Healthy Fat, Happy Microbiome (TAPIR), Proof-of-Concept Study (TAPIR)

Rationale: The role of dietary lipids in host-microbiome research has for a long time been overlooked; as high lipid intake has been recently indicated to have the most pronounced effect on the small intestinal microbiome, fecal-oriented studies might have missed their important, local effect. Indications for an interaction between dietary lipids and the small intestinal microbiome are mainly based on animal studies, but human data are largely missing. This study therefore aims at exploring this principal in vivo in healthy individuals.

Primary objective: To assess the effect of dietary lipids on the small intestinal microbiome in humans (proof-of-concept), the primary objective of our study is to measure production of microbiota-derived lipid metabolites in the human small intestine after consumption of a plant-based high-fat shake in healthy pre-conditioned subjects.

Secondary objectives: To explore future perspectives for dietary lipid - small intestinal microbiome interactive research, the secondary objectives of our study are

1. To compare the levels of microbiota-derived lipid metabolites in aspirate samples obtained through a naso-intestinal catheter (golden standard; invasive sampling method) and an aspiration capsule (less invasive, innovative sampling method), and in blood (local versus systemic effect) and feces (small intestinal versus fecal effect; less invasive sampling);
2. To investigate the acute effect of a high-fat shake on the composition and transcriptome activity of the small intestine microbiota in aspirate samples of healthy pre-conditioned subjects; 2a) To compare the acute effects on the small intestine microbiota composition in aspirate samples obtained through a naso-intestinal catheter versus those obtained via an aspiration capsule;
3. To study and compare the effect of a 8-day plant-based mild ketogenic preconditioning diet on the composition of the small intestine microbiota (aspiration capsule) and the fecal microbiota.

Study design: Proof-of-concept intervention study

Study population: 16 healthy adults, BMI between 18.5-30 kg/m2.

Intervention: 8-days preconditioning mild ketogenic controlled diet followed by a high fat shake challenge with a naso-intestinal catheter.

Main study parameters/endpoints: The primary study parameters are the microbial-derived metabolites from linoleic acid and plant sterols after consumption of the high fat shake.

Secondary study parameters include microbiota composition and transcriptome activity. Other parameters include inflammatory markers and ex-vivo analyses.

Study Overview

• Status: Completed
• Conditions: Small Intestine
• Intervention / Treatment: Other: plant-based mild ketogenic controlled diet; Other: high-fat shake

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Mara van Trijp, PhD; Phone Number: + 31 (0) 317 48 67 39; Email: mara.vantrijp@wur.nl
• Study Contact Backup: Name: Lonneke Janssen Duijghuijsen, PhD; Email: lonneke.janssenduijghuijsen@wur.nl

Study Locations

• Netherlands
  • Gelderland
    • Wageningen, Gelderland, Netherlands, 6708WE
      • Wageningen University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Adult male or female
• BMI 18.5-30 kg/m2
• Suitable veins for insertion of cannula

Exclusion Criteria:

• Having a history of medical or surgical events that may either put the subject at risk because of participation in the study, or influence the results of the study, including diabetes mellitus, dyslipidemia, a swallowing disorder, gastrointestinal or liver disease, irritable bowel syndrome, sleeping apnea, renal failure, cancer, nose/throat diseases, gastric bypass surgery, use of anticoagulants; as determined by the medical supervisor;
• Having a bleeding/coagulation disorder, including hemophilia, Von Willebrand disease, Bernard-Soulier, Glanzmann thrombasthenia or thrombocytopenia;
• Use of antibiotics within 3 months of starting the study or planned during the study;
• Use of any medications in the previous week that could substantially alter gastrointestinal motor function (e.g., opioids, prokinetics, anticholinergics, laxatives), or acidity (PPI, H2RA), as determined by medical supervisor;
• Use of pro- and prebiotic supplements within 4 weeks of starting the study;
• Planning or scheduled to undergo magnetic resonance imaging (MRI) at any time during the course of the study (the SIMBA Capsule is MR unsafe)
• Currently following a very low carbohydrate (ketogenic) diet;
• Having regularly less than 3 bowel movements per week (being constipated);
• Alcohol consumption >21 glasses a week (women) or >28 glasses a week (men);
• Pregnant, lactating or wishing to become pregnant in the period of the study (self-reported);
• Not willing to give up blood donation during the study;
• Food allergies or intolerances for products that we use in the study;
• Current smokers;
• Current users of soft and/or hard drugs;
• Participation in another clinical trial at the same time;
• Being an employee of the Food, Health & Consumer Research group of Wageningen Food & Biobased Research or Human Nutrition and Health Department of Wageningen University.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 8-days plant-based preconditioning mild ketogenic controlled diet followed by a high-fat shake.

Other: plant-based mild ketogenic controlled diet; Plant-based mild ketogenic diet (10-20EN% carbohydrates, 10-20EN% protein, and 60-70EN% fat), consisting of a daily breakfast, lunch, dinner, and snacks.; Other: high-fat shake; The high-fat shake consists of unsweetened almond milk, sunflower oil, and plant sterols, resulting in a shake containing 885 kcal (1.5g protein, 97.3g fat, and 0.8g sugar).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
lipid metabolites from linoleic acid and plant sterols in the small intestine aspirates	Concentrations of microbiota-derived lipid metabolites in the small intestine aspirates, obtained by a naso-intestinal catheter, measured by lipidomics.	0-6 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
lipid metabolites in small intestine aspirate samples obtained with an aspiration capsule.	Concentrations of microbiota-derived lipid metabolites in the small intestine aspirates, obtained by an aspiration capsule, measured by lipidomics.	0-6 hours
small intestine microbiota composition	The relative composition (%) of the small intestine microbiota in aspirate samples obtained by an intestinal catheter.	0-6 hours
small intestine microbiome capacity	The functional capacity (transcriptomic activity) of the small intestine microbiota in aspirate samples obtained by an intestinal catheter.	0-6 hours
Faecal microbiota	The relative composition (%) of the faecal microbiota	Baseline, after 8 days.
Blood lipid metabolites	Lipid metabolites (HYA, CLA, all untargeted lipid metabolites) will be measured in blood samples with lipidomics.	0-6 hours
Blood triglycerides	Concentrations of triglycerides	0-6 hours
Blood free fatty acids	Concentrations of free fatty acids	0-6 hours
small intestine microbiota	The relative composition (%) of the small intestine microbiota in aspirates obtained by an aspiration capsule.	Baseline, after 5 days.
small intestine microbiome	The functional capacity (transcriptomic activity) of the small intestine microbiota in aspirates obtained by an aspiration capsule.	Baseline, after 5 days.

Other Outcome Measures

Outcome Measure	Time Frame
Blood LPS	0-6 hours
Blood ApoB48	0-6 hours

Collaborators and Investigators

• Sponsor: Wageningen University
• Collaborators: Wageningen University and Research

Study record dates

Study Major Dates

• Study Start (Actual): October 20, 2023
• Primary Completion (Actual): November 6, 2023
• Study Completion (Actual): December 22, 2023

Study Registration Dates

• First Submitted: September 12, 2023
• First Submitted That Met QC Criteria: September 28, 2023
• First Posted (Actual): October 3, 2023

Study Record Updates

• Last Update Posted (Actual): January 10, 2024
• Last Update Submitted That Met QC Criteria: January 9, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Microbiota; Microbial metabolites; Dietary fat
• Other Study ID Numbers: NL81345.081.23

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No