Diurnal Variations in Digestion and Flow Drive Microbial Dynamics in the Gut

The human large intestine harbors a highly dynamic microbial ecosystem in which growing microbes regularly replenish biomass lost via feces. Elucidating these population dynamics is important as studies increasingly indicate a direct link between microbial density imbalances in the large intestine and host immune responses, colonic cell physiology, as well as disease development. However, given the strong changes in microbial growth, biomass, and intestinal fluid flow throughout the day, gaining a better understanding of these population dynamics remains a major challenge. Leveraging experimental data on fluid turnover, nutrient supply, and microbial growth, we here derive a biophysical model of microbial population dynamics in the proximal large intestine. We show how the digestion of meals in batches triggers strong fluctuations in fluid movement and bacteria growth. Comparing different model scenarios, we further analyze how the expandable nature of the proximal large intestine, the presence of a pouch-like cecum off major flow paths, and the periodic exit of luminal content via “mass movements” are required in combination to maintain the high microbial population observed in the proximal large intestine. As the microbial population undergoes several bottlenecks followed by rapid growth each day, the effective population size in the proximal large intestine is small, <a:math xmlns:a="http://www.w3.org/1998/Math/MathML"><a:mrow><a:msub><a:mi>N</a:mi><a:mi>e</a:mi></a:msub><a:mo>∼</a:mo><a:msup><a:mrow><a:mn>10</a:mn></a:mrow><a:mn>7</a:mn></a:msup><a:mo>−</a:mo><a:msup><a:mrow><a:mn>10</a:mn></a:mrow><a:mn>11</a:mn></a:msup></a:mrow></a:math>, promoting the rapid evolution of microbes. The diurnal fluctuations in flow also hamper the accumulation of slower-growing bacteria and lead to substantial variations in the uptake of fermentation products by the host. Our findings underscore the complex interplay between population dynamics of the gut microbiota, fluid flow, and bacterial growth with important consequences for the microbiome and the host.