Studies on non-digestible carbohydrates in the human intestine : Focus on kinetics of fermentation and degradation

Samenvatting

Increased consumption of non-digestible carbohydrates (NDCs), or dietary fiber, has been linked to numerous health benefits such as a reduced risk of obesity or improved intestinal function. Certain NDCs can be fermented by intestinal microbiota. Fermentation can result in microbiota composition changes. Because the composition of the intestinal microbiota in the small and large intestine as well as bacterial metabolites likely play an important role in health, modulating the microbiota through changes in diet can be a strategy to improve health status. Fermentable prebiotics, including galacto-oligosaccharides (GOS), fructo-oligosaccharides (FOS), and inulin, can selectively stimulate the growth and/or activity of specific intestinal bacteria. Moreover, fermentation results in metabolite production, mainly short-chain fatty acids (SCFA). It has been shown that increased uptake of SCFAs from the large intestine is associated with improvements in metabolic health markers in the blood. Detailed knowledge on NDC degradation and consequent metabolite production and microbiota shifts in the human intestine is lacking. This information will facilitate the prediction of potential beneficial health consequences of NDC consumption.

The work in this thesis describes the kinetics of fermentation and degradation of NDCs, mainly in the human small intestine. Several models to study digestion and fermentation were applied, namely in vitro batch fermentation models as well as intervention trials in human subjects with the use of naso-intestinal catheters and stable isotopes. The effects of acute short- and longer-term effects of varying NDC types and concentrations on the intestinal microbiota and metabolites were investigated, in relation to metabolism. In the Netherlands, bread and grain products are the main sources of NDCs. The effects of whole-grain wheat products or refined wheat products on the composition and functions of the fecal microbiota in adults was investigated. We also address challenges to consider when studying the human gastrointestinal tract. Most commonly, the effects of NDCs on the intestinal environment in humans are studied through analysis of feces. Feces is easy to collect, but might not be directly representative of the intestinal content. Additional methods are therefore needed to sample more locally to better understand the effects of dietary interventions inside the intestine. In this thesis, practical and technical aspects of using intestinal catheters in human subjects for delivery and sampling from the jejunum, ileum, and colon are provided. Given the burden of this method for subjects, alternative methods to study the inner world of digestion and fermentation are warranted. Access to the human intestinal lumen will be possible in the future through minimally-invasive, novel gastrointestinal sampling capsules. An analytical toolbox with novel methodology is described to stabilize and analyze the resulting intestinal samples, which can be used in combination with gastrointestinal sampling capsules.

Little is known about the direct interaction between NDCs and the human small intestine. We show that in vitro the small intestine microbiota degraded some NDCs. The fermentation and degradation rate depended on the type and size of the NDC. Importantly, the effects on the microbiota and metabolites profiles were strongly dependent on the subject's initial microbiota composition. This supports the importance of a personalized nutritional approach through the intestinal microbiota to improve health. Two clinical feasibility trials were executed to study acute fermentation kinetics of a FOS:GOS mix in the human intestine. GOS and FOS each have a unique structure and both contain molecules of different sizes and linkages. The degradation of all carbohydrate compounds present in FOS and GOS mixtures in the human intestine were analyzed using advanced chemical analyses. We provide direct evidence on resistances of various compounds to digestion in the small intestine can be used for further development of prebiotics that completely resist digestion in the human small intestine. The development and application of NDCs in foods as sugar replacers is of interest to decrease the caloric value of food, may lower blood glucose levels after eating, and can have a beneficial effect on the intestine. Furthermore, SCFAs were also delivered directly into the human intestine to investigate their role in glucose and lipid metabolism. Acetate, propionate, and butyrate contained a 13C label, which could be traced in various molecules. The results showed that SCFAs were vividly taken up from the intestine and converted by the host. This highlights the close link between the microbiota and host metabolism.