The role of short chain fatty acids (SCFA) in the microbiota-gut-brain axis is examined in a sample of healthy volunteers. SCFA are the major products of bacterial fermentation of dietary fiber in the colon, and are hypothesised to mediate the bidrectional communication between the gut and the residing microbiota on the one hand, and the central nervous system on the other hand. We perform a 1-week intervention with SCFA and measure their effects on a range of affective outcomes in healthy male volunteers.
The study is an interventional double-blind, placebo-controlled, parallel group design with 3 arms (placebo, high-dose of SCFA, and low-dose of SCFA). The high and low doses of SCFA are equivalent to 20 and 10 grams of fiber respectively. Healthy male participants follow a low-fiber diet for the study duration (11 days). On day 4, baseline measurements are taken in the lab, including biological samples and psychophysiological measurements. Participants then consume placebo or SCFA for one week and revisit the lab on day 11 for a second measurement of the outcomes of interest. Specifically, we investigate the effect of SCFA supplementation on affective processing, including stress sensitivity, fear-related processes (e.g. extinction learning), and attentional bias to emotional stimuli. Volunteers also respond to questionnaires in relation to mood, and provide biological samples (blood and faecal samples) for analysis of circulating short chain fatty acids and microbiota composition, respectively.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
SINGLE
Enrollment
66
Intracolonic administration
UZ Leuven/Stresslab
Leuven, Belgium
Stress sensitivity
Induction of cognitive, physical, and social stress using Maastricht Acute Stress Test. Stress hormone cortisol is quantified.
Time frame: 1 year
Stress sensitivity (subjective)
Induction of cognitive, physical, and social stress using Maastricht Acute Stress Test. Participant rate how much stress, discomfort, and pain they feel on a 10-cm visual analogue scale, with higher values indicating greater stress, discomfort, and pain. This is done prior to stress induction, in the middle, and at the end.
Time frame: 1 year
Cortisol awakening response
Measuring chronic stress by quantifying cortisol in morning samples (5 samples taken form the moment of waking every 15 minutes for 1 hour)
Time frame: 1 year
Fear
Exploring fear-related processes (conditioning, extinction, recall, and renewal) by means of a computerised task. Fear response is measured using skin conductance.
Time frame: 1 year
Fear (subjective)
Exploring fear-related processes (conditioning, extinction, recall, and renewal) by means of a computerised task. Fear response is measured subjective reports.
Time frame: 1 year
Attentional bias to emotional stimuli
Use of a dot-probe task to task attentional bias and change in attentional bias following SCFA vs. placebo supplementation. This is done via a computerised task, where reaction times are quantified.
Time frame: 1 year
Perceived Stress Scale (PSS)
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The Perceived Stress Scale (PSS) was devised by Cohen et al. (1983). It is a 14-item instrument designed to measure the degree to which situations in one's life are appraised as stressful. It provides a tool for examining issues about the role of appraised stress levels in the aetiology of disease and behavioural disorders. The scale is designed such that it asks the respondent to rate the frequency of his/her feelings and thoughts related to events and situations that occurred over a selected time-frame. Notably, high PSS scores have been correlated with higher biomarkers of stress, such as cortisol.
Time frame: 1 year
Positive and Negative Affect Schedule (PANAS)
The PANAS consists of two 10-item mood scales and was developed to provide brief measures of negative affect (NA) and positive affect (PA). NA and PA reflect dispositional dimensions, with high-NA epitomized by subjective distress and unpleasurable engagement, and low-NA by the absence of these feelings. By contrast, PA represents the extent to which an individual experiences pleasurable engagement with the environment. Respondents are asked to rate the extent to which they have experienced each particular emotion within a specified time period, on a 5-point scale. The scale points are: 1 'very slightly or not at all', 2 'a little', 3 'moderately', 4 'quite a bit', and 5 'very much'.
Time frame: 1 year
Depression, Anxiety, and Stress Scale (DASS-21)
The DASS is a set of three self-report scales designed to measure the negative emotional states of depression, anxiety and stress. Each of the three DASS scales contains 14 items, divided into subscales of 2-5 items with similar content. The Depression scale assesses dysphoria, hopelessness, devaluation of life, self-deprecation, lack of interest/involvement, anhedonia, and inertia. The Anxiety scale assesses autonomic arousal, skeletal muscle effects, situational anxiety, and subjective experience of anxious affect. The Stress scale is sensitive to levels of chronic non-specific arousal. Subjects are asked to use 4-point severity/frequency scales to rate the extent to which they have experienced each state over the past week. Scores for Depression, Anxiety and Stress are calculated by summing the scores for the relevant items. DASS21 will be used in the present study.
Time frame: 1 year
Gastointestinal symptom rating scale (GSRS)
The GSRS (Svellund et al., 1988) is a disease-specific instrument of 15 items combined into five symptom clusters depicting Reflux, Abdominal pain, Indigestion, Diarrhoea and Constipation. The GSRS has a seven-point graded Likert-type scale where 1 represents absence of troublesome symptoms and 7 represents very troublesome symptoms. The reliability and validity of the GSRS are well-documented, and norm values for a general population are available.
Time frame: 1 year
Microbiota composition
Analysis of microbiota composition at baseline and after SCFA mixture administration in faecal samples
Time frame: 1 year
Circulating SCFA
Measurement of SCFA concentration in blood samples
Time frame: 1 year