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Gut microbial genetic variation modulates host lifespan, sleep, and motor performance

The ISME Journal volume 17, pages 1733–1740 (2023)Cite this article

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Abstract

Recent studies have shown that gut microorganisms can modulate host lifespan and activities, including sleep quality and motor performance. However, the role of gut microbial genetic variation in regulating host phenotypes remains unclear. In this study, we investigated the links between gut microbial genetic variation and host phenotypes using Saccharomyces cerevisiae and Drosophila melanogaster as research models. Our result suggested a novel role for peroxisome-related genes in yeast in regulating host lifespan and activities by modulating gut oxidative stress. Specifically, we found that deficiency in catalase A (CTA1) in yeast reduced both the sleep duration and lifespan of fruit flies significantly. Furthermore, our research also expanded our understanding of the relationship between sleep and longevity. Using a large sample size and excluding individual genetic background differences, we found that lifespan is associated with sleep duration, but not sleep fragmentation or motor performance. Overall, our study provides novel insights into the role of gut microbial genetic variation in regulating host phenotypes and offers potential new avenues for improving health and longevity.

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Fig. 1: Genome-scale screening to identify S. cerevisiae single gene deletion mutants that affect Drosophila lifespan, sleep, and motor performance.
Fig. 2: Relationship between sleep duration and lifespan in Drosophila.
Fig. 3: Catalase A deficiency in S. cerevisiae reduced host sleep duration and lifespan by increasing gut ROS level.
Fig. 4: Antioxidants rescued the shortening of fly lifespan and sleep duration induced by feeding with CTA1-KO yeast.

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All data are available in the main text and the supplementary materials.

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Acknowledgements

We would like to express our gratitude to Dr. Qiang Zhang and Fang Zhang for the helpful discussions.This work was supported by the National Natural Science Foundation of China (81701390, 81902040), Natural Science Foundation of Jiangsu Province (BK20170250), Xuzhou key research and development plan project (KC19057, KC22096) and the Jiangsu University Students Innovation and Entrepreneurship Training Program (202010313026Z).

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Author notes

  1. These authors contributed equally: Ying Li, Simin Xu, Liying Wang, Hao Shi.

Authors and Affiliations

  1. Medical Technology College, Xuzhou Medical University, Xuzhou, China

    Ying Li

  2. Department of Biological Sciences, Faculty of Science, National University of Singapore, Singapore, 117543, Singapore

    Simin Xu

  3. Xuzhou Engineering Research Center of Medical Genetics and Transformation, Key Laboratory of Genetic Foundation and Clinical Application, Department of Genetics, Xuzhou Medical University, Xuzhou, China

    Liying Wang & Zuobin Zhu

  4. The First Clinical College, Xuzhou Medical University, Xuzhou, China

    Hao Shi, Han Wang & Mengqiong Deng

  5. School of Anesthesiology, Xuzhou Medical University, Xuzhou, China

    Ziyi Fang, Yufan Hu, Jiayu Jin & Yujie Du

  6. Laboratory Medicine, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, 510080, China

    Liang Wang

  7. The Center for Precision Health, School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, 6027, Australia

    Liang Wang

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Contributions

YL, SX, LW, and ZZ designed research; YL, LW, HS, HW, ZF, YH, JJ, DJ, and MD performed research; SX contributed to analytical workflows; SX, LW, and HS analyzed the data; ZZ and SX wrote the paper; ZZ contributed to funding.

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Correspondence to Liang Wang or Zuobin Zhu.

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Li, Y., Xu, S., Wang, L. et al. Gut microbial genetic variation modulates host lifespan, sleep, and motor performance. ISME J 17, 1733–1740 (2023). https://doi.org/10.1038/s41396-023-01478-x

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