Comparative analysis of beneficial effects of vancomycin treatment on Th1- and Th2-biased mice and the role of gut microbiota.

Abstract

The aim was to understand the time-dependent antibiotic-induced perturbation pattern of gut microbiota and its effect on the innate immune and metabolic profile of the host. Vancomycin was administered at 50mgkg-1 of body weight twice daily for six consecutive days to perturb the gut microbiota of C57BL/6 (Th1-biased) and BALB/c (Th2-biased) mice. Following treatment with vancomycin, we observed a reduction in the abundance of phyla Firmicutes and Bacteroides and an increase in Proteobacteria in the gut for both strains of mice following treatment with vancomycin till day 4. Abundance of Akkermansia muciniphila of Verrucomicrobia phylum also increased, from day 5 onwards following vancomycin treatment. The time-dependent variation of gut microbiota was associated with increased (i) expression of toll-like receptors and inflammatory genes such as TNF-α, IL-6, and IL-17, (ii) gut barrier permeability and (iii) blood glucose level of the host. The results also showed that (i) transplantation of cecal microbiota from vancomycin-treated day 6 mice to day 3 vancomycin-treated mice helped in restoring blood glucose level in C57BL/6 mice and (ii) short-chain fatty acids like acetate, butyrate and propionate changed with the alteration of gut microbiota to induce differential regulation of host immune response. The current results revealed that an increase in A. muciniphila led to decreased inflammation and increased rate of glucose tolerance in the host. The treatment, with vancomycin till day 4, increased expression of inflammatory genes. The continuation of vancomycin for two more days reversed the effects. The effects were significantly more in C57BL/6 than BALB/c mice. The current study established that the treatment with vancomycin till day 4 increased pathogenic bacteria but day 5 onwards provided significant health-related benefits to the host by increasing A. muciniphila more in C57BL/6 than BALB/c mice.