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

Overview

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.