The human intestinal microbiota starts to form immediately after birth and is important for the health of the host. During the first days, facultatively anaerobic bacterial species generally dominate, such as Enterobacteriaceae. These are succeeded by strictly anaerobic species, particularly Bifidobacterium species. An early transition to Bifidobacterium species is associated with health benefits; for example, Bifidobacterium species repress growth of pathogenic competitors and modulate the immune response. Succession to Bifidobacterium is thought to be due to consumption of intracolonic oxygen present in newborns by facultative anaerobes, including Enterobacteriaceae. To study if oxygen depletion suffices for the transition to Bifidobacterium species, here we introduced a multiscale mathematical model that considers metabolism, spatial bacterial population dynamics, and cross-feeding. Using publicly available metabolic network data from the AGORA collection, the model simulates ab initio the competition of strictly and facultatively anaerobic species in a gut-like environment under the influence of lactose and oxygen. The model predicts that individual differences in intracolonic oxygen in newborn infants can explain the observed individual variation in succession to anaerobic species, in particular Bifidobacterium species. Bifidobacterium species became dominant in the model by their use of the bifid shunt, which allows Bifidobacterium to switch to suboptimal yield metabolism with fast growth at high lactose concentrations, as predicted here using flux balance analysis. The computational model thus allows us to test the internal plausibility of hypotheses for bacterial colonization and succession in the infant colon.

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FrieslandCampina, Amersfoort, The Netherlands
Centrum Wiskunde & Informatica, Amsterdam (CWI), The Netherlands

Versluis, D., Schoemaker, R., Looijesteijn, E., Muysken, D., Jeurink, P., Paques, M., … Merks, R. (2022). A multiscale spatiotemporal model including a switch from aerobic to anaerobic metabolism reproduces succession in the early infant gut microbiota. mSystems, 7(5), e00446‐22:1–e00446‐22:24. doi:10.1128/msystems.00446-22