Abstract
Host-microbial metabolic interactions have been recognized as an essential factor in host health and disease. Genome-scale metabolic modeling approaches have made important contributions to our understanding of the interactions in such communities. One particular such modeling approach is BacArena, in which metabolic models grow, reproduce, and interact as independent agents in a spatiotemporal metabolic environment. Here, we present a modeling application of BacArena, a virtual colonic environment, which reveals spatiotemporal metabolic interactions in a computational colonic environment. This environment resembles the crypt space together with the mucus layers, the lumen, and fluid dynamics. Our proof-of-principle experiments include mono-colonization simulations of context-specific colonic cells and simulations of context-specific colonic cells with the SIHUMIx minimal model microbiome. Our simulations propose host-microbial and microbial-microbial interactions that can be verified based on the literature. Most importantly, the Virtual Colon offers visualization of interactions through time and space, adding another dimension to the genome-scale metabolic modeling approaches. Lastly, like BacArena, it is freely available and can be easily adapted to model other spatially structured environments (http://www.github.com/maringos/VirtualColon).IMPORTANCEInteractions between the human body and gut microbes are crucial for health and disease. We present the Virtual Colon, an extension of the individual-based microbiome modeling approach BacArena that mimics key features of the colon, including the crypts, mucus layers, lumen, and fluid flow. Using this model, we simulate gut environments including host cells with bacterial species alone and with a simplified gut microbiota (SIHUMIx). These simulations reveal patterns of host-microbe and microbe-microbe interactions that align with known findings. A key strength of the Virtual Colon is its ability to show how interactions unfold over time and space, offering new insights beyond traditional modeling approaches. The Virtual Colon is freely available and can be adapted to other structured biological environments (http://www.github.com/maringos/VirtualColon).