Emergence of community behaviors in the gut microbiota upon drug treatment

• DOI: 10.1101/2023.06.13.544832
• Publication Date: 2023-06-14T16:05:10Z
• Authors: Sarela Garcia-San...; Michael Kuhn; Saravanan Devendran; Lisa Maier; Marja Driessen; André Mateus; Eleonora Mastrorilli; Ana Rita Brochado; Mikhail M. Savitski; Kiran R. Patil; Michael Zimmermann; Peer Bork; Athanasios Typas
• Keywords: Cardiovascular and Metabolic Diseases; Molecular Processes and Therapies [Topic 2]

Summary Pharmaceuticals can directly inhibit the growth of gut bacteria, but degree such interactions manifest in complex community settings is an open question. Here we compared effects 30 drugs on a 32-species synthetic with their each member isolation. While most individual drug–species remained same context, communal behaviors emerged 26% all tested cases. Cross-protection, during which drug-sensitive species became protected community, was 6-times more frequent than cross-sensitization, converse phenomenon. Cross-protection decreased and cross-sensitization increased at higher drug concentrations, suggesting that resilience microbial communities collapse when perturbations get stronger. By metabolically profiling drug-treated communities, showed both biotransformation bioaccumulation contribute mechanistically to protection. As proof-of-principle, molecularly dissected prominent case: expressing specific nitroreductases degraded niclosamide, thereby protecting themselves sensitive members.