Fate of Alkylresorcinols in the gastrointestinal tract of humans

The fate of alkylresorcinols in the human gastrointestinal tract: bioavailability, microbial metabolism and bioactivity

Cereals represent a major portion of our daily diet and are considered as a main source of energy. They contain numerous nutritional components like carbohydrates, fats, proteins, minerals, and phenolics. Cereal bran is also rich in fiber and phytochemicals, and they are mainly located in the outer layers of the grains. Bran contains phenolic compounds like alkylresorcinols (ARs) which are known to possess a range of biological activities including antioxidant activity and lowering the baseline cholesterol level. These are a class of amphiphilic 1,3-dihydroxy- 5-alkyl phenolic lipids, present mainly in rye and wheat bran and are proposed as biomarkers of whole grain diet. ARs having alkyl chains in the range of C15 to C25 (only odd numbered) are particularly abundant in wheat and rye bran and in food products containing these parts.

Aim
ARs may contribute to the health effects of wheat or rye bran diet as they have been reported to have antioxidant, anti-neoplastic and cholesterol lowering effects in the human body. However, the mechanism of ARs absorption through intestine and microbial metabolism in human body is not known. So, the main aim of this research is to clarify some of the aspects relative to the fate of ARs in the human body including bioaccessibility, absorption mechanism, microbial metabolism in the small and large intestine and anti-inflammatory activity.

Approach
Rye bran will be used as a starting material and processed in several ways to check the effect on bioaccessibility and behavior during digestion by using the in vitro harmonized INFOGEST protocol. Intestinal organoids (IOs) will be developed to assess ARs absorption and the exact mechanism of absorption. In vitro batch fermentation will be employed to study the microbial metabolism of ARs in the small and the large intestine, using ileum effluents and fecal sample as inoculum respectively. ARs microbial metabolites will be identified by HPLC-QTOF-MS. An acute intervention study will be carried out with human volunteers to further validate the findings of the in vitro studies and to characterize the pharmacokinetics of ARs in the human body. Lastly, ARs anti-inflammatory effect will be investigated using IOs combined with immune cells. Inflammation will be induced by using cytokines and then pro-inflammatory markers (IL-1β & IL-6) will be quantified using ELIZA kits.

This PhD project is a collaboration between the Food Quality and Design group and the Human Nutrition and Health chair group of Wageningen University and Research.