Abstract The human large intestine contains a highly dynamic microbial ecosystem, where growing cells replenish the biomass regularly lost via feces. Growth is primarily fueled by complex carbohydrates, which enter together with luminal fluids from the small intestine, depending on meal intake and with strong variations throughout the day. To elucidate how these variations shape microbial population dynamics, we introduce a mathematical model incorporating intestinal fluid flow, gut motility, and microbial growth. The model findings demonstrate how the expandable nature of the proximal colon, the presence of a pouch-like cecum, and the periodic exit of luminal contents in large batches in combination maintain a stable microbial population in the proximal large intestine, making it the primary region of microbial growth along the gut. The system promotes an efficient growth filter, fostering the proliferation of fast-growing primary fermenters while washing out slower-growing species. The microbial population also undergoes several daily bottlenecks, resulting in a small effective population size, N e ∼ 10 7 −10 11 cells, shaping evolution and competition dynamics. Diurnal fluctuations further cause substantial flow-dependent variations in the host’s uptake of fermentation products, the most abundant microbial metabolites constituting an important energy source for the host. These findings underscore the highly intertwined and rapid turnover dynamics of the gut microbiota, set by microbial and host-controlled characteristics, and of preeminent importance for a mechanistic understanding of host-microbiota interactions.

Diurnal variations in microbial population dynamics along the human large intestine