A Mathematical Model to Facilitate Study of Hydrogen Cross-feeding by the Human Colonic Microbiota (P13-036-19)

Objectives The role of hydrogen cross-feeding microbes in digestive function is unclear, but several such organisms have been implicated in functional gastrointestinal disorders. In order to study the dynamics of hydrogen cross-feeders, we require a computational model that provides realistic predictions of food metabolism and metabolite cross-feeding by the human intestinal microbiota. The goal is to produce a model that captures the relationships between the concentrations of all major metabolites in the colon and the microbial population. Methods We adapted the existing model microPop [Kettle et al., Methods in Ecology and Evolution, 9, 399–409, (2017)] to the human colonic environment. The model divides the microbiota into functional groups, determined by the metabolites that they feed upon and produce. We introduced alterations to the bacterial functional groups in the original model, including the addition of sulphate-reducing bacteria (SRB), which have an important role in hydrogen cross-feeding. Further adaptions included running the model through three sequentially connected compartments representing the proximal, transverse and distal colon. To enhance the applicability of the model to the colon, the production of sulphated colonic mucins by the host was included. Results The model predicts comparable conditions to those found in experimental work. The sulphated mucins were degraded by saccharolytic members of the microbiota to smaller molecules, including hydrogen, short-chain sugars and free sulphate. These metabolites formed a food source for hydrogen cross-feeders, including SRB, as has been seen in rodent models. Cross-feeding for sulphate released from mucins may be more significant in the metabolism of SRB than dietary sulphate. Conclusions The model may be used to make predictions about the consequences of certain diets on the production of microbial-derived metabolites and the composition of the microbiota. It also provides predictions about the availability of nutrients in the colon to the host. Finally, the model allows us to perform theoretical studies on the role of hydrogen cross-feeders and the metabolites they secrete in digestive function. Funding Sources This work was funded by the Riddet Institute, a New Zealand Centre of Research Excellence.