Effect of flow and peristaltic mixing on bacterial growth in a gut-like channel

Abstract

The ecology of microbes in the gut has been shown to play important roles in the health of the host. To better understand microbial growth and population dynamics in the proximal colon, the primary region of bacterial growth in the gut, we built and applied a fluidic channel that we call the "minigut." This is a channel with an array of membrane valves along its length, which allows mimicking active contractions of the colonic wall. Repeated contraction is shown to be crucial in maintaining a steady-state bacterial population in the device despite strong flow along the channel that would otherwise cause bacterial washout. Depending on the flow rate and the frequency of contractions, the bacterial density profile exhibits varying spatial dependencies. For a synthetic cross-feeding community, the species abundance ratio is also strongly affected by mixing and flow along the length of the device. Complex mixing dynamics due to contractions is described well by an effective diffusion term. Bacterial dynamics is captured by a simple reaction-diffusion model without adjustable parameters. Our results suggest that flow and mixing play a major role in shaping the microbiota of the colon.

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

“…We argue that hydrodynamic mixing by active contractions of the intestinal walls-continuously observed in the proximal colon (22)-is the most important mechanism stabilizing high bacterial densities (Fig. 2C): In a recent in vitro study (11), it has been shown that hydrodynamic mixing, in combination with bacterial growth, allows maintenance of stable bacterial populations even for high flow rates; here, we discuss the situation in the human gut in SI Appendix, Fig. S2 and section 2.3.…”

“…S1 and section 5.3). Note that the same effective diffusion constant D is used for the small nutrient molecules and the much larger bacterial cells, because in contrast to molecular diffusion, mixing dynamics is similar for both (11). A similar equation is used to describe the total concentration of excreted short chain fatty acids, s, as follows:…”

“…(C) Mixing of luminal contents. Contractions of the intestinal walls can generate local mixing (11,22,58). Based on data on the mixing of radiolabeled dyes in the large intestine (40), we derive that the measured distributions can be approximated by an effective diffusion constant of D ∼ 10 6 μm 2 /s, a value orders of magnitude higher than molecular diffusion (see SI Appendix, Fig.…”

“…At such high flow rates (corresponding to flow velocities of J 30 μm=s; Fig. 2B), bacterial density in the lumen would quickly be depleted unless additional mechanisms are in place to keep them at the stable and high levels observed [10 11 to 10 12 cells per mL (19)] (5,11,20,21). We argue that hydrodynamic mixing by active contractions of the intestinal walls-continuously observed in the proximal colon (22)-is the most important mechanism stabilizing high bacterial densities (Fig.…”

“…Our model is based on a hydrodynamic perspective, which posits that bacterial densities reached in the colon result from a dynamic balance between bacterial growth, flow through the colon, and peristaltic mixing (11). To build the present model, we extensively analyzed literature data on human gut physiology to obtain quantitative estimates for a range of relevant host parameters.…”