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Drosophila Histone Demethylase KDM5 Regulates Social Behavior through Immune Control and Gut Microbiota Maintenance
Open accessAbstract
Loss-of-function mutations in the histone demethylases KDM5A, KDM5B, or KDM5C are found in intellectual disability (ID) and autism spectrum disorders (ASD) patients. Here, we use the model organism Drosophila melanogaster to delineate how KDM5 contributes to ID and ASD. We show that reducing KDM5 causes intestinal barrier dysfunction and changes in social behavior that correlates with compositional changes in the gut microbiota. Therapeutic alteration of the dysbiotic microbiota through antibiotic administration or feeding with a probiotic Lactobacillus strain partially rescues the behavioral, lifespan, and cellular phenotypes observed in kdm5-deficient flies. Mechanistically, KDM5 was found to transcriptionally regulate component genes of the immune deficiency (IMD) signaling pathway and subsequent maintenance of host-commensal bacteria homeostasis in a demethylase-dependent manner. Together, our study uses a genetic approach to dissect the role of KDM5 in the gut-microbiome-brain axis and suggests that modifying the gut microbiome may provide therapeutic benefits for ID and ASD patients.
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“the gut microbiota has been shown to modulate locomotor activity in Drosophila, probably via bacterial-derived metabolites (Schretter et al., 2018), (Chen et al., 2019).”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Chen et al., 2019
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Cites
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Cryan, J. F., O'Riordan, K. J., Cowan, C. S. M., Sandhu, K. V., Bastiaanssen, T. F. S., Boehme, M., Codagnone, M. G., Cussotto, S., Fulling, C., Golubeva, A. V., et al. (2019) · Physiological Reviews · doi:10.1152/physrev.00018.2018 · Cited by 5,286
Microbiota in health and diseases
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Self-citationShort chain fatty acids: Microbial metabolites for gut-brain axis signalling
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Metadata
- Authors
- Chen, K., Luan, X., Liu, Q., Wang, J., Chang, X., Snijders, A. M., Mao, J.-H., Secombe, J., Dan, Z., Chen, J.-H., Wang, Z., Dong, X., Qiu, C., Chang, X., Zhang, D., Celniker, S. E., & Liu, X.
- Affiliations
- Second Affiliated Hospital of Nanjing Medical University (CN)
- State Key Laboratory of Reproductive Medicine (CN)
- Lawrence Berkeley National Laboratory (US)
- Albert Einstein College of Medicine (US)
- Jiangnan University (CN)
- Nanjing Medical University (CN)
- Corresponding author
- Liu, Xingyin
- ORCID
- Venue
- Cell Host & Microbe
- Publisher
- Elsevier BV
- Published
- 2019-04
- Volume
- 25
- Issue
- 4
- Pages
- 537-552.e8
- ISSN
- 1931-3128 (ISSN-L)
- PMC
- PMC6749836
- OpenAlex
- W2924425749
- Cited by
- 208
- References
- 65
- Citations by year
- 2026: 18 · 2025: 27 · 2024: 34 · 2023: 37 · 2022: 37 · 2021: 35 · 2020: 14 · 2019: 6
- FWCI
- 10.99
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Host & Microbe (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
- Funders
- Lawrence Berkeley National Laboratory
- Laboratory Directed Research and Development (DE AC02-05CH11231, M2B)
- National Natural Science Foundation of China (81671983, 81871628)
- National Institutes of Health (31671311, R01GM112783)
- Qinglan Project of Jiangsu Province of China
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- KDM5, histone demethylase, social behavior, intellectual disability, autism spectrum disorder, gut microbiota, intestinal barrier dysfunction, probiotics, Lactobacillus, lifespan, Drosophila melanogaster
- MeSH terms
- Autism Spectrum Disorder, Gastrointestinal Microbiome, Animals, Behavior, Animal, Disease Models, Animal, Drosophila, Drosophila melanogaster, Female, Humans, Intestinal Mucosa, Male, Social Behavior, Drosophila Proteins, Histone Demethylases
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