This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie Grant Agreement No. 956851.

Biosketch Kristin Verbeke, Pharm, PhD ​

Kristin Verbeke graduated from the KU Leuven, Belgium as a pharmacist in 1991. She obtained a PhD in Pharmaceutical Sciences at the Laboratory of Radiopharmaceutical Chemistry in 1995 and subsequently spend a postdoctoral period in developing radioactively labelled compounds. In 2002, she was appointed at the department of gastroenterology of the Medical Faculty of the Leuven University where she got involved in the use of stable isotope labelled compounds to evaluate gastrointestinal functions. Within the University Hospitals Leuven, she is responsible for the clinical application of diagnostic 13C- and H2-breath tests.

Her current research interest specifically addresses the microbial bacterial metabolism in the human colon. Her team has developed several analytical techniques based on mass spectrometry and stable isotope or radioisotope technologies to evaluate several aspects of intestinal metabolism and function in humans (transit time, intestinal permeability, carbohydrate fermentation, protein fermentation, metabolome analysis). Collaborative research has allowed showing an aberrant bacterial metabolism in patient groups with end stage renal failure, inflammatory bowel diseases, irritable bowel disorders and alcohol abuse. These collaborations all have resulted in high quality peer-reviewed papers. In addition, she showed the impact of dietary interventions (modulation of macronutrient composition, pre- or probiotic interventions) on the microbial metabolism and its impact on health.

As a PI, she acquired grant support from the university and different funding bodies and successfully completed these projects. Similarly, she supervised several PhD projects that all resulted in the achievement of a PhD degree. Her research resulted in over 180 full research papers.

Together with colleague Prof. J. Delcour, she was beneficiary of the W.K. Kellogg Chair in Cereal Sciences and Nutrition (2010-2020). She is the president of the Belgian Nutrition Society, the vice-chair of the Leuven Food Science and Nutrition Center and the co-chair of the Prebiotic task force at ILSI Europe. Furthermore, Kristin Verbeke is the editor of the journal Gut Microbiome and member of the editorial board of Gastrointestinal Disorders.

Abstract

Delivery of short chain fatty acids into the human colon to evaluate their impact on the host

Short chain fatty acids (SCFA) are the main metabolites from bacterial fermentation of dietary fibre in the large intestine. After production in the colon, they are rapidly absorbed by the colonocytes, partially oxidised in the colonic cells, transported and metabolised in the liver after which the remaining fraction ends up in the systemic circulation. Systemic SCFA are often proposed as mediators of the systemic health benefits associated with fibre consumption. However, most of the information about the effects of SCFA on health is derived from in vitro and animal experiments and very little is known in humans.
To further elucidate the role of SCFA for human health, we designed a series of experiments to (i) quantify the fraction of colonic SCFA that reached the systemic circulation, (ii) evaluate the effect of different dietary fibres on systemic SCFA concentrations and (iii) evaluate the impact of colonic administered SCFA on the stress response in healthy subjects.

Those experiments required the administration of a known amount of SCFA directly in the colon of healthy subjects. Therefore, we developed colon delivery capsules that contained the SCFA sodium salts together with citric acid to keep the pH below pH 6.0 and that were coated with a pH-dependent coating (Eudragit S). Using these capsules in combination with stable isotope technology, we were able to determine that 36%, 9% and 2% of colonic administered acetate, propionate and butyrate, respectively, reached the systemic circulation. Furthermore, the amount of SCFA in the circulation significantly differed depending on the fermentability of administered fibre. Finally, moderate and high doses of colonic delivered SCFA significantly reduced the cortisol response to an acute experimental stressor in healthy male participants.
In conclusion, colon delivery capsules are an efficient tool to deliver compounds to the colon and dissect their impact and mechanisms of action on human health.