Integrated culturing, modeling and transcriptomics uncovers complex interactions and emergent behavior in a three-species synthetic gut community

整合培养、建模和转录组学技术揭示了三种物种合成肠道群落中复杂的相互作用和涌现行为

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作者:Kevin D'hoe # ,Stefan Vet # ,Karoline Faust # ,Frédéric Moens ,Gwen Falony ,Didier Gonze ,Verónica Lloréns-Rico ,Lendert Gelens ,Jan Danckaert ,Luc De Vuyst # ,Jeroen Raes #

Abstract

The composition of the human gut microbiome is well resolved, but predictive understanding of its dynamics is still lacking. Here, we followed a bottom-up strategy to explore human gut community dynamics: we established a synthetic community composed of three representative human gut isolates (Roseburia intestinalis L1-82, Faecalibacterium prausnitzii A2-165 and Blautia hydrogenotrophica S5a33) and explored their interactions under well-controlled conditions in vitro. Systematic mono- and pair-wise fermentation experiments confirmed competition for fructose and cross-feeding of formate. We quantified with a mechanistic model how well tri-culture dynamics was predicted from mono-culture data. With the model as reference, we demonstrated that strains grown in co-culture behaved differently than those in mono-culture and confirmed their altered behavior at the transcriptional level. In addition, we showed with replicate tri-cultures and simulations that dominance in tri-culture sensitively depends on the initial conditions. Our work has important implications for gut microbial community modeling as well as for ecological interaction detection from batch cultures. Keywords: Blautia hydrogenotrophica; Faecalibacterium prausnitzii; Roseburia intestinalis; computational biology; infectious disease; microbiology; systems biology.

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