Indole produced during dysbiosis mediates host-microorganism chemical communication
Abstract
An imbalance of the gut microbiota, termed dysbiosis, has a substantial impact on host physiology. However, the mechanism by which host deals with gut dysbiosis to maintain fitness remains largely unknown. In Caenorhabditis elegans, Escherichia coli, which is its bacterial diet, proliferates in its intestinal lumen during aging. Here, we demonstrate that progressive intestinal proliferation of E. coli activates the transcription factor DAF-16, which is required for maintenance of longevity and organismal fitness in worms with age. DAF-16 up-regulates two lysozymes lys-7 and lys-8, thus limiting the bacterial accumulation in the gut of worms during aging. During dysbiosis, the levels of indole produced by E. coli are increased in worms. Indole is involved in the activation of DAF-16 by TRPA-1 in neurons of worms. Our finding demonstrates that indole functions as a microbial signal of gut dysbiosis to promote fitness of the host.
Data availability
All data generated or analyzed during this study are included in the manuscript and supporting source data file.
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Funding
Ministry of Science and Technology of the People's Republic of China (the National Key R&D Program of China, 2022YFD1400700)
- Yi-Cheng Ma
Foundation for Innovative Research Groups of the National Natural Science Foundation of China (the National Natural Science Foundation of China,U1802233)
- Cheng-Gang Zou
Yunnan Characteristic Plant Extraction Laboratory (Independent research fund,2022YKZY006)
- Cheng-Gang Zou
Foundation for Innovative Research Groups of the National Natural Science Foundation of China (the National Natural Science Foundation of China,31900420)
- Yi-Cheng Ma
Foundation for Innovative Research Groups of the National Natural Science Foundation of China (the National Natural Science Foundation of China,32260021)
- Yi-Cheng Ma
Yunnan Province of China (he Major Science and Technology Project in Yunnan Province of China, 202001BC070004)
- Cheng-Gang Zou
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Martin Sebastian Denzel, Altos Labs, United Kingdom
Version history
- Received: December 5, 2022
- Preprint posted: December 19, 2022 (view preprint)
- Accepted: November 3, 2023
- Accepted Manuscript published: November 21, 2023 (version 1)
Copyright
© 2023, Yang et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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