The DOI matches its Crossref record; 50 of the 50 references it cites were found in a registry or an index.
Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells
Abstract
Gut commensal microbes shape the mucosal immune system by regulating the differentiation and expansion of several types of T cell. Clostridia, a dominant class of commensal microbe, can induce colonic regulatory T (Treg) cells, which have a central role in the suppression of inflammatory and allergic responses. However, the molecular mechanisms by which commensal microbes induce colonic Treg cells have been unclear. Here we show that a large bowel microbial fermentation product, butyrate, induces the differentiation of colonic Treg cells in mice. A comparative NMR-based metabolome analysis suggests that the luminal concentrations of short-chain fatty acids positively correlates with the number of Treg cells in the colon. Among short-chain fatty acids, butyrate induced the differentiation of Treg cells in vitro and in vivo, and ameliorated the development of colitis induced by adoptive transfer of CD4(+) CD45RB(hi) T cells in Rag1(-/-) mice. Treatment of naive T cells under the Treg-cell-polarizing conditions with butyrate enhanced histone H3 acetylation in the promoter and conserved non-coding sequence regions of the Foxp3 locus, suggesting a possible mechanism for how microbial-derived butyrate regulates the differentiation of Treg cells. Our findings provide new insight into the mechanisms by which host-microbe interactions establish immunological homeostasis in the gut.
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In the citing paper
“For instance, butyrate has been shown to restrict inflammation by promoting the differentiation of Treg cells and supporting the functions of regulatory B cells.706–708”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [708]
In the citing paper
“These were shown to promote the expansion of Tregs, but they also seem to improve the function of effector T cells10–15.”
From Microbial short-chain fatty acids modulate CD8+ T cell responses and improve adoptive immunotherapy for cancer (2021) · cites this paper as [12]
In the citing paper
“Commensal-derived butyrate was shown to induce epigenetic reprogramming of Tregs by enhancing the acetylation of histone H3 in the promoter and conserved non-coding sequence regions of the Foxp3 locus12.”
From Microbial short-chain fatty acids modulate CD8+ T cell responses and improve adoptive immunotherapy for cancer (2021) · cites this paper as [12]
In the citing paper
“In addition, both propionate and butyrate could act as histone deacetylase (HDAC) inhibitor [74–76], through which SCFA increased histone acetylation in the promoter and conserved non-coding sequence (CNS) regions of the Foxp3 locus, the master transcription factor and specific marker of suppressive Tregs [75].”
From Gut microbiota-mediated immunomodulation in tumor (2021) · cites this paper as [75]
In the citing paper
“Butyrate plays a crucial role in regulating anti-inflammatory responses by controlling the expression of forkhead box protein P3 (Foxp3), essential for suppressing excessive inflammation [57].”
From The Gut–Brain–Microbiota Connection and Its Role in Autism Spectrum Disorders (2025) · cites this paper as [57]
In the citing paper
“Conversely, the de novo differentiation of cTregs relies on HDAC inhibition in both DCs and T cells, which acetate does not promote (Arpaia et al., 2013; Furusawa et al., 2013).”
From Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System (2017) · cites this paper as Furusawa et al., 2013
In the citing paper
“whereas propionate and butyrate, but not acetate, increase the de novo differentiation of naive T cells into Tregs (Arpaia et al., 2013; Furusawa et al., 2013; Singh et al., 2014; Smith et al., 2013).”
From Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System (2017) · cites this paper as Furusawa et al., 2013
In the citing paper
“acetate and propionate, but not butyrate, stimulate the expansion of pre-existing colonic Tregs (cTregs)”
From Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System (2017) · cites this paper as Furusawa et al., 2013
In the citing paper
“oral administration of SCFAs protected mice from T cell-induced colitis by inducing immunosuppressive Tregs [38-40].”
From Antibiotic-Induced Changes in the Intestinal Microbiota and Disease (2016) · cites this paper as [39]
In the citing paper
“and on DCs, conferring a higher capacity to drive naïve T cell differentiation into Tregs [38-40].”
From Antibiotic-Induced Changes in the Intestinal Microbiota and Disease (2016) · cites this paper as [39]
In the citing paper
“SCFAs were present at reduced concentrations in the fecal pellets of GF or antibiotic-treated mice”
From Antibiotic-Induced Changes in the Intestinal Microbiota and Disease (2016) · cites this paper as [39]
In the citing paper
“SCFAs were found to act directly on T cells via the receptor GPCR43, thus enhancing FoxP3 expression through DNA acetylation”
From Antibiotic-Induced Changes in the Intestinal Microbiota and Disease (2016) · cites this paper as [39]
In the citing paper
“three different laboratories have identified microbiota-derived SCFAs (particularly propionate and butyrate), to be responsible for Treg differentiation/accumulation [38-40].”
From Antibiotic-Induced Changes in the Intestinal Microbiota and Disease (2016) · cites this paper as [39]
In the citing paper
“These receptors, which play crucial roles in host-microbiota interactions, are expressed at various levels in different cell types such as IECs, innate lymphoid cells, macrophages, T cells, and dendritic cells.184”
From Regulation of Intestinal Barrier Function by Microbial Metabolites (2021) · cites this paper as [184]
In the citing paper
“The pathophysiological consequences of this condition are predictable (epithelial cell death and dysregulated inflammation), but the clinical consequences are unknown.”
From The microbiome and critical illness (2016) · cites this paper as [76]
In the citing paper
“Treg cells are induced by a variety of bacterial groups67,68 and by the SCFA butyrate47, which is produced by bacterial fermentation.”
From The gut microbiota and the brain–gut–kidney axis in hypertension and chronic kidney disease (2018) · cites this paper as [47]
Citations
Cites
Clustal W and Clustal X version 2.0
Larkin, M., Blackshields, G., Brown, N. P., Chenna, R., McGettigan, P., McWilliam, H., Valentin, F., Wallace, I. M., Wilm, A., López, R., et al. (2007) · Bioinformatics · doi:10.1093/bioinformatics/btm404 · Cited by 28,598
Frank, D. N., St. Amand, A. L., Feldman, R. A., Boedeker, E. C., Harpaz, N., & Pace, N. R. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0706625104 · Cited by 4,611
Induction of Intestinal Th17 Cells by Segmented Filamentous Bacteria
Ivanov, I. I., Atarashi, K., Manel, N., Brodie, E. L., Shima, T., Karaoz, U., Wei, D., Goldfarb, K. C., Santee, C. A., Lynch, S. V., et al. (2009) · Cell · doi:10.1016/j.cell.2009.09.033 · Cited by 4,554
Self-citationRecognition of Commensal Microflora by Toll-Like Receptors Is Required for Intestinal Homeostasis
Rakoff-Nahoum, S., Paglino, J., Eslami-Varzaneh, F., Edberg, S., & Medzhitov, R. (2004) · Cell · doi:10.1016/j.cell.2004.07.002 · Cited by 4,251
Induction of Colonic Regulatory T Cells by Indigenous Clostridium Species
Atarashi, K., Tanoue, T., Shima, T., Imaoka, A., Kuwahara, T., Momose, Y., Cheng, G., Yamasaki, S., Saito, T., Ohba, Y., et al. (2011) · Science · doi:10.1126/science.1198469 · Cited by 3,752
Self-citationInteractive Tree Of Life (iTOL): an online tool for phylogenetic tree display and annotation
Letunić, I., & Bork, P. (2006) · Bioinformatics · doi:10.1093/bioinformatics/btl529 · Cited by 3,334
Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43
Maslowski, K. M., Vieira, A. T., Ng, A., Kranich, J., Sierro, F., Yu, D., Schilter, H. C., Rolph, M. S., Mackay, F., Artis, D., et al. (2009) · Nature · doi:10.1038/nature08530 · Cited by 3,241
Regulatory T cells: mechanisms of differentiation and function
Josefowicz, S. Z., Lu, L.-F., & Rudensky, A. Y. (2012) · Annual Review of Immunology · doi:10.1146/annurev.immunol.25.022106.141623 · Cited by 2,866
Brown, A. J., Goldsworthy, S. M., Barnes, A. A., Eilert, M. M., Tcheang, L., Daniels, D., Muir, A. I., Wigglesworth, M. J., Kinghorn, I., Fraser, N. J., et al. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m211609200 · Cited by 2,409
Bifidobacteria can protect from enteropathogenic infection through production of acetate
Fukuda, S., Toh, H., Hase, K., Oshima, K., Nakanishi, Y., Yoshimura, K., Tobe, T., Clarke, J. M., Topping, D. L., Suzuki, T., et al. (2011) · Nature · doi:10.1038/nature09646 · Cited by 2,387
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Liu, L., Li, Q., Yang, Y., & Guo, A. (2021) · Frontiers in Veterinary Science · doi:10.3389/fvets.2021.736739 · Cited by 356
Zhang, Y., Tu, S., Ji, X., Wu, J., Meng, J., Gao, J., Shao, X., Shi, S., Gan, W., Qiu, J., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-45636-x · Cited by 338
Finding the Missing Links among Metabolites, Microbes, and the Host
Dorrestein, P. C., Mazmanian, S. K., & Knight, R. (2014) · Immunity · doi:10.1016/j.immuni.2014.05.015 · Cited by 317
Microbiome therapeutics — Advances and challenges
Mimee, M., Citorik, R. J., & Lu, T. K. (2016) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2016.04.032 · Cited by 324
Tahara, Y., Yamazaki, M., Sukigara, H., Motohashi, H., Sasaki, H., Miyakawa, H., Haraguchi, A., Ikeda, Y., Fukuda, S., & Shibata, S. (2018) · Scientific Reports · doi:10.1038/s41598-018-19836-7 · Cited by 317
Self-citationPotential Role of the Microbiome in Acne: A Comprehensive Review
Lee, Y. B., Byun, E. J., & Kim, H. S. (2019) · Journal of Clinical Medicine · doi:10.3390/jcm8070987 · Cited by 339
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Lobionda, S., Sittipo, P., Kwon, H. Y., & Lee, Y. K. (2019) · Microorganisms · doi:10.3390/microorganisms7080271 · Cited by 326
Uribe-Herranz, M., Rafail, S., Beghi, S., Gil-de-Gómez, L., Verginadis, I., Bittinger, K., Pustylnikov, S., Pierini, S., Perales-Linares, R., Blair, I. A., et al. (2019) · Journal of Clinical Investigation · doi:10.1172/jci124332 · Cited by 316
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D’Amelio, P., & Sassi, F. (2018) · Calcified Tissue International · doi:10.1007/s00223-017-0331-y · Cited by 315
Immune-microbiota interactions in health and disease
Palm, N. W., de Zoete, M. R., & Flavell, R. A. (2015) · Clinical Immunology · doi:10.1016/j.clim.2015.05.014 · Cited by 315
Modulation of immune development and function by intestinal microbiota
Kabat, A. M., Srinivasan, N., & Maloy, K. J. (2014) · Trends in Immunology · doi:10.1016/j.it.2014.07.010 · Cited by 320
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Shono, Y., & van den Brink, M. R. M. (2018) · Nature reviews. Cancer · doi:10.1038/nrc.2018.10 · Cited by 320
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Zhang, H., Liao, X., Sparks, J. B., & Luo, X. (2014) · Applied and Environmental Microbiology · doi:10.1128/aem.02676-14 · Cited by 308
Morris, G., Berk, M., Carvalho, A. F., Caso, J. R., Sanz, Y., Walder, K. R., & Maes, M. H. J. (2016) · Molecular Neurobiology · doi:10.1007/s12035-016-0004-2 · Cited by 318
Burrello, C., Garavaglia, F., Cribiù, F. M., Ercoli, G., Lopez, G., Troisi, J., Colucci, A., Guglietta, S., Carloni, S., Guglielmetti, S., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-07359-8 · Cited by 315
Target intestinal microbiota to alleviate disease progression in amyotrophic lateral sclerosis
Zhang, Y.-G., Wu, S., Yi, J., Xia, Y., Jin, D., Zhou, J., & Sun, J. (2017) · Clinical Therapeutics · doi:10.1016/j.clinthera.2016.12.014 · Cited by 287
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Role of dietary fiber in the recovery of the human gut microbiome and its metabolome
Tanes, C., Bittinger, K. L., Gao, Y., Friedman, E. S., Nessel, L. A., Paladhi, U. R., Chau, L., Panfen, E., Fischbach, M. A., Braun, J. G., et al. (2021) · Cell Host & Microbe · doi:10.1016/j.chom.2020.12.012 · Cited by 325
Mining the microbiota for microbial and metabolite-based immunotherapies
Skelly, A. N., Sato, Y., Kearney, S., & Honda, K. (2019) · Nature Reviews Immunology · doi:10.1038/s41577-019-0144-5 · Cited by 306
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Li, W., Hang, S., Fang, Y., Bae, S., Zhang, Y., Zhang, M., Wang, G., McCurry, M. D., Bae, M., Paik, D., et al. (2021) · Cell Host & Microbe · doi:10.1016/j.chom.2021.07.013 · Cited by 306
Metabolite-Sensing G Protein–Coupled Receptors—Facilitators of Diet-Related Immune Regulation
Tan, J. K., McKenzie, C. I., Mariño, E., Macia, L., & Mackay, C. R. (2017) · Annual Review of Immunology · doi:10.1146/annurev-immunol-051116-052235 · Cited by 305
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Moser, T., Akgün, K., Proschmann, U., Sellner, J., & Ziemssen, T. (2020) · Autoimmunity Reviews · doi:10.1016/j.autrev.2020.102647 · Cited by 319
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Theriot, C. M., & Young, V. B. (2015) · Annual Review of Microbiology · doi:10.1146/annurev-micro-091014-104115 · Cited by 320
Ihara, S., Hirata, Y., & Koike, K. (2017) · Journal of Gastroenterology · doi:10.1007/s00535-017-1350-1 · Cited by 313
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Zhou, C., Zhou, Y., & Fang, J. (2021) · Trends in cancer · doi:10.1016/j.trecan.2021.01.010 · Cited by 313
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Al Nabhani, Z., & Eberl, G. (2020) · Mucosal Immunology · doi:10.1038/s41385-020-0257-y · Cited by 301
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Ansaldo, E., Farley, T. K., & Belkaid, Y. (2021) · Annual Review of Immunology · doi:10.1146/annurev-immunol-093019-112348 · Cited by 312
Gaudino, S. J., & Kumar, P. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00360 · Cited by 323
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Wang, G., Huang, S., Wang, Y., Cai, S., Yu, H., Liu, H., Zeng, X., Zhang, G., & Qiao, S. (2019) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-019-03190-6 · Cited by 305
Chakaroun, R., Massier, L., & Kovacs, P. L. (2020) · Nutrients · doi:10.3390/nu12041082 · Cited by 307
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Kespohl, M., Vachharajani, N., Luu, M., Harb, H., Pautz, S., Wolff, S., Sillner, N., Walker, A., Schmitt-Kopplin, P., Boettger, T., et al. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01036 · Cited by 294
The group 2 innate lymphoid cell ( ILC 2) regulatory network and its underlying mechanisms
Kabata, H., Moro, K., & Koyasu, S. (2018) · Immunological Reviews · doi:10.1111/imr.12706 · Cited by 295
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Farré, R., Fiorani, M., Abdurahiman, S., & Matteoli, G. (2020) · Nutrients · doi:10.3390/nu12041185 · Cited by 317
Kim, S., Shin, Y.-C., Kim, T., Kim, Y., Lee, Y., Lee, S.-H., Kim, M., Eunju, O., Kim, K. S., & Kweon, M. (2021) · Gut Microbes · doi:10.1080/19490976.2021.1892441 · Cited by 303
Sun, J., Furio, L., Mecheri, R., van der Does, A. M., Lundeberg, E., Saveanu, L., Chen, Y., van Endert, P., Agerberth, B., & Diana, J. (2015) · Immunity · doi:10.1016/j.immuni.2015.07.013 · Cited by 292
Food, immunity, and the microbiome
Tilg, H., & Moschen, A. R. (2015) · Gastroenterology · doi:10.1053/j.gastro.2014.12.036 · Cited by 292
Minter, M. R., Hinterleitner, R., Meisel, M., Zhang, C., Leone, V., Zhang, X., Oyler-Castrillo, P., Zhang, X., Musch, M. W., Shen, X., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-11047-w · Cited by 292
Miranda, P. M., Palma, G. D., Serkis, V., Lu, J., Louis-Auguste, M., McCarville, J. L., Verdu, E. F., Collins, S. M., & Berčík, P. (2018) · Microbiome · doi:10.1186/s40168-018-0433-4 · Cited by 302
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An integrative view of microbiome-host interactions in inflammatory bowel diseases
Wlodarska, M., Kostic, A. D., & Xavier, R. J. (2015) · Cell Host & Microbe · doi:10.1016/j.chom.2015.04.008 · Cited by 287
Liu, X., Zhang, Y., Li, W., Zhang, B., Yin, J., Liuqi, S., Wang, J., Peng, B., & Wang, S. (2022) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.2c06417 · Cited by 289
Unique aspects of the perinatal immune system
Zhang, X., Zhivaki, D., & Lo-Man, R. (2017) · Nature Reviews Immunology · doi:10.1038/nri.2017.54 · Cited by 276
Epigenetics and Allergy: from Basic Mechanisms to Clinical Applications
Potaczek, D. P., Harb, H., Michel, S., Alhamwe, B. A., Renz, H. E., & Tost, J. (2017) · Epigenomics · doi:10.2217/epi-2016-0162 · Cited by 286
Lipid metabolism in T cell signaling and function
Lim, S. A., Su, W., Chapman, N. M., & Chi, H. (2022) · Nature Chemical Biology · doi:10.1038/s41589-022-01017-3 · Cited by 295
The impacts of natural polysaccharides on intestinal microbiota and immune responses – a review
Tang, C., Ding, R., Sun, J. G., Liu, J., Kan, J., & Jin, C. (2019) · Food & Function · doi:10.1039/c8fo01946k · Cited by 284
Dohlman, A. B., Mendoza, D. A., Ding, S., Gao, M. C., Dressman, H. K., Iliev, I. D., Lipkin, S. M., & Shen, X. (2021) · Cell Host & Microbe · doi:10.1016/j.chom.2020.12.001 · Cited by 287
Obata, Y., & Pachnis, V. (2016) · Gastroenterology · doi:10.1053/j.gastro.2016.07.044 · Cited by 286
Self-citationEvaluating Causality of Gut Microbiota in Obesity and Diabetes in Humans
Meijnikman, A. S., Gerdes, V. E. A., Nieuwdorp, M., & Herrema, H. (2017) · Endocrine Reviews · doi:10.1210/er.2017-00192 · Cited by 283
Tissue-resident memory T cells at the center of immunity to solid tumors
Amsen, D., van Gisbergen, K. P. J. M., Hombrink, P., & van Lier, R. A. W. (2018) · Nature Immunology · doi:10.1038/s41590-018-0114-2 · Cited by 291
Co-evolution and Co-speciation of Host-Gut Bacteria Systems
Groussin, M., Mazel, F., & Alm, E. J. (2020) · Cell Host & Microbe · doi:10.1016/j.chom.2020.06.013 · Cited by 292
Mao, J., Wang, D., Long, J., Xu, Y., Lin, J., Song, Y., Xie, F., Xun, Z., Wang, Y., Wang, Y., et al. (2021) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2021-003334 · Cited by 285
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Cheng, J., Hu, J., Geng, F., & Nie, S. (2022) · Food Science and Human Wellness · doi:10.1016/j.fshw.2022.04.002 · Cited by 291
Kang, C., Wang, B., Kaliannan, K., Wang, X., Lang, H., Hui, S., Huang, L., Zhang, Y., Zhou, M., Chen, M., et al. (2017) · mBio · doi:10.1128/mbio.00470-17 · Cited by 279
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Miyamoto, J., Mizukure, T., Park, S.-B., Kishino, S., Kimura, I., Hirano, K., Bergamo, P., Rossi, M., Suzuki, T., Arita, M., et al. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.610733 · Cited by 272
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The microbiome in inflammatory bowel diseases: from pathogenesis to therapy
Liu, S., Zhao, W., Lan, P., & Mou, X. (2020) · Protein & Cell · doi:10.1007/s13238-020-00745-3 · Cited by 279
Kamo, T., Akazawa, H., Suda, W., Saga-Kamo, A., Shimizu, Y., Yagi, H., Liu, Q., Nomura, S., Naito, A. T., Takeda, N., et al. (2017) · PLoS ONE · doi:10.1371/journal.pone.0174099 · Cited by 268
Self-citationVemuri, R., Sylvia, K. E., Klein, S. L., Forster, S. C., Plebanski, M., Eri, R., & Flanagan, K. L. (2019) · Seminars in Immunopathology · doi:10.1007/s00281-018-0716-7 · Cited by 265
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Frati, F., Salvatori, C., Incorvaia, C., Bellucci, A., Cara, G. D., Marcucci, F., & Esposito, S. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms20010123 · Cited by 274
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Zhang, S., Gang, X., Yang, S., Cui, M., Sun, L., Li, Z., & Wang, G. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.678355 · Cited by 263
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Sharma, A., & Rudra, D. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00883 · Cited by 273
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Huang, T., Lai, J., Du, Y., Xu, Y., Ruan, L., & Hu, S. (2019) · Frontiers in Genetics · doi:10.3389/fgene.2019.00098 · Cited by 276
Recharla, N., Geesala, R., & Shi, X.-Z. P. (2023) · Nutrients · doi:10.3390/nu15102275 · Cited by 286
Tordesillas, L., & Berin, M. C. (2018) · Clinical Reviews in Allergy & Immunology · doi:10.1007/s12016-018-8680-5 · Cited by 276
Antibiotics in early life: dysbiosis and the damage done
Neuman, H., Forsythe, P., Uzan-Yulzari, A., Avni, O., & Koren, O. (2018) · FEMS Microbiology Reviews · doi:10.1093/femsre/fuy018 · Cited by 271
Regulatory immune cells in regulation of intestinal inflammatory response to microbiota
Sun, M., He, C. H., Cong, Y., & Liu, Z. (2015) · Mucosal Immunology · doi:10.1038/mi.2015.49 · Cited by 263
Commensal-pathogen interactions in the intestinal tract
Reynolds, L. A., Smith, K. A., Filbey, K. J., Harcus, Y. M., Hewitson, J. P., Redpath, S. A., Valdez, Y., Yebra, M. J., Finlay, B. B., & Maizels, R. M. (2014) · Gut Microbes · doi:10.4161/gmic.32155 · Cited by 265
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Rahman, M. M., Islam, F., Harun-Or-Rashid, M., Mamun, A. A., Rahaman, M. S., Islam, M. M., Meem, A. F. K., Sutradhar, P. R., Mitra, S., Mimi, A. A., et al. (2022) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2022.903570 · Cited by 272
Andoh, A., Nishida, A., Takahashi, K., Inatomi, O., Imaeda, H., Bamba, S., Kito, K., Sugimoto, M., & Kobayashi, T. (2016) · Journal of Clinical Biochemistry and Nutrition · doi:10.3164/jcbn.15-152 · Cited by 263
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Renz, H. E., & Skevaki, C. L. (2020) · Nature reviews. Immunology · doi:10.1038/s41577-020-00420-y · Cited by 266
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O’Sullivan, D., & Pearce, E. L. (2015) · Trends in Immunology · doi:10.1016/j.it.2014.12.004 · Cited by 261
Nylund, L., Nermes, M., Isolauri, E., Salminen, S., de Vos, W. M., & Satokari, R. M. (2014) · Allergy · doi:10.1111/all.12549 · Cited by 257
Sung, J., Kim, S., Cabatbat, J. J. T., Jang, S., Jin, Y., Jung, G. Y., Chia, N., & Kim, P. (2017) · Nature Communications · doi:10.1038/ncomms15393 · Cited by 253
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Mao, Q., Jiang, F., Yin, R. H., Wang, J., Xia, W., Dong, G., Ma, W., Yang, Y., Xu, L., & Hu, J. (2017) · Cancer Letters · doi:10.1016/j.canlet.2017.11.036 · Cited by 253
Richards, J. L., Yap, Y. A., McLeod, K. H., Mackay, C. R., & Mariño, E. (2016) · Clinical & Translational Immunology · doi:10.1038/cti.2016.29 · Cited by 250
Wallen, Z. D., Appah, M., Dean, M. N., Sesler, C. L., Factor, S. A., Molho, E., Zabetian, C. P., Standaert, D. G., & Payami, H. (2020) · npj Parkinson s Disease · doi:10.1038/s41531-020-0112-6 · Cited by 252
Zhang, Z., Tang, H., Chen, P., Xie, H., & Tao, Y. (2019) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-019-0074-5 · Cited by 263
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Hand, T. W., Vujkovic-Cvijin, I., Ridaura, V. K., & Belkaid, Y. (2016) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2016.08.003 · Cited by 247
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Sujino, T., London, M., Hoytema van Konijnenburg, D. P., Rendon, T., Buch, T., Silva, H. M., Lafaille, J. J., Reis, B. S., & Mucida, D. (2016) · Science · doi:10.1126/science.aaf3892 · Cited by 250
Mishima, E., Fukuda, S., Mukawa, C., Yuri, A., Kanemitsu, Y., Matsumoto, Y., Akiyama, Y., Fukuda, N. N., Tsukamoto, H., Asaji, K., et al. (2017) · Kidney International · doi:10.1016/j.kint.2017.02.011 · Cited by 253
Self-citationSignaling networks in immunometabolism
Saravia, J., Raynor, J. L., Chapman, N. M., Lim, S. A., & Chi, H. (2020) · Cell Research · doi:10.1038/s41422-020-0301-1 · Cited by 258
A comprehensive framework for early-onset colorectal cancer research
Eng, C., Jacome, A. A. D. A., Agarwal, R., Hayat, M. H., Byndloss, M. X., Holowatyj, A. N., Bailey, C., & Lieu, C. H. (2022) · The Lancet Oncology · doi:10.1016/s1470-2045(21)00588-x · Cited by 264
Metadata
- Authors
- Furusawa, Y., Obata, Y., Fukuda, S., Endo, T. A., Nakato, G., Takahashi, D., Nakanishi, Y., Uetake, C., Kato, K., Kato, T., Takahashi, M., Fukuda, N. N., Murakami, S., Miyauchi, E., Hino, S., Atarashi, K., Onawa, S., Fujimura, Y., Lockett, T., Clarke, J. M., Topping, D. L., Tomita, M., Hori, S., Ohara, O., Morita, T., Koseki, H., Kikuchi, J., Honda, K., Hase, K., & Ohno, H.
- Affiliations
- RIKEN Center for Integrative Medical Sciences (JP)
- Chiba University (JP)
- Institute for Advanced Biosciences, Keio University (JP)
- Shizuoka University (JP)
- Japan Science and Technology Agency (JP)
- Institute of Medical Science, The University of Tokyo (JP)
- Commonwealth Scientific and Industrial Research Organisation (AU)
- RIKEN Center for Sustainable Resource Science (JP)
- Corresponding author
- Fukuda, Shinji
- Hase, Koji
- Ohno, Hiroshi
- ORCID
- Obata, Yuuki
- Fukuda, Shinji
- Endo, Takaho A.
- Takahashi, Daisuke
- Kato, Keiko
- Kato, Tamotsu
- Takahashi, Masumi
- Murakami, Shinnosuke
- Miyauchi, Eiji
- Hino, Shingo
- Atarashi, Koji
- Fujimura, Yumiko
- Lockett, Trevor
- Clarke, Julie M.
- Tomita, Masaru
- Hori, Shohei
- Ohara, Osamu
- Morita, Tatsuya
- Koseki, Haruhiko
- Kikuchi, Jun
- Honda, Kenya
- Hase, Koji
- Ohno, Hiroshi
- Venue
- Nature
- Published
- 2013-11-13
- Volume
- 504
- Issue
- 7480
- Pages
- 446-450
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1999906527
- Cited by
- 5,549
- References
- 50
- Citations by year
- 2026: 611 · 2025: 525 · 2024: 506 · 2023: 471 · 2022: 526 · 2021: 583 · 2020: 494 · 2019: 398 · 2018: 399 · 2017: 328 · 2016: 309 · 2015: 220 · 2014: 160 · 2013: 2
- FWCI
- 103.09
- Type
- journal article
- Language
- en
- Update notices
- erratum (2014-02-12)
- Open access
- closed
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Japan Society for the Promotion of Science (23390123, 25660101, 25293114, 24249029, 24380072, 13J05482, 24117723, 23780131, 25513012, 13J02667)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Gastroenterology › Inflammatory Bowel Disease
- Keywords
- butyrate, regulatory T cells, colitis, short-chain fatty acids, Foxp3, histone H3 acetylation, gut microbiota, commensal microorganisms, microbial metabolites, colonic mucosa, Treg differentiation, host-microbe interactions, immune homeostasis, Clostridia
- MeSH terms
- Acetylation, Animals, Butyrates, Cell Differentiation, Colitis, Colon, Female, Fermentation, Germ-Free Life, Histones, Homeostasis, Intestinal Mucosa, Male, Magnetic Resonance Spectroscopy, Promoter Regions, Genetic, Symbiosis, Conserved Sequence, Lymphocyte Count, Adoptive Transfer, T-Lymphocytes, Regulatory, Mice, Forkhead Transcription Factors, Metabolome
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