LEADING: Low-level Exposure to Antibiotics Disturbs Interactions among Non-pathogenic bacteria in the Gastrointestinal tract

Our bodies are homes to billions of microbes, most of which are beneficial to us, forming the so-called human microbiome.

This project will uncover interactions between the bacteria in the microbiome that are important for its stability and resilience to colonization by pathogens.

To reduce the variability present in human cohorts and avoid excessive animal experiments, model communities representing different compartments of the human microbiome will be used.

Specifically, we will: i) establish model systems and bacterial communities for the human stomach and intestine, ii) investigate how antibiotic exposure changes interactions in these model communities, iii) evaluate the effects of antibiotic disturbances on the community resilience to colonization by a new species or strain, and iv) identify genes important for bacterial colonization or resilience to invasion in the human microbiome.

The project will combine cell culturing techniques with high-throughput sequencing approaches (metatranscriptomics, 16S rRNA sequencing and transposon mutant sequencing) to find specific species and genes that are important for stable interactions. The project will provide the foundation for future in vivo studies of bacterial interactions in the human body.

Understanding how disturbances to these interactions cause imbalances in the microbiota will provide clues to what causes a diverse range of diseases linked to the human microbiome, including colon cancer, depression, IBS and IBD.