is increasing interest in the bidirectional 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.

OBJECTIVES

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.

METHODS

We conducted a 5-wk, 4-arm, parallel, double-blind, randomized, placebo-controlled trial in 92 healthy adults with mild-to-moderate levels of anxiety and depression. Subjects were randomized to oligofructose 8 g/d (plus 2 g/d maltodextrin); maltodextrin 10 g/d; oligofructose 8 g/d plus 2'fucosyllactose (2 g/d) or 2'fucosyllactose 2 g/d (plus 8 g/d maltodextrin). Changes in microbial load (fluorescence in situ hybridization-flow cytometry) and composition (16S ribosomal RNA sequencing) were the primary outcomes. Secondary outcomes included gastrointestinal sensations, bowel habits, and mood state parameters.

RESULTS

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, 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).

CONCLUSION

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. This trial was registered at clinicaltrials.gov as NCT05212545.

Address: Department of Food and Nutritional Sciences, University of Reading, Reading, United Kingdom.; University of Reading, School of Psychology and Clinical Language Science, Reading, United Kingdom.; BENEO-Institute, BENEO GmbH, Obrigheim, Germany.; Department of Food and Nutritional Sciences, University of Reading, Reading, United Kingdom. Electronic address: [email protected].

DOI: 10.1016/j.ajcnut.2023.08.016