Project

Non-invasive continuous gut microbial fermentation measurement for health and disease

The byproducts of fermentation of indigestible carbohydrates (like fiber) are considered beneficial for health, whereas the byproducts of protein fermentation are considered to be detrimental. In this project, we aim to develop a non-invasive real-time in vivo gut microbial fermentation chamber for mice by making use of gas sensors. The ability to measure gut microbial activity and produced byproducts allows us to analyse whether we can steer the production of beneficial fermentation products in the intestine, which will be linked to molecular elucidation of underlying mechanisms in the intestines.

Background

Evidence is accumulating that the gut microbiome is involved in the etiology of obesity and obesity-related complications such as non-alcoholic fatty liver disease, insulin resistance, and type 2 diabetes mellitus. The gut bacteria ferment indigestible carbohydrates (for example, dietary fiber) and non-digested proteins, thereby yielding metabolites and fermentation gasses like methane (CH4), hydrogen (H2), and hydrogen sulfide (H2S). Interestingly, the more distal colonic microbiota primarily ferments peptides and proteins, as the availability of fermentable fiber, the major and preferred energy source for the microbiota, is limited here. This is especially the case when a Western diet being low in fiber is consumed. This protein fermentation yields mainly harmful products which might be detrimental for the host gut and metabolic health. Therefore, a switch from protein to carbohydrate fermentation could be of major interest for the prevention and/or treatment of metabolic diseases.

Project description

We currently have an extended indirect calorimetry system for mice with additional gas sensors that measure carbohydrate fermentation. Here, we aim to extend this system further with a new sensor that can measure protein fermentation. The in vivo altered gut microbiota activity and fermentation due to different nutritional exposures will be observed with indirect calorimetry and causally linked to molecular analyses. One aim is to determine whether we can induce a shift from protein to carbohydrate fermentation. Further, we will study the effects of different nutritional exposures on the fermentation and oxidation kinetics in different metabolic health states (healthy, pre-diabetic obese, and obese) in a preclinical model, which will be paralleled by similar studies -in humans- performed at Maastricht University for the non-invasive parameters.