Analysis of Host and Microbiome Responses to Antibiotics Reveals Microbiota-Independent Effects on Gut Immune Response

Antibiotics are thought to affect host physiology by altering the gut microbiota. But which effects of antibiotics are microbiota-dependent or -independent is not clear. Here, we present a resource encompassing host and microbiota response to antibiotic treatment and computational tools to analyze them. We show how antibiotic administration routes affect host and microbiota responses and how combining antibiotics alters their individual activity. We developed CompoRes, a tool to determine whether perturbation affects the host directly or via the microbiota, and discovered microbiota-independent effects of antibiotic treatment. We found that circadian expression of MHC class II in the colon is functional in germ-free mice and is controlled by feeding via glucose. This expression pattern was lost during vancomycin treatment as the antibiotic altered feeding behaviour in a microbiota-independent manner. Together, our study provides tools for analysis of host response to different microbiota compositions which can also identify microbiota-independent effects of perturbations.