What Shapes the Lives of the Gut’s Microbial Inhabitants
The human body harbors large numbers of bacteria—about as many as human cells—most of which are located in the gut, mainly in the colon. Together, diverse microorganisms including multiple species and strains of bacteria constitute the gut microbiota, which is thought to play a central role in human health, affecting the immune response and the progression of different diseases. However, despite a vast body of microbiota studies based on gene sequencing and on experiments with animal models, the dynamics of microbial populations in the human gut remain poorly understood. Alinaghi Salari of the University of Toronto and James Cremer of Stanford University have now proposed a biophysical model of the gut environment that incorporates a broad set of features of the human large intestine [1]. Using the model, the researchers pinpoint how different factors—nutrient supply and digestion, bacterial growth, and a biomass transport fluctuating throughout the day—impact the overall gut microbiota population dynamics (Fig. 1).
The gut microbiota interact in a complex way with the body of a human or other animal. Beyond helping the host to digest food, the microbiota are involved in the maturation of the host immune system and affect the proliferation of the host’s cells as well as neurologic signaling. The composition of the gut microbiota can have an important impact on the health of the host: Some composition anomalies are associated with diseases such as obesity and type 2 diabetes. The gut microbiota are also connected to a major public health problem: the development of antibiotic resistance, both in humans and in livestock. Oral antibiotic treatments can foster the growth of antibiotic-resistant strains in the microbiota, and antibiotic-resistance genes might be transferred from one bacterial species to another within the microbiota. Given such important implications, the study of the gut microbiota is an extremely active area of research.
Gut bacteria consume food, grow, interact, and evolve within their natural environment. Understanding this interplay is key to determining what controls the composition of the gut microbiota and might be helpful in designing interventions that modify this composition to improve the host’s health. The gut environment is complex from a physical point of view. It features an overall directional hydrodynamic flow along the gut’s main axis, as the contents of the gut gradually move forward, with most bacteria being carried along this flow. Another characteristic feature of gut hydrodynamics is the mixing and recirculation caused by contractions of muscles around the gut. These motions promote digestion. The concentrations of food and bacteria also display strong gradients along the gut’s main axis. After food enters upstream, simple nutrients are first absorbed by the body, and then more complex molecules are broken down by bacteria, which in turn divide and become more numerous. Eventually, the remaining food exits the system, together with many bacteria. What’s more, the gut environment features important temporal variability, since food is consumed at mealtimes, and bowel movements also occur at discrete times. Physics-based models are currently playing a key role in understanding how this complex gut environment shapes the microbiota’s abundance, composition, and dynamics. In particular, there is a strong need for theoretical models that shed light on the impact of each environmental factor on the microbiota.
The new work by Salari and Cremer builds on pioneering models of the gut microbiota previously developed by Cremer and colleagues. Such models accounted for the coupling of microbial growth and fluid dynamics in the gut [2, 3] and gave insight into how gradients of food and nutrient concentrations are established in the gut. Salari and Cremer’s new model is more complete. For one thing, it explicitly takes into account the radial dimension of the gut—viewed as a cylinder—as well as the dynamical variations of the radius induced by muscle contractions, which makes the gut expandable. Within this model, the researchers investigate the impact of the gut environment on the population of gut bacteria by performing simulations based on finite-element methods (Fig. 2). They pinpoint various factors that together make it possible for the proximal colon (the first and middle part of the colon) to maintain a high but varying microbial population. Such factors include time-dependent food intake (the consumption of three meals during the day), the expandable volume of the gut, the periodic mass movements of gut content, and the presence of a pouch-like structure protected from major flow (known in anatomy as the cecum). Interestingly, unless these physical ingredients are considered together, the simulations would predict the decay of the bacterial population, which isn’t consistent with observations. Accounting for all these physical factors simultaneously is clearly key to recovering the features observed in biology.
The insights into the key biophysical ingredients that affect microbial growth dynamics provide a window into how the host’s physiology can control this microbial growth. Such new insights open many directions for further fundamental and applied investigations, potentially including the design of medical interventions that target the gut microbiota. In particular, the research might have important implications for the study of the ecology of gut bacteria and of their interactions (among themselves and with the host). An important conclusion involves bacteria that rely on cross-feeding (that is, they feed on products of the metabolism of other bacterial species that break down the complex nutrients produced by fermentation in the colon). Salari and Cremer’s new model suggests that these bacteria cannot accumulate efficiently because of their slower growth. Thus, most of these nutrients remain available to the host as a source of energy.
Finally, the work has important implications for understanding the Darwinian evolution of the gut microbiota. Specifically, the researchers evaluate the “effective” population size (number of bacteria) that results from their model. This number, which represents the size of an equivalent, well-mixed population that doesn’t vary in time, is an important indicator of how mutants take over the bacterial population in the gut [4, 5]. The new estimates correspond to an effective population size that is smaller than expected—a finding relevant to our understanding of bacterial diversity and species turnover and to the development of more detailed models of evolution in the gut microbiota.
References
- A. Salari and J. Cremer, “Diurnal variations in digestion and flow drive microbial dynamics in the gut,” PRX Life 3, 023012 (2025).
- J. Cremer et al., “Effect of flow and peristaltic mixing on bacterial growth in a gut-like channel,” Proc. Natl. Acad. Sci. U.S.A. 113, 11414 (2016).
- J. Cremer et al., “Effect of water flow and chemical environment on microbiota growth and composition in the human colon,” Proc. Natl. Acad. Sci. U.S.A. 114, 6438 (2017).
- D. Labavić et al., “Hydrodynamic flow and concentration gradients in the gut enhance neutral bacterial diversity,” Proc. Natl. Acad. Sci. U.S.A. 119 (2021).
- O. M. Ghosh and B. H. Good, “Emergent evolutionary forces in spatial models of luminal growth and their application to the human gut microbiota,” Proc. Natl. Acad. Sci. U.S.A. 119 (2022).