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Vancomycin-Induced Changes in Host Immunity and Behavior: Comparative Genomic and Metagenomic Analysis in C57BL/6 and BALB/c Mice

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Abstract

Background

The consequence of treatment with antibiotics on the gut microbiota can be destructive. The antibiotics, however, can be utilized to understand the role of gut microbiota on the host physiology.

Aim

Earlier, we reported the efficacy of vancomycin in gut microbiota perturbation. We continued to understand the effect of restoration kinetics of perturbed gut microbiota on the immunity and behavior of Th1 (C57BL/6)- and Th2 (BALB/c)-biased mice.

Methods

We studied restoration kinetics of the gut microbiota for two months following the withdrawal of vancomycin treatment in both mice strains. We analyzed cecal microbiome composition, different behavioral assays, and expression of select genes associated with stress and barrier function in gut and brain.

Results

Metagenomic analysis of gut microbiota revealed that the treatment with vancomycin caused a significant decrease in the relative abundance of Firmicutes and Bacteroidetes phyla with a time-dependent increase in Proteobacteria and Verrucomicrobia phyla. Maximum restoration (> 70%) of gut microbiota happened by the 15th day of withdrawal of vancomycin. BALB/c mice showed a more efficient restoration of gut microbiota compared to C57BL/6 mice. We established the correlation patterns of gut microbiota alteration and its effect on (a) the behavior of mice, (b) expression of key brain molecules, and (c) immunity-related genes.

Conclusions

The results revealed that the gut microbiome profiling, behavior, and immune responses varied significantly between Th1- and Th2-biased mice. By withdrawing the treatment with vancomycin of major gut microbes, important physiological and behavioral changes of both mice strains returned to the normal (untreated control) level.

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Code availability

SRA accession: PRJNA566053, PRJNA660929, PRJNA660934.

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Acknowledgments

The current work (necessary resources to perform the experiment and the infrastructure for the laboratory) was supported by the intra-mural core funding from DAE, GoI through parent institute National Institute of Science Education and Research (NISER). The current work was not supported through any other extra-mural funding except the Ph.D. fellowship to PR by the Council of Scientific and Industrial Research (CSIR), GoI. There is no other funding support to assist the preparation of the manuscript.

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Authors and Affiliations

  1. School of Biological Sciences, National Institute of Science Education and Research (NISER), HBNI, P.O. - Bhimpur-Padanpur, Jatni, Khurda, Odisha, 752050, India

    Pratikshya Ray, Uday Pandey, Debasmita Das & Palok Aich

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  1. Pratikshya Ray
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  2. Uday Pandey
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  3. Debasmita Das
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  4. Palok Aich
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Contributions

PR and UP contributed equally and performed the experiments and drafted the manuscript. DD was associated with behavior related experiments. PR and PA designed the experiments. PA supervised the studies and finalized the manuscript.

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Correspondence to Palok Aich.

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The authors would like to acknowledge the support of Animal House in maintaining and assisting the experiments with the animals.

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Ray, P., Pandey, U., Das, D. et al. Vancomycin-Induced Changes in Host Immunity and Behavior: Comparative Genomic and Metagenomic Analysis in C57BL/6 and BALB/c Mice. Dig Dis Sci 66, 3776–3791 (2021). https://doi.org/10.1007/s10620-020-06729-x

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