Multistability driven by cooperative growth in microbial communities

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Abstract

Microbial communities often exhibit more than one possible stable composition for the same set of external conditions 1-7 . In the human microbiome, persistent changes in species composition and abundance are associated with health and disease states 8 . The main drivers of these alternative stable states remain relatively unknown 9 . 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 self-facilitation, or cooperative growth, and modeling predicts that this could drive the observed multistability within the community as well as non-canonical pairwise outcomes. A tailored biochemical screening assay reveals that glutamate supplementation 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.

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  1. Our simplified model community provides a mechanistic explanation of how cooperation-driven multistability can be generated in multispecies contexts.

    Thank you for this very interesting study. The work is well explained and the high quality of the figures makes this work very enjoyable to read.

  2. We showed that competing a six-species community at equal initial abundances leads to substantial outcome variability among replicates.

    All the experiments have been carried out in liquid medium, while the natural environment of this microcosm might be closer to a solid environment. It could be interesting for the authors to briefly comment whether they would expect similar observations for growth on solid medium where microbial community structure might be important.

  3. After five growth cycles

    It is mentioned in the Methods section, that OD was measured at the end of each cycle. Do the authors observe any interesting patterns of OD depending on the community composition outcomes?

  4. we selected a set of six cross-kingdom species that includes both commensals and pathogens found in the human respiratory tract as a model system

    While this is briefly addressed in the Discussion section, it could be interesting to have a little more context about the choice of these species and their ecology. It could also be informative to know if (or how) the inoculation ratios used here would are representative of the natural community.