High-fat Diet (HFD) and Small Intestinal Microbiome

Overview

The investigators aim to characterize the upper small intestinal microbiome in healthy conditions in dependency on feeding condition (starved vs. high-fat-challenged) and diet (before and after 3 day high-fat-diet) Primary outcome will be the maximum culturable bacteria (aerobic and anaerobic) in small intestinal luminal content during acute liquid-fat challenge before vs. after a short-term (3 day) high-fat-diet In this pilot study, healthy volunteers will undergo i) an upper endoscopy for harvesting of small intestinal juice, mucosal biopsies and ii) blood withdrawal at baseline (starved) as well as during acute one-time high-fat luminal stimulation (within 3 hours after baseline) utilizing microbiological culture and 16S-RNA sequencing. The same procedure will be performed after 3 day high-fat-diet. During endoscopy an acute luminal high-fat challenge which will be repeated after a short-term (3 day) high-fat diet

Background: The small intestine represents the major site of lipid metabolism and absorption. Its microbiome has recently been demonstrated to regulate adaptive digestive and absorptive responses to dietary lipids in mice. The microbiome was thereby demonstrated to be a culprit to obesity development. In fact, high-fat diet (HFD) induced changes in the microbiome are most pronounced in the small intestine and transplantation of small bowel microbes from HFD conditions increased lipid absorption compared with low-fat-diet-derived microbes. In humans, HFD induced microbiota alterations has been demonstrated as dysbiosis in colonic and fecal flora9 but changes in the small intestinal microbiome before the onset of obesity have not been addressed so far. In HFD-associated obesity, an increased frequency of small intestinal bacterial overgrowth (SIBO)38 is observed in humans. SIBO so far has been defined as the presence of more than 105 CFU/ml of luminal aspirate or presence of colonic type bacteria determined by microbiological culture techniques5. Therefore, the current definition of SIBO has severe limitations. Specifically, this definition of SIBO is arbitrary, limited to luminal aspirate, aerobic bacteria and assessment in starved conditions. In clinical practice, SIBO is virtually never tested according to this definition. Therefore, it would be of great interest to investigate whether SIBO can be re-defined by investigating the dynamic behavior of the microbiota in the upper small intestine i) before (starved) and after HFD-stimulation and ii) by deep sequencing of 16S-RNA in luminal aspirate as well as biopsies (mucosa-associated compartment). The investigators will perform an observational case-control study in lean healthy volunteers applying an acute (one-time exposure) and short-term (3 day) HFD-challenge assessing duodenal juice and biopsies for quantity and quality of microbial consortia. This will help to define the acute response of the small intestinal microbiome to HFD and ultimately set the stage for a new definition of SIBO. Moreover, HFD is known to modulate a) the bile-acid-pool and b) gut-derived hormones such as incretins as well as c) thyroid-hormone-status. Thus, impact of acute (one-time exposure) and short-term (3 day) high-fat-stimulation on serum concentration and composition of bile-acids, incretins and thyroid-stimulating-hormone (TSH) plus peripheral thyroid hormones will be assessed.