Cooperative growth in microbial communities is a driver of multistability

Abstract Microbial communities often exhibit more than one possible stable composition for the same set of external conditions. In the human microbiome, these persistent changes in species composition and abundance are associated with health and disease states, but the drivers of these alternative stable states remain unclear. Here we experimentally demonstrate that a cross-kingdom community, composed of six species relevant to the respiratory tract, displays four alternative stable states each dominated by a different species. In pairwise coculture, we observe widespread bistability among species pairs, providing a natural origin for the multistability of the full community. In contrast with the common association between bistability and antagonism, experiments reveal many positive interactions within and between community members. We find that multiple species display cooperative growth, and modeling predicts that this could drive the observed multistability within the community as well as non-canonical pairwise outcomes. A biochemical screening reveals that glutamate either reduces or eliminates cooperativity in the growth of several species, and we confirm that such supplementation reduces the extent of bistability across pairs and reduces multistability in the full community. Our findings provide a mechanistic explanation of how cooperative growth rather than competitive interactions can underlie multistability in microbial communities.