A mathematical model to investigate the key drivers of the biogeography of the colon microbiota.

ABSTRACT

The gut microbiota, mainly located in the colon, is engaged in a complex dialogue with the large intestinal epithelium through which important regulatory processes for the health and well-being of the host take place. Imbalances of the microbial populations, called dysbiosis, are related to several pathological status, emphasizing the importance of understanding the gut bacterial ecology. Among the ecological drivers of the microbiota, the spatial structure of the colon is of special interest spatio-temporal mechanisms can lead to the constitution of spatial interactions among the bacterial populations and of environmental niches that impact the overall colonization of the colon. In the present study, we introduce a mathematical model of the colon microbiota in its fluid environment, based on the explicit coupling of a population dynamics model of microbial populations involved in fibre degradation with a fluid dynamics model of the luminal content. This modeling framework is used to study the main drivers of the spatial structure of the microbiota, specially focusing on the dietary fibre inflow, the epithelial motility, the microbial active swimming and viscosity gradients in the digestive track. We found 1) that the viscosity gradients allow the creation of favorable niches in the vicinity of the mucus layer; 2) that very low microbial active swimming in the radial direction is enough to promote bacterial growth, which sheds a new light on microbial motility in the colon and 3) that dietary fibres are the main driver of the spatial structure of the microbiota in the distal bowel whereas epithelial motility is preponderant for the colonization of the proximal colon; in the transverse colon, fibre levels and chemotaxis have the strongest impact on the distribution of the microbial communities.