The spatial organization of gut microbiota influences both microbial abundances and host-microbe interactions, but the underlying rules relating bacterial dynamics to large-scale structure remain unclear. To this end, we studied experimentally and theoretically the formation of three-dimensional bacterial clusters, a key parameter controlling susceptibility to intestinal transport and access to the epithelium. Inspired by models of structure formation in soft materials, we sought to understand how the distribution of gut bacterial cluster sizes emerges from bacterial-scale kinetics. Analyzing imaging-derived data on cluster sizes for eight different bacterial strains in the larval zebrafish gut, we find a common family of size distributions that decay approximately as power laws with exponents close to -2, becoming shallower for large clusters in a strain-dependent manner. We show that this type of distribution arises naturally from a Yule-Simons-type process in which bacteria grow within clusters and can escape from them, coupled to an aggregation process that tends to condense the system toward a single massive cluster, reminiscent of gel formation. Together, these results point to the existence of general, biophysical principles governing the spatial organization of the gut microbiome that may be useful for inferring fast-timescale dynamics that are experimentally inaccessible.
Keywords: aggregation; cluster size; gut microbiota; infectious disease; microbiology; physics of living systems; zebrafish.
The human gut is home to vast numbers of bacteria that grow, compete and cooperate in a dynamic, densely packed space. The spatial arrangement of organisms – for example, if they are clumped together or broadly dispersed – plays a major role in all ecosystems; but how bacteria are organized in the human gut remains mysterious and difficult to investigate. Zebrafish larvae provide a powerful tool for studying microbes in the gut, as they are optically transparent and anatomically similar to other vertebrates, including humans. Furthermore, zebrafish can be easily manipulated so that one species of bacteria can be studied at a time. To investigate whether individual bacterial species are arranged in similar ways, Scholmann and Parthasarathy exposed zebrafish with no gut bacteria to one of eight different strains. Each species was then monitored using three-dimensional microscopy to see how the population shaped itself into clusters (or colonies). Schlomann and Parthasarathy used this data to build a mathematical model that can predict the size of the clusters formed by different gut bacteria. This revealed that the spatial arrangement of each species depended on the same biological processes: bacterial growth, aggregation and fragmentation of clusters, and expulsion from the gut. These new details about how bacteria are organized in zebrafish may help scientists learn more about gut health in humans. Although it is not possible to peer into the human gut and watch how bacteria behave, scientists could use the same analysis method to study the size of bacterial colonies in fecal samples. This may provide further clues about how microbes are spatially arranged in the human gut and the biological processes underlying this formation.
© 2021, Schlomann and Parthasarathy.