Short-Chain Fatty Acids in Lypopolysaccharide-Induced Inflammation and Executive Function

NCT07713641 | Recruiting

• 1 other identifier: S69844
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Endotoxemia; Inflammation; Executive Function (Cognition)

Keywords

scfa; short-chain fatty acids; butyrate; proprionate; acetate; lypopolysaccharide; lps; endotoxemia; lps challenge; experimental; inflammation; experimental inflammation; experimental endotoxemia; systemic inflammation; gut-brain axis; microbiota; microbiota-gut-brain axis; executive function; working memory; inhibition; cognitive inhibition; response inhibition; cognitive flexibility; task switching; healthy volunteers; sickness behaviour

Outcome Measures

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.

  2 hours before LPS injection, and at 0, 1, 2, 3, 4, 5, and 6 hours after LPS injection

Secondary Outcomes (14)

• Serum pro- and anti-inflammatory cytokine response to the LPS challenge

  2 hours before LPS injection, and at 0, 1, 2, 3, 4, 5, and 6 hours after LPS injection

• High-sensitivity C-reactive protein (hs-CRP) response to the LPS challenge

  2 hours before LPS injection, and at 2, 6, and 24 hours after LPS injection

• LPS-induced sickness behaviour (SicknessQ)

  2 hours before LPS injection, and at 0, 1, 2, 3, 4, 5, and 6 hours after LPS injection

• Body temperature response to the LPS challenge

  2 hours before LPS injection, and at 0, 1, 2, 3, 4, 5, and 6 hours after LPS injection

• Heart rate response to LPS challenge

  2 hours before LPS injection, and at 0, 1, 2, 3, 4, 5, and 6 hours after LPS injection

Other Outcomes (10)

• Baseline gut microbiota composition

  Single fecal sample collected within the 3 days prior to the test day

• Mood - valence (MDMQ)

  2 hours before LPS injection, and at 0, 1, 2, 3, 4, 5, 6 and 24 hours after LPS injection

• Mood - alertness (MDMQ)

  2 hours before LPS injection, and at 0, 1, 2, 3, 4, 5, 6 and 24 hours after LPS injection

Study Arms (2)

SCFA Colon-Delivery Capsules

EXPERIMENTAL

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.

Dietary Supplement: Short-Chain Fatty Acid Colon-Delivery Capsules; Biological: Lipopolysaccharide (LPS)

Placebo

PLACEBO COMPARATOR

Single acute oral dose of placebo capsules containing microcrystalline cellulose and matching excipients, matched in appearance and number to the SCFA capsules.

Dietary Supplement: Placebo capsules; Biological: Lipopolysaccharide (LPS)

Interventions

Placebo capsules DIETARY_SUPPLEMENT

Single 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.

Also known as: Placebo, microcrystalline cellulose

Placebo

Short-Chain Fatty Acid Colon-Delivery Capsules DIETARY_SUPPLEMENT

Single 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.

SCFA Colon-Delivery Capsules

Lipopolysaccharide (LPS) BIOLOGICAL

Single 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.

Also known as: LPS, Endotoxin

Placebo; SCFA Colon-Delivery Capsules

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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
• Proficiency in English and/or Dutch

You may not qualify if:

• 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)
• History of immune system disorder, including inflammatory, autoimmune, or severe allergic conditions (e.g., rheumatoid arthritis, lupus, celiac disease, or severe allergies such as anaphylaxis)
• History of neuropsychiatric disorder (e.g., ADHD, autism spectrum disorder, learning disorder, Tourette's syndrome)
• History of major head trauma (e.g., concussion with loss of consciousness or long-term symptoms)
• History of severe infection (e.g., sepsis, pneumonia requiring hospitalization, meningitis, endocarditis, or other systemic infection requiring hospitalization, intravenous antibiotics, or intensive care)
• One or more diagnoses based on the Mini International Neuropsychiatric Interview (MINI)
• One or more diagnoses based on ROME-IV criteria for gastrointestinal disorders
• Any disorder that, in the investigator's opinion, might jeopardise the participant's safety or compliance with the protocol
• Any prior or concomitant treatment that might jeopardise the participant's safety or compromise the integrity of the study
• Participation in an interventional trial with an investigational medicinal product (IMP) or device
• Current or recent (past month) prescribed medication use, with particular attention to cardiovascular drugs, steroids, NSAIDs, and centrally-acting drugs (excluding isolated over-the-counter use such as ibuprofen or paracetamol, and hormonal contraceptives in women)
• Use of psychotropic medication within the past year (e.g., antidepressants, anxiolytics, antipsychotics)

Sponsors & Collaborators

• Universitaire Ziekenhuizen KU Leuven: lead
• University Hospital, Essen: collaborator
• Flemish institute of biotechnology (VIB): collaborator

Study Sites (1)

University Hospital Leuven (UZ Leuven)

Leuven, 3000, Belgium

RECRUITING

MeSH Terms

Conditions

Endotoxemia; Inflammation; Van der Woude syndrome; Inhibition, Psychological

Interventions

microcrystalline cellulose; Lipopolysaccharides; Endotoxins

Condition Hierarchy (Ancestors)

Bacteremia; Sepsis; Infections; Toxemia; Systemic Inflammatory Response Syndrome; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Glycoconjugates; Carbohydrates; Polysaccharides, Bacterial; Polysaccharides; Lipids; Antigens, Bacterial; Antigens; Biological Factors; Bacterial Toxins; Toxins, Biological

Study Officials

• Lukas Van Oudenhove, MD, PhD

  Laboratory for Brain-Gut Axis Studies, Translational Research Center for Gastrointestinal Disorders, Department of Chronic Diseases and Metabolism, KU Leuven, 3000 Leuven, Belgium

  PRINCIPAL INVESTIGATOR

• Kristin Verbeke, PhD

  Translational Research Center for Gastrointestinal Disorders, Department of Chronic Diseases and Metabolism, KU Leuven, 3000 Leuven, Belgium

  PRINCIPAL INVESTIGATOR

• Boushra Dalile, PhD

  Laboratory for Brain-Gut Axis Studies, Translational Research Center for Gastrointestinal Disorders, Department of Chronic Diseases and Metabolism, KU Leuven, 3000 Leuven, Belgium

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Franco Ruiz, M.D.

CONTACT

+32456716114; franco.ruiz@kuleuven.be

Dina Satriawan, M.D., Mnsci(Adv)

CONTACT

+32 16 71 03 66; dina.satriawan@kuleuven.be

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Two-arm parallel-group design comparing SCFA colon-delivery capsules versus placebo. A single intravenous bolus of lipopolysaccharide (0.4 ng/kg body weight) is administered to all participants as a fixed inflammatory challenge condition.

Study Record Dates

• First Submitted: June 30, 2026
• First Posted: July 20, 2026
• Study Start: October 24, 2025
• Primary Completion (Estimated): March 30, 2027
• Study Completion (Estimated): March 30, 2027
• Last Updated: July 20, 2026

Record last verified: 2026-06

Locations

BE (1)