The impact of intestinal health (also called gut health) on the development of a wide range of chronic disorders is commonly acknowledged. Gut health research is often focussed on the gut microbiota composition. Changes in a presence/absence of microbes inhabiting the colon under healthy conditions have been found to correlate with chronic diseases such as diabetes, Alzheimer’s’ disease, cardiovascular disease, cancer and many others. However, the causality between microbiota composition changes and chronic disease development remains to be resolved. Mechanistic insight into microbiota-induced health effects, though, is of crucial importance to find new treatments and ways to prevent chronic disease development strongly affecting the quality of life of the afflicted patient.
In relation to gut health, nutrition is a very important factor since it can either induce beneficial or adverse health effects, depending on the type of diet. A prudent diet, rich in fruits, vegetables, whole grains, legumes, nuts and fish has been shown to stimulate the growth of potentially beneficial microbes. Additionally, this diet has been reported to reduce inflammation and strengthen the intestinal barrier causing health-promoting effects. However, a Western-style diet rich in refined or processed foods, red meats, high concentrations of sweets, eggs, and butter, has been shown to induce opposite effects. Importantly, although the diet-induced effects start in the gut, they often induce systemic effect at other sides of the body. We believe that not necessarily the changes in the microbiota, but rather the alterations in the metabolites produces by these microbes play a crucial role in this process. Through a combination of in vivo and in vitro studies, we aim to establish, 1) which microbiota-derived bioactive compounds are induced by specific nutrients/diets, 2) which microbiota species are responsible for this synthesis and 3) via which underlying mechanisms do the compounds affect intestinal health.
Do bile acids play a causal role in Inflammatory Bowel Disease development?
Inflammatory bowel diseases (IBD) are devastating chronic diseases characterized by flare-ups alternating with periods of remission. The exact cause of IBD and the trigger inducing the flare-ups is still largely unknown. The PhD student Benthe van der Lugt (NWO/VLAG scholarship) explores the role of (sulphated) bile acids on the intestinal wall. For her project she makes use of sophisticated in vitro co-culture transwell models containing different types of intestinal cells (enterocytes and goblet cells) in combination with dendritic immune cells.
Fermentation of fatty acids by gut microbes: do they induce anti-inflammatory effects?
Human gut microbiota can metabolize fatty acids (FAs) resulting in the formation of conjugated , oxo- and hydroxy-FAs, all of which are reported to exert specific health effects. In his PhD project, Zongyao Huyan (CSC scholarship) 1) explores the possibility of modulating FAs metabolism by modifying food structure or composition and 2) investigates the functional effects of the identified FA metabolites on gut health. SHIME and in vitro co-culture transwell models are applied in the project in collaboration with the WUR Food Quality and Design group (Dr Edoardo Capuano and Dr Nicoletta Pellegrini).
Epigenetic imprinting in utero by microbial short chain fatty acids and the influence on early onset of type 1 diabetes
By far the most intensively studied microbiota-derived bioactive compounds are the Short Chain Fatty Acids (SCFAs). In the last decade, a pleiotropy of health effects have been attributed to SCFA. Interestingly, SCFAs are also known to induce epigenetic effects. The project of PhD student Aisha Leeflang (VLAG scholarship) examines whether SCFAs fortification of the maternal diet induces a protective effect on the development of type-1 diabetes. She will examine epigenetic programming effects in utero or during early life (the first 1000 days). This project is a collaboration with the WUR Host Microbe interaction group (Prof Dr Jerry Wells and Prof Dr Michiel Kleerebezem).
Functional consequences of diet-induced microbiota changes
explores the functional consequences of diet-induced effects on the microbiota composition. 16S rRNA sequencing has been applied on faecal samples isolated in different intervention studies. By applying different bioinformatic approaches, the functional effects induced by the different diets will be explored in this post-doc project (Polish National Agency for Academic Exchange- scholarship). These data will be linked to metabolites measured in the same faecal samples as well as a wide range of physiological parameters measured in the hosts.
Signalling from the gut to the brain: can mental health be improved by nutrients?
Apart from exploring nutrition-induced effects on intestinal health, my research also focusses on the gut-brain axis. In ongoing research I study the effects of nutrition and other environmental factors on brain-related disorders like Alzheimer’s’ disease. This research is aimed at clarifying how specific nutrients and other life-style factors can subsidize to the prevention or delay of cognitive decline. This topic will be examined in the MOCIA project (Maintaining Optimal Cognitive function in Aging, NWO cross-over) where we collaborate with the Donders Institute (Dr Esther Aarts, Dr Joukje Oosterman), WUR-FBR (Dr Jurriaan Mes) and other partners from the MOCIA consortium. In the SmartAge project (Horizon 2020-MSCA-ITN-2019) we will examine the effects of a dietary intervention on gut health in relation to cognitive decline in aging subjects in collaboration with Prof Dr Lisette de Groot.