Abstract
Gut microbiota play a critical role in orchestrating metabolic homeostasis of the host. However, the crosstalk between host and microbial symbionts in small mammals are rarely illustrated. We used male Brandt’s voles (Lasiopodomys brandtii) to test the hypothesis that gut microbiota and host neurotransmitters, such as norepinephrine (NE), interact to regulate energetics and thermogenesis during cold acclimation. We found that increases in food intake and thermogenesis were associated with increased monoamine neurotransmitters, ghrelin, short-chain fatty acids, and altered cecal microbiota during cold acclimation. Further, our pair-fed study showed that cold temperature can alter the cecal microbiota independently of overfeeding. Using cecal microbiota transplant along with β3-adrenoceptor antagonism and PKA inhibition, we confirmed that transplant of cold-acclimated microbiota increased thermogenesis through activation of cAMP–PKA–pCREB signaling. In addition, NE manipulation induced a long-term alteration in gut microbiota structure. These data demonstrate that gut microbiota-NE crosstalk via cAMP signaling regulates energetics and thermogenesis during cold acclimation in male Brandt’s voles.
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Data availability
Raw sequence data are deposited in the NCBI Sequence Read Archive under accession PRJNA555499, PRJNA555506, PRJNA555511, and PRJNA555551.
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Acknowledgements
We appreciate the very helpful and constructive comments and suggestions from the three anonymous reviewers and the editor for improving the manuscript. We are grateful to Prof. Zuoxin Wang and Meghan Donovan from Department of Psychology and Program in Neuroscience, Florida State University for the comments and careful editing. We thank Jianfeng Wang from Beijing Nebula Medical Laboratory Co., Ltd. for helps in 16S rRNA gene sequencing and analyses. We also thank Prof. Jianxu Zhang and Dr. Yaohua Zhang for supplying some chemicals and technique, and thank all the members of Animal Physiological Ecology Group for their help in the experiments and discussions. This research was supported by the National Natural Science Foundation of China (Nos. 31770440 and 31772461), and the Beijing Natural Science Foundation (5172024).
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X-YZ and D-HW designed the studies. T-BB and X-YZ conducted the experiments. T-BB, X-YZ, JW, and X-WQ performed the measurements of SCFAs and neurotransmitters. T-BB and X-YZ analyzed the data. TBB, X-YZ, and KD made the figures. T-BB, X-YZ, and D-HW wrote the paper. All authors read and approved the final manuscript.
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Bo, TB., Zhang, XY., Wen, J. et al. The microbiota–gut–brain interaction in regulating host metabolic adaptation to cold in male Brandt’s voles (Lasiopodomys brandtii). ISME J 13, 3037–3053 (2019). https://doi.org/10.1038/s41396-019-0492-y
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DOI: https://doi.org/10.1038/s41396-019-0492-y
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