Modifications to the gut microbiome in response to various anti-bacterial therapeutics.

Antibiotics revolutionized the treatment of infectious diseases, however it is now clear that broad spectrum antibiotics alter the composition and function of the host's microbiome. The microbiome plays a key role in human health and its perturbation is increasingly recognized as contributing to many human diseases. Wide spread broad spectrum antibiotic use has also resulted in the emergence of multi-drug resistant pathogens, spurring development of pathogen-specific strategies such as monoclonal antibodies (mAbs) to combat bacterial infection. Not only are pathogen specific approaches not expected to induce resistance in non-targeted bacteria, but they are hypothesized to have minimal impact on the gut microbiome. Here, we compare the effects of antibiotics, pathogen specific mAbs or their controls (saline or c-IgG) on the gut microbiome of 7-week-old, female, C57BL/6 mice. The magnitude of change in taxonomic abundance, bacterial diversity, and bacterial metabolites including short chain fatty acids (SCFA) and bile acids in the fecal pellets from mice treated with pathogen-specific mAbs was no different from animals treated with saline or an IgG control. Conversely, dramatic changes were observed in the relative abundance, as well as alpha- and beta-diversity, of the fecal microbiome, and bacterial metabolites in the feces of all antibiotic treated mice. Taken together, these results indicate that pathogen-specific mAbs do not alter the fecal microbiome like broad-spectrum antibiotics and may represent a safer, more targeted approach to antibacterial therapy.