Short-Chain Fatty Acids in Lypopolysaccharide-Induced Inflammation and Executive Function
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18-45
SponsorUniversitaire Ziekenhuizen KU Leuven
About this trial
Short-chain fatty acids (SCFAs) are substances produced by gut bacteria when they ferment dietary fiber. They can act as signals between the gut and the brain and may help regulate the body's immune and stress responses. Earlier work has shown that delivering SCFAs to the colon can lower the stress hormone response to a mental stress task in healthy people, and laboratory studies suggest SCFAs can reduce inflammation. However, it is not yet known whether SCFAs can reduce inflammation in humans, or whether doing so protects mental performance.
This study uses a controlled, acute, and short-lasting challenge. Healthy adults receive a single, low dose of a bacterial substance called lipopolysaccharide (LPS) through a vein. LPS briefly activates the immune system and causes mild, flu-like symptoms (such as fatigue, headache, and feeling unwell) that pass on their own within a few hours. It does not cause a real infection.
Participants are randomly assigned to take either SCFA capsules or inactive placebo capsules on the morning of the test day, before the LPS challenge. Neither the participants, the researchers running the visit, nor the researchers analyzing the results know who received which capsules until the study is complete (triple-blind).
The main goal of the study is to test whether SCFAs, compared with placebo, reduce the inflammatory response to LPS, measured by markers of inflammation in the blood. The study also examines whether SCFAs reduce the associated sickness symptoms and whether they protect performance on tasks that measure core executive functions: the ability to keep relevant information in mind (working memory), the ability to hold back automatic responses or thoughts (inhibition), and the ability to switch flexibly between tasks or rules (cognitive flexibility). Blood, saliva, and stool samples are collected to measure inflammation markers, SCFA levels, stress hormones, and gut bacteria.
Participants attend a screening visit, a test day with monitoring for several hours, and a short follow-up visit the next day.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
Voluntary written informed consent obtained prior to any study procedure
Healthy, with no gastrointestinal or psychological complaints
Age 18-45 years
BMI 18.5-27 kg/m2
Disqualifiers
History of previous or current neurological disorder (e.g., epilepsy, multiple sclerosis, migraine with aura)
History of previous or current psychiatric disorder (e.g., depression, anxiety disorders, bipolar disorder, schizophrenia)
History of previous or current gastrointestinal disorder (e.g., Crohn's disease, ulcerative colitis, irritable bowel syndrome)
History of previous or current endocrine disorder (e.g., diabetes, thyroid disorders, polycystic ovary syndrome)
Trial design
Design model
Parallel
Treatments tested in this trial
Short-Chain Fatty Acid Colon-Delivery Capsules
Dietary supplementSingle acute oral dose of pH-dependent colon-delivery capsules delivering a short-chain fatty acid mixture to the colon. The mixture comprises sodium acetate,sodium butyrate, and sodium propionate (54.4%, 21.2%, and 24.4% by weight), providing approximately 186 mmol total SCFA per dose (111 mmol acetate, 32 mmol butyrate, 43 mmol propionate). Capsules are sub-coated with hydroxypropylcellulose and coated with a pH-dependent layer (Eudragit FS 30 D with PlasACRYL T20). Taken on the morning of the test day with a standardized low-fiber breakfast.
Placebo capsules
Dietary supplementSingle acute oral dose of placebo capsules containing microcrystalline cellulose and matching excipients, an inert non-fermentable substrate. Matched in appearance and number to the SCFA capsules and taken on the morning of the test day with a standardized low-fiber breakfast.
Lipopolysaccharide (LPS)
Biological/VaccineSingle intravenous bolus of purified Escherichia coli-derived lipopolysaccharide (0.4 ng/kg body weight), administered one hour after capsule intake to all participants as a standardized experimental inflammatory challenge common to both study arms.
Treatment groups
56 Participants
are divided into 2 treatment groupsGroup A: SCFA Colon-Delivery CapsulesExperimental treatment 2 interventions
Group B: PlaceboPlacebo comparator 2 interventions
Trial outcomes
Primary outcomes
1
Serum interleukin-6 (IL-6) response to the LPS challenge
Effect of SCFA versus placebo on the systemic inflammatory response to experimental endotoxemia, indexed by serum IL-6 concentrations measured at serial timepoints across the test day following the intravenous LPS bolus. The primary analysis evaluates the treatment-by-timepoint interaction on the IL-6 time course using a linear mixed model, with treatment (SCFA vs. placebo) as a between-subject factor and timepoint as a within-subject factor.
Time frame
2 hours before LPS injection, and at 0, 1, 2, 3, 4, 5, and 6 hours after LPS injectionSecondary outcomes
1
Serum pro- and anti-inflammatory cytokine response to the LPS challenge
Effect of SCFA versus placebo on serum concentrations of TNF-alpha, IL-1-beta, IFN-gamma, IL-8, IL-4, and IL-10. Analyzed as treatment-by-timepoint interactions using linear mixed models.
Time frame
2 hours before LPS injection, and at 0, 1, 2, 3, 4, 5, and 6 hours after LPS injection2
High-sensitivity C-reactive protein (hs-CRP) response to the LPS challenge
Effect of SCFA versus placebo on serum high-sensitivity C-reactive protein (hs-CRP) concentrations, measured at selected timepoints on the test day and at the 24-hour follow-up visit.
Time frame
2 hours before LPS injection, and at 2, 6, and 24 hours after LPS injection3
LPS-induced sickness behaviour (SicknessQ)
Effect of SCFA versus placebo on subjective sickness behaviour, assessed with the Sickness Questionnaire (SicknessQ), analyzed across timepoints on the test day.
Time frame
2 hours before LPS injection, and at 0, 1, 2, 3, 4, 5, and 6 hours after LPS injection4
Body temperature response to the LPS challenge
Effect of SCFA versus placebo on body temperature (degrees Celsius).
Time frame
2 hours before LPS injection, and at 0, 1, 2, 3, 4, 5, and 6 hours after LPS injectionOther outcomes
1
Baseline gut microbiota composition
Baseline fecal gut microbiota composition, characterized by quantitative microbiome profiling from a single fecal sample collected before the test day. Examined in exploratory analyses as a baseline predictor of inter-individual variability in systemic SCFA uptake and treatment response.
Time frame
Single fecal sample collected within the 3 days prior to the test day2
Mood - valence (MDMQ)
Effect of SCFA versus placebo on self-reported mood valence (good-bad dimension), assessed with the Multidimensional Mood Questionnaire (MDMQ/MDBF). Score range 1-40; higher scores indicate a more positive mood.
Time frame
2 hours before LPS injection, and at 0, 1, 2, 3, 4, 5, 6 and 24 hours after LPS injection3
Mood - alertness (MDMQ)
Effect of SCFA versus placebo on self-reported alertness (awake-tired dimension), assessed with the Multidimensional Mood Questionnaire (MDMQ/MDBF). Score range 1-40; higher scores indicate greater alertness.
Time frame
2 hours before LPS injection, and at 0, 1, 2, 3, 4, 5, 6 and 24 hours after LPS injection4
Mood - calmness (MDMQ)
Effect of SCFA versus placebo on self-reported calmness (calm-restless dimension), assessed with the Multidimensional Mood Questionnaire (MDMQ/MDBF). Score range 1-40; higher scores indicate greater calmness.
Time frame
2 hours before LPS injection, and at 0, 1, 2, 3, 4, 5, 6 and 24 hours after LPS injectionSponsors and contacts
Click on the lead sponsor to view all of their trials.
Universitaire Ziekenhuizen KU Leuven
Lead sponsor
University Hospital, Essen
Collaborator
Flemish institute of biotechnology (VIB)
Collaborator
Source ClinicalTrials.gov