The Effects of Short-Chain Fatty Acids in Psychosocial Stress-Induced Impairment on Core Executive Functions

Summary

The aim of the present trial is to examine core executive functions (EFs) as a functional outcome of attenuating the cortisol response to acute laboratory stress through colonic delivery of an Short Chain Fatty Acids (SCFAs) mix (acetate, propionate, butyrate).

A triple-blind randomized placebo-controlled parallel group trial will be conducted to compare the effects of SCFAs vs. placebo on core EFs (working memory \[WM\], cognitive flexibility \[CF\], response inhibition \[RI\]) under stress vs. no-stress conditions, after one week of SCFA vs. placebo treatment.

First, the effects of SCFAs on stress-induced changes in core executive functions, with WM as the primary outcome, and CF and RI as secondary outcomes will be tested. Second, interindividual differences in microbiota composition (particularly abundance of SCFA-producers), saliva cortisol and serum SCFA levels will be explored to assess whether they are associated with interindividual differences in core EFs at baseline or following acute stress.

Each participant will undergo 2 study visits: one will involve a stress condition and the other will involve a no-stress condition. Each study visit is preceded by a 1-week intervention or placebo period and separated by a 3-4 week washout period. To induce stress, participants will perform the Maastricht Acute Stress Task (MAST) or sham MAST as the control condition. To assess EF performance, three cognitive tasks will be performed 15 minutes after task offset: n-back task for WM; Stop Signal Task for RI; and Wisconsin Card Sorting Test for CF. Saliva samples will be collected before, during and after the (sham) MAST to assess the cortisol response. Blood samples will be collected throughout all study visits to quantify serum SCFAs, inflammatory markers and ACTH. Additionally, cardiovascular variables will be measured, and self-report questionnaires will be completed to evaluate autonomic response to the condition and subjective stress responses, respectively

Conditions

• Executive Function

Interventions

DIETARY_SUPPLEMENT

Short Chain Fatty Acids (SCFAs).

Colon-delivery capsules of SCFAs.

DIETARY_SUPPLEMENT

Placebo

Microcrystaline cellulose placebo capsules.

OTHER

Maastricht Acute Stress Task

The Maastricht Acute Stress Task. This 15-minute stress-inducing task consists of a 5-minute preparation phase where instructions about the upcoming tasks are given, followed by a 10-minute acute stress phase where the hand immersion trial (HIT) in ice-cold water and mental arithmetic (MA) task is given interchangeably.

OTHER

No-stress control task

The placebo version of the MAST follows the same structure of the MAST with none of the stress elements. It uses lukewarm water and simple arithmetic's.

Sponsors & Collaborators

• United States Department of Defense

  collaborator FED

• Universitaire Ziekenhuizen KU Leuven

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

OTHER

Masking

TRIPLE

Model

PARALLEL

Eligibility

Min Age

20 Years

Max Age

40 Years

Sex

MALE

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2024-07-31

Primary Completion

2025-09-30

Completion

2025-11-30