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Deciphering microbial interactions in synthetic human gut microbiome communities
Authors:Ophelia S Venturelli  Ryan H Hsu  Rebecca Lau  Benjamin P Bowen  Susan Hromada  Trent Northen  Adam P Arkin
Affiliation:1. Department of Biochemistry, University of Wisconsin‐Madison, Madison, WI, USA;2. California Institute for Quantitative Biosciences, University of California Berkeley, Berkeley, CA, USA;3. Environmental Genomics and Systems Biology, Lawrence Berkeley National Laboratory, Berkeley, CA, USA;4. Department of Bioengineering, University of California Berkeley, Berkeley, CA, USA;5. Energy Biosciences Institute, University of California Berkeley, Berkeley, CA, USA
Abstract:The ecological forces that govern the assembly and stability of the human gut microbiota remain unresolved. We developed a generalizable model‐guided framework to predict higher‐dimensional consortia from time‐resolved measurements of lower‐order assemblages. This method was employed to decipher microbial interactions in a diverse human gut microbiome synthetic community. We show that pairwise interactions are major drivers of multi‐species community dynamics, as opposed to higher‐order interactions. The inferred ecological network exhibits a high proportion of negative and frequent positive interactions. Ecological drivers and responsive recipient species were discovered in the network. Our model demonstrated that a prevalent positive and negative interaction topology enables robust coexistence by implementing a negative feedback loop that balances disparities in monospecies fitness levels. We show that negative interactions could generate history‐dependent responses of initial species proportions that frequently do not originate from bistability. Measurements of extracellular metabolites illuminated the metabolic capabilities of monospecies and potential molecular basis of microbial interactions. In sum, these methods defined the ecological roles of major human‐associated intestinal species and illuminated design principles of microbial communities.
Keywords:ecology  human gut microbiome  mathematical modeling  microbial community  microbial interaction
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