Effects of common antibiotics on representative gut bacterial strains associated with inflammatory bowel disease

Abstract

Abstract Background Inflammatory Bowel Disease (IBD), a group of multifactorial diseases marked by chronic inflammation of the gastrointestinal tract, is characterized by an altered gut microbial community composition that is enriched in opportunistic and pathogenic species, such as Bacteroides fragilis and adherent-invasive Escherichia coli strains. To better understand the consequences of using antibiotics to suppress these harmful species, we quantified the response of three bacterial species representative of a healthy gut microbiome, as well as two species typically enriched in IBD to five selected antibiotics that are widely employed against anaerobes. Results We found that the adherent-invasive Escherichia coli LF82 strain and the type strains of the opportunistic Bacteroides species B. fragilis and B. thetaiotaomicron are resistant to even high doses of several of the tested antibiotics whereas the type strains of the probiotic butyrate producer Roseburia intestinalis and the acetogen Blautia hydrogenotrophica are sensitive to the majority of the tested antibiotics at low concentrations. We performed a Bayesian parameter estimation of a parsimonious mechanistic growth model. The effects of the antibiotics on lag phase, growth rate, and death rate varied across compounds in a manner consistent with their modes of action. For example, metronidazole, which inhibits DNA synthesis, reduced the growth rate, whereas meropenem, which inhibits cell wall synthesis, increased the death rate in several cases. In contrast, eravacycline, piperacillin/tazobactam and rifampin exhibited variable and species-dependent effects on the growth dynamics. Conclusion The observation that opportunistic strains in monoculture are resistant to several tested antibiotics in contrast to commensals questions the use of broad-spectrum antibiotics for microbiome modulation in gastrointestinal diseases and motivates the need for targeted strategies to reshape dysbiotic microbial communities.