Glycan Competition in a Bioreactor Setting Shapes the Gut Microbiota in Periods of Stress
The human gut microbiota relies on complex carbohydrates (glycans) for energy and growth, primarily dietary fiber and host-derived mucins. We introduce a mathematical model of a glycan generalist and a mucin specialist in a two-compartment chemostat model of the human colon. Our objective is to characterize the influence of dietary fiber and mucin supply on the abundance of mucin-degrading species within the gut ecosystem. The integrity of the colonic mucus barrier is essential for overall human health and well-being, with the mucin specialist Akkermanisa muciniphila being associated with a healthy mucus layer. Competition may lead to mucus layer erosion, especially during periods of dietary fiber deprivation. Our model treats the colon as a gut reactor system, dividing it into two compartments that represent the lumen and the mucus of the gut, resulting in a complex system of ordinary differential equations with a large and uncertain parameter space. To understand the influence of model parameters on long-term behavior, we employ a random forest classifier, a supervised machine learning method. Additionally, a variance-based sensitivity analysis is utilized to determine the sensitivity of steady-state values to changes in model parameter inputs. By constructing this model, we can investigate the underlying mechanisms that control gut microbiota composition and function, free from confounding factors.
Bio: Thulasi Jegatheesan recently completed her PhD in Biophysics at the University of Guelph under the supervision of Dr. Hermann Eberl. The focus of her PhD research was the mathematical modelling of the human colon and the complex community of gut microbiota inhabiting the colon, particularly during periods of perturbation and gut dysbiosis.