Comparative metagenomic analysis following treatment with vancomycin in C57BL/6 and BALB/c mice to elucidate host immunity and behavior

The gut is the largest reservoir of the resident microbiota. The microbiota can affect the host behavior and immunity. While the consequence of treatment with antibiotics on the gut microbiota can be destructive but can be utilized as a tool to understand the host immunity and behavior. The magnitude of perturbation and time needed for the restoration of gut microbiota can depend on the immune bias of the host. In the current study, we therefore, observed the perturbation and restoration kinetics of gut microbiota following treatment with vancomycin and its effect on the host physiology in both Th1-(C57BL/6) and Th2-(BALB/c) biased mice. A comparative metagenomic analysis revealed that the treatment with vancomycin caused a significant decrease in the abundance of Firmicutes and Bacteroidetes phyla and an initial increase in Proteobacteria. Increase in Proteobacteria decreased with continued treatment with vancomycin to result into a significant rise in Verrucomicrobia phylum. We established the patterns of gut microbiota alteration and its effect on a) the behavior of mice, b) expression of key brain molecules and b) immunity related genes. We followed the gut microbiome restoration for a period of two months following withdrawal of treatment with vancomycin. Maximum restoration (>70%) of gut microbiota happened by the 15 th day of withdrawal. BALB/c mice showed a more efficient restoration of gut microbiota compared to C57BL/6 mice. The results, in general, revealed that along with the restoration of major gut microbes, important physiological and behavioral changes of both mice strains returned to the normal level.