Effect of water flow and chemical environment on microbiota growth and composition in the human colon

Significance

The human gut is populated by a dense microbial population, strongly impacting health and disease. Metagenomic sequencing has led to crucial insights into microbiota changes in response to various perturbations, but a mechanistic understanding of these changes is largely missing. As the composition of the gut microbiota is a consequence of bacterial growth, we propose an approach that focuses on bacterial growth in the human large intestine and the physiological factors influencing it. Using a combination of experimental analysis and quantitative simulations, we explain the observed variation in microbiota composition among healthy humans and the dominant role of nutrient inflow and stool consistency. Our quantitative modeling framework is a step toward a predictive understanding of microbiota dynamics in the human host.

Abstract

The human gut harbors a dynamic microbial community whose composition bears great importance for the health of the host. Here, we investigate how colonic physiology impacts bacterial growth, which ultimately dictates microbiota composition. Combining measurements of bacterial physiology with analysis of published data on human physiology into a quantitative, comprehensive modeling framework, we show how water flow in the colon, in concert with other physiological factors, determine the abundances of the major bacterial phyla. Mechanistically, our model shows that local pH values in the lumen, which differentially affect the growth of different bacteria, drive changes in microbiota composition. It identifies key factors influencing the delicate regulation of colonic pH, including epithelial water absorption, nutrient inflow, and luminal buffering capacity, and generates testable predictions on their effects. Our findings show that a predictive and mechanistic understanding of microbial ecology in the gut is possible. Such predictive understanding is needed for the rational design of intervention strategies to actively control the microbiota.