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.
Inclusion Criteria:
Exclusion Criteria:
franco.ruiz@kuleuven.be+32456716114
Triple-blind design. Participants, study personnel administering the intervention and interacting with participants, outcome assessors, and the personnel performing the data analysis are all blinded to treatment allocation. Randomization and capsule allocation are performed by a collaborator not otherwise involved in the study. Capsules are labelled with a randomization number and kept in a non-transparent recipient. Blinding is maintained until database lock and completion of the primary analysis.
A single acute oral dose of colon-delivery capsules delivering a short-chain fatty acid mixture (approximately 186 mmol total SCFA: 111 mmol acetate, 43 mmol propionate, 32 mmol butyrate; molar ratio approximately 60:23:17), taken on the morning of the test day with a standardized low-fiber breakfast.
Single acute oral dose of placebo capsules containing microcrystalline cellulose and matching excipients, matched in appearance and number to the SCFA capsules.
dina.satriawan@kuleuven.be+32 16 71 03 66
The Effects of Short-Chain Fatty Acids in Psychosocial Stress-Induced Impairment on Core Executive Functions
The Role of Short Chain Fatty Acids in Microbiota-gut-brain Axis
Endotoxin-induced Inflammatory and Behavioral Responses and Predictors of Individual Differences
Brain Responses to Short-Chain Fatty Acid Intervention
Brain Biomarker on Inflammation Response
Safety and Feasibility of an Endotoxemia Model
Individual Differences in Acute Response to Experimental Inflammation: Microcirculatory Changes and Psychological Predictors
Concentration/Meditation Limits Inflammation