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The effect of different combinations of antibiotic cocktails on mice and selection of animal models for further microbiota research

  • Applied microbial and cell physiology
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Abstract

The gut microbiota is closely related to host health and disease. However, there are no suitable animal models available at present for exploring its functions. We analyzed the effect of 3 different antibiotic cocktails (ABx) via two administration routes on the composition of murine gut microbiota, as well as on the general physiological and metabolic indices. High-throughput 16S rRNA sequencing showed that ABx treatment altered the gut microbiota community structure, and also caused low-degree inflammation in the colon. In addition, ad libitum administration of antibiotics depleted the gut microbiota more effectively compared to direct oral gavage, especially with 3ABx. The ABx treatment also had a significant impact on renal and liver functions, as indicated by the altered serum levels of creatinine, urea, total triglycerides, and total cholesterol. Finally, Spearman’s correlation analysis showed that the predominant bacterial genera resulting from ABx intervention, including Lactobacillus, Roseburia, and Candidatus-Saccharimonas, were negatively correlated with renal function indices. Taken together, different antibiotic combinations and interventions deplete the gut microbiota and induce physiological changes in the host. Our findings provide the basis for developing an adaptive animal model for studying gut microbiota.

Key points

• Ad libitum administration of 3ABx can effectively deplete intestinal microbiota.

• ABx treatment may have slight effect on renal and liver function.

• The levels of urea and creatinine correlated with the growth of Roseburia.

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Data availability

Data from the study are available in NCBI-SRA under accession number PRJNA 661221.

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Acknowledgments

Not applicable.

Funding

This work was supported by grants from the National Natural Science Foundation of China (81700487 and 81871905), the Guangdong Medical Science and Technology Research Fund (A2019243), the Guangzhou Planned Project of Science and Technology (202002020012, 202002030288, 202002030293) and the Innovative Clinical Technique of Guangzhou (2019GX05).

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Authors

Contributions

JX and HMX contributed equally to this article. JX and HMX involved in design of the study and drafting of the article; YP and CZ involved in statistical analysis and interpretation of the data; HLZ and WQH participated the animal experiments and recorded general status; HLH and JH performed the sample collection and DNA extraction; YLD and YJZ interpreted the data and revision of the article; YLZ and YQN planned and directed the project and interpreted the results. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to You-lian Zhou or Yu-qiang Nie.

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Institutional animal care and use committee statement

The study was approved by Guangdong Medical Laboratory Animal Center (GDMLAC; Certificate number SYXK 2013-0002). All subsequent studies were performed in accordance with the guidelines approved by the Animal Ethics Committee of GDMLAC. The protocols were approved by the Committee on the Ethics of Animal Experiments of GDMLAC.

Conflict of interest

The authors declare that they have no competing interests.

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Xu, J., Xu, Hm., Peng, Y. et al. The effect of different combinations of antibiotic cocktails on mice and selection of animal models for further microbiota research. Appl Microbiol Biotechnol 105, 1669–1681 (2021). https://doi.org/10.1007/s00253-021-11131-2

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  • DOI: https://doi.org/10.1007/s00253-021-11131-2

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