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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
Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources
Huang, D. W., Sherman, B. T., & Lempicki, R. A. (2009) · Nature Protocols · doi:10.1038/nprot.2008.211 · Cited by 35,890
QIIME allows analysis of high-throughput community sequencing data
Caporaso, J. G., Kuczynski, J., Stombaugh, J., Bittinger, K., Bushman, F. D., Costello, E. K., Fierer, N., Peña, A. G., Goodrich, J. K., Gordon, J. I., et al. (2010) · Nature Methods · doi:10.1038/nmeth.f.303 · Cited by 34,887
Kim, D., Pertea, G., Trapnell, C., Pimentel, H., Kelley, R., & Salzberg, S. L. (2013) · Genome Biology · doi:10.1186/gb-2013-14-4-r36 · Cited by 12,668
The microbiome and innate immunity
Thaiss, C. A., Zmora, N., Levy, M., & Elinav, E. (2016) · Nature · doi:10.1038/nature18847 · Cited by 2,012
Detecting differential usage of exons from RNA-seq data
Anders, S., Reyes, A., & Huber, W. (2012) · Genome Research · doi:10.1101/gr.133744.111 · Cited by 1,545
Minireview: Gut microbiota: The neglected endocrine organ
Clarke, G., Stilling, R. M., Kennedy, P. J., Stanton, C., Cryan, J. F., & Dinan, T. G. (2014) · Molecular Endocrinology · doi:10.1210/me.2014-1108 · Cited by 1,192
Innate Immune Homeostasis by the Homeobox Gene Caudal and Commensal-Gut Mutualism in Drosophila
Ryu, J.-H., Kim, S.-H., Lee, H.-Y., Bai, J. Y., Nam, Y., Bae, J., Lee, D. G., Shin, S. C., Ha, E.-M., & Lee, W. (2008) · Science · doi:10.1126/science.1149357 · Cited by 857
Wang, J., Thingholm, L. B., Skiecevičienė, J., Rausch, P., Kummen, M., Hov, J. R., Degenhardt, F., Heinsen, F.-A., Rühlemann, M. C., Szymczak, S., et al. (2016) · Nature Genetics · doi:10.1038/ng.3695 · Cited by 625
Self-citationChoe, K., Werner, T., Stöven, S., Hultmark, D., & Anderson, K. V. (2002) · Science · doi:10.1126/science.1070216 · Cited by 606
Greenspan, R. J., & Ferveur, J. (2000) · Annual Review of Genetics · doi:10.1146/annurev.genet.34.1.205 · Cited by 594
Gut-associated microbes of Drosophila melanogaster
Broderick, N. A., & Lemaître, B. (2012) · Gut Microbes · doi:10.4161/gmic.19896 · Cited by 583
Gut homeostasis in a microbial world: insights from Drosophila melanogaster
Buchon, N., Broderick, N. A., & Lemaître, B. (2013) · Nature Reviews Microbiology · doi:10.1038/nrmicro3074 · Cited by 515
Clark, R. I., Salazar, A., Yamada, R., Fitz-Gibbon, S., Morselli, M., Alcaraz, J., Rana, A., Rera, M., Pellegrini, M., Ja, W. W., et al. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.08.004 · Cited by 510
Microbiota-Induced Changes in Drosophila melanogaster Host Gene Expression and Gut Morphology
Broderick, N. A., Buchon, N., & Lemaître, B. (2014) · mBio · doi:10.1128/mbio.01117-14 · Cited by 431
Chen, K., Chen, Z., Wu, D., Zhang, L., Lin, X., Su, J., Rodriguez, B., Xi, Y., Xia, Z., Chen, X., et al. (2015) · Nature Genetics · doi:10.1038/ng.3385 · Cited by 373
Self-citationFOXO-dependent regulation of innate immune homeostasis
Becker, T., Loch, G., Beyer, M., Zinke, I., Aschenbrenner, A. C., Carrera, P., Inhester, T., Schultze, J. L., & Hoch, M. (2010) · Nature · doi:10.1038/nature08698 · Cited by 357
Gut microbiota dictates the metabolic response ofDrosophilato diet
Wong, A. C.-N., Dobson, A. J., & Douglas, A. E. (2014) · Journal of Experimental Biology · doi:10.1242/jeb.101725 · Cited by 311
Altered brain-gut axis in autism: comorbidity or causative mechanisms
Mayer, E. A., Padua, D., & Tillisch, K. (2014) · BioEssays · doi:10.1002/bies.201400075 · Cited by 304
Secombe, J., Li, L., Carlos, L. S., & Eisenman, R. N. (2007) · Genes & Development · doi:10.1101/gad.1523007 · Cited by 285
Self-citationIntestinal microbial dysbiosis aggravates the progression of Alzheimer’s disease in Drosophila
Wu, S.-C., Cao, Z.-S., Chang, K.-M., & Juang, J. (2017) · Nature Communications · doi:10.1038/s41467-017-00040-6 · Cited by 261
Bosco-Drayon, V., Poidevin, M., Boneca, I. G., Narbonne-Reveau, K., Royet, J., & Charroux, B. (2012) · Cell Host & Microbe · doi:10.1016/j.chom.2012.06.002 · Cited by 255
NF- B in the Immune Response of DrosophilaPreprint
Hétru, C., & Hoffmann, J. A. (2009) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a000232 · Cited by 252
Cognitive decline, dietary factors and gut–brain interactions
Caracciolo, B., Xu, W., Collins, S. M., & Fratiglioni, L. (2013) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2013.11.011 · Cited by 213
Redox signaling mediated by the gut microbiota
Jones, R. M., & Neish, A. S. (2016) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.10.495 · Cited by 210
Quantifying the contribution of recessive coding variation to developmental disorders
Martin, H. C., Jones, W. D., McIntyre, R., Sanchez-Andrade, G., Sanderson, M., Stephenson, J. D., Jones, C. P., Handsaker, J., Gallone, G., Bruntraeger, M., et al. (2018) · Science · doi:10.1126/science.aar6731 · Cited by 201
Ecdysone triggered PGRP‐LC expression controls Drosophila innate immunity
Rus, F., Flatt, T., Tong, M., Aggarwal, K., Okuda, K., Kleino, A., Yates, E., Tatar, M., & Silverman, N. S. (2013) · The EMBO Journal · doi:10.1038/emboj.2013.100 · Cited by 176
Koemans, T. S., Kleefstra, T., Chubak, M. C., Stone, M. H., Reijnders, M. R. F., de Munnik, S., Willemsen, M. H., Fencková, M., Schrander-Stumpel, C. T. R. M., Bok, L. A., et al. (2017) · PLoS Genetics · doi:10.1371/journal.pgen.1006864 · Cited by 167
Behavioral, physical, and demographic changes in Drosophila populations through dietary restriction
Bross, T. G., Rogina, B., & Helfand, S. L. (2005) · Aging Cell · doi:10.1111/j.1474-9726.2005.00181.x · Cited by 166
Speciation by Symbiosis: the Microbiome and Behavior
Shropshire, J. D., & Bordenstein, S. R. (2016) · mBio · doi:10.1128/mbio.01785-15 · Cited by 152
Tynkkynen, S. (1998) · International Journal of Food Microbiology · doi:10.1016/s0168-1605(98)00051-8 · Cited by 149
Coordination of legs during straight walking and turning in Drosophila melanogaster
Strau�, R., & Heisenberg, M. (1990) · Journal of Comparative Physiology A · doi:10.1007/bf00192575 · Cited by 146
Nutrient-Dependent Impact of Microbes onDrosophila suzukiiDevelopment
Bing, X., Gerlach, J., Loeb, G. M., & Buchon, N. (2018) · mBio · doi:10.1128/mbio.02199-17 · Cited by 142
Influence of early life exposure, host genetics and diet on the mouse gut microbiome and metabolome
Snijders, A. M., Langley, S. A., Kim, Y., Brislawn, C., Noecker, C. A., Zink, E., Fansler, S. J., Casey, C., Miller, D. R., Huang, Y., et al. (2016) · Nature Microbiology · doi:10.1038/nmicrobiol.2016.221 · Cited by 133
Self-citationIwase, S., Brookes, E., Agarwal, S., Badeaux, A. I., Ito, H., Vallianatos, C. N., Tomassy, G. S., Kasza, T., Lin, G. R., Thompson, A., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2015.12.091 · Cited by 132
Social attraction mediated by fruit flies' microbiome
Venu, I., Durisko, Z., Xu, J., & Dukas, R. (2014) · Journal of Experimental Biology · doi:10.1242/jeb.099648 · Cited by 120
Scandaglia, M., López‐Atalaya, J. P., Medrano-Fernandez, A., López-Cascales, M. T., del Blanco, B., Lipiński, M., Benito, E., Olivares, R., Iwase, S., Shi, Y., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.09.014 · Cited by 120
Qian, Y., Cao, Y., Deng, B., Yang, G., Li, J., Xu, R., Zhang, D., Huang, J., & Rao, Y. (2017) · eLife · doi:10.7554/elife.26519 · Cited by 104
Self-citationAsong, J., Wolfert, M. A., Maiti, K. K., Miller, D. K., & Boons, G. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m806633200 · Cited by 103
Liu, X., & Secombe, J. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.11.007 · Cited by 101
Self-citationRett Syndrome: A Focus on Gut Microbiota
Borghi, E., Borgo, F., Severgnini, M., Savini, M. N., Casiraghi, M. C., & Vignoli, A. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18020344 · Cited by 90
Brookes, E., Laurent, B., Õunap, K., Carroll, R., Moeschler, J. B., Field, M. J., Schwartz, C. E., Gécz, J., & Shi, Y. (2015) · Human Molecular Genetics · doi:10.1093/hmg/ddv046 · Cited by 88
Ptaschinski, C., Mukherjee, S., Moore, M. L., Albert, M., Helin, K., Kunkel, S. L., & Lukacs, N. W. (2015) · PLoS Pathogens · doi:10.1371/journal.ppat.1004978 · Cited by 84
Navarro‐Costa, P., McCarthy, A., Prudêncio, P., Greer, C., Guilgur, L. G., Becker, J. D., Secombe, J., Rangan, P., & Martinho, R. G. (2016) · Nature Communications · doi:10.1038/ncomms12331 · Cited by 71
Self-citationHan, G., Lee, H., Jeong, S. E., Jeon, C. O., & Hyun, S. (2017) · Microbial Ecology · doi:10.1007/s00248-016-0925-3 · Cited by 69
Zhai, Z., Huang, X., & Yin, Y. (2017) · Developmental & Comparative Immunology · doi:10.1016/j.dci.2017.11.008 · Cited by 67
Drosophila as a model for intestinal dysbiosis and chronic inflammatory diseases
Lee, K., & Lee, W. (2013) · Developmental & Comparative Immunology · doi:10.1016/j.dci.2013.05.005 · Cited by 64
The neurogenetics of group behavior inDrosophila melanogaster
Ramdya, P. P., Schneider, J., & Levine, J. D. (2017) · Journal of Experimental Biology · doi:10.1242/jeb.141457 · Cited by 63
KDM5 Interacts with Foxo to Modulate Cellular Levels of Oxidative Stress
Liu, X., Greer, C., & Secombe, J. (2014) · PLoS Genetics · doi:10.1371/journal.pgen.1004676 · Cited by 62
Self-citationChen, R., Davis, L. K., Guter, S. J., Wei, Q., Jacob, S., Potter, M. H., Cox, N. J., Cook, E. H., Sutcliffe, J. S., & Li, B. (2017) · Molecular Autism · doi:10.1186/s13229-017-0130-3 · Cited by 59
A Drosophila Model of Intellectual Disability Caused by Mutations in the Histone Demethylase KDM5
Zamurrad, S., Hatch, H. A. M., Drelon, C., Belálcazar, H. M., & Secombe, J. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.02.018 · Cited by 55
Self-citationWise, A., Tenezaca, L., Fernandez, R. W., Schatoff, E. M., Flores, J., Ueda, A., Zhong, X., Wu, C., Simon, A. F., & Venkatesh, T. (2015) · Journal of Neurogenetics · doi:10.3109/01677063.2015.1064916 · Cited by 54
The regulatory isoform rPGRP-LC induces immune resolution via endosomal degradation of receptors
Neyen, C. D., Runchel, C., Schüpfer, F., Meier, P., & Lemaître, B. (2016) · Nature Immunology · doi:10.1038/ni.3536 · Cited by 51
Fukuyama, H., Verdier, Y., Guan, Y., Makino‐Okamura, C., Shilova, V. Y., Liu, X., Maksoud, É., Matsubayashi, J., Haddad, I., Spirohn, K., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1304380110 · Cited by 45
Self-citationIyengar, A. S. R., Imoehl, J., Ueda, A., Nirschl, J., & Wu, C. (2012) · Journal of Neurogenetics · doi:10.3109/01677063.2012.729626 · Cited by 44
Fieremans, N., Esch, H. V., de Ravel, T. J. L., Driessche, J. V., Belet, S., Bauters, M., & Froyen, G. (2015) · European Journal of Medical Genetics · doi:10.1016/j.ejmg.2015.03.003 · Cited by 33
The Histone Demethylase KDM5 Is Essential for Larval Growth in Drosophila
Drelon, C., Belálcazar, H. M., & Secombe, J. (2018) · Genetics · doi:10.1534/genetics.118.301004 · Cited by 31
Self-citationUsing Animal Models to Study the Role of the Gut–Brain Axis in Autism
Nithianantharajah, J., Balasuriya, G. K., Franks, A. E., & Hill‐Yardin, E. L. (2017) · Current Developmental Disorders Reports · doi:10.1007/s40474-017-0111-4 · Cited by 29
Conditions Affecting Social Space in Drosophila melanogaster
McNeil, A. R., Jolley, S. N., Akinleye, A. A., Nurilov, M., Rouzyi, Z., Milunovich, A. J., Chambers, M. C., & Simon, A. F. (2015) · Journal of Visualized Experiments · doi:10.3791/53242 · Cited by 26
Wei, G., Deng, X., Agarwal, S., Iwase, S., Distèche, C. M., & Xu, J. (2016) · Journal of Molecular Neuroscience · doi:10.1007/s12031-016-0770-3 · Cited by 25
Kenmoku, H., Ishikawa, H., Oté, M., Kuraishi, T., & Kurata, S. (2016) · Journal of Experimental Biology · doi:10.1242/jeb.122960 · Cited by 21
Inducing RNAi in Drosophila Cells by Transfection with dsRNAPreprint
Zhou, R., Mohr, S. E., Hannon, G. J., & Perrimon, N. (2013) · Cold Spring Harbor Protocols · doi:10.1101/pdb.prot074351 · Cited by 21
Towards understanding the genetics of Autism
Ouhtit, A. (2016) · Frontiers in Bioscience-Elite · doi:10.2741/776 · Cited by 17
Straightforward Assay for Quantification of Social Avoidance in Drosophila melanogaster
Fernandez, R. W., Nurilov, M., Feliciano, O., McDonald, I. S., & Simon, A. F. (2014) · Journal of Visualized Experiments · doi:10.3791/52011 · Cited by 13
Johanna, S., Willi, M., Schoberleitner, I., Krogsdam, A., Orth‐Höller, D., Trajanoski, Z., & Lusser, A. (2016) · PLoS ONE · doi:10.1371/journal.pone.0153476 · Cited by 12
Methods to Assess Intestinal Stem Cell Activity in Response to Microbes in Drosophila melanogaster
Houtz, P., & Buchon, N. S. (2014) · Methods in molecular biology · doi:10.1007/978-1-4939-1453-1_14 · Cited by 6
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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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