Multi-scale modelling of transport in the gastrointestinal tract – TransportGut

The gastrointestinal tract involves many biological, chemical and physical phenomena to secure the absorption of nutrients from our food. Also, specific sites of the digestive mucosa are gateways to our immunologic system which pave the way for the development of innovative oral therapeutic strategies. These strategies are based on the encapsulation of drugs in nano- or micro- particles or the administration of bacteria, which would target these sites in order to induce an immune response. However, a major scientific barrier is to be able to predict the flow of these "micro-particles" and thus control the dose absorbed by our body.

The objective of TransportGut is to develop a predictive and comprehensive modelling of the transport of microparticles in the gastrointestinal system.

The challenge of such a model is to account for the different specificities of the physical environment of the digestive tract on the phenomena of transport and mixing. On the one hand, transport and mixing are controlled by the mechanical activity of the smooth muscles of the intestinal mucosa, on both macroscopic and microscopic scales. On the other hand, this activity varies according to the time scales considered. Several scales are thus relevant: the microstructures of the mucosa, the isolated organ and along the digestive system. Mixing at large scales are probably controlled by mixing at small scales. There is currently no particle transport model that takes into account these different scales.

TransportGut is an integrated and interdisciplinary project that draws on the complementary expertise of three teams in biorheology, theoretical biophysics and physiology. The team of the Laboratoire Rhéologie et Procédés (LRP) has significant experience in the development of experiments in complex fluid mechanics at macroscopic and microscopic scales, as well as in numerical modeling of flows in the gastrointestinal tract. The team of the Laboratoire Jean Perrin (LJP) has expertise in theoretical modeling of the transport of bacteria and their interactions with the immune system of the digestive tract. Finally, the team from Techniques de l’Ingénierie Médicale et de la Complexité (TIMC-IMAG) develops experimental systems and original technologies for understanding the physiology of smooth muscles.

Based on experiments at the interface of physiology and fluid mechanics and numerical simulations of flows, we propose to develop an analytical model of transport connecting these different scales. We will develop experiments on animal models to study the transport of particles along the digestive system and in the vicinity of microstructures of the intestinal mucosa. These experiments will be used to simulate numerically the coupling between flows at microscopic and macroscopic scales in order to understand the role of active and microstructured interfaces on the transport and mixing of microparticles. All of these data from experiments and numerical simulations will make it possible to build analytical and simplified models of the transport and mixture of particles at different spatial and temporal scales. This model would predict the spatiotemporal dispersion of particles in order to be a decision-making tool for the pharmaceutical industry, but also to understand the fundamental mechanisms that govern the spatial structure of the intestinal microbiota.