Personalized effects of antibiotics on the human gut microbiome via high-throughput cultivation

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Antibiotics are essential for curing infections. However, they also affect commensal microbes with long term-consequences for the host. It is thus important to study collateral effects of antibiotics. In BioIMPACT, we will test the hypothesis that evolutionary drifts in human gut bacteria due to antibiotic treatment influence ecosystem functions in a personalized manner. Therefore, we will investigate antibiotic-induced changes within human fecal communities at the strain-level using a combination of anaerobic cultivation and sequencing techniques. The work relies on our combined expertise in high-end cultivation approaches, (meta)genomics, and gnotobiology, and is organized in four main areas: (i) antibiotic intervention in humanized mice to study metabolomic- and sequencing-based ecosystem dynamics under controlled conditions; (ii) establishment of personalized collections of cultured bacteria and their genomic landscape at the strain-level; (iii) in-depth phenotyping of drug-bacteria interactions and functional design of synthetic communities; (iv) proof-of-concept functional studies in gnotobiotic mice to test the effect of strain variability on the metabolome and ecosystem challenge by antibiotics. Besides this main objective, the project will also deliver a large amount of data on the diversity and functions of cultured bacteria, which is essential considering that gut microbiome research is hampered by the fact that many microbes and their functions are still unknown. Moreover, the gut microbiota is known to be individual-specific but experimental models do not recapitulate these features, which will also be addressed in BioIMPACT. In summary, this project will deliver novel insights into the ecology and cultured fraction of gut microbiomes and test new concepts for personalized microbiome-based applications using isolates.