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
Self-citation
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Items 701–800 of 1,050
Demirci, M., Tokman, H. B., Uysal, H. K., Demiryas, S., Karakullukcu, A., Saribas, S., Cokugras, H., & Kocazeybek, B. S. (2019) · Allergologia et Immunopathologia · doi:10.1016/j.aller.2018.12.009 · Cited by 150
Helicobacter species are potent drivers of colonic T cell responses in homeostasis and inflammation
Chai, J. N., Peng, Y., Rengarajan, S., Solomon, B. D., Ai, T. L., Shen, Z., Perry, J. S. A., Knoop, K. A., Tanoue, T., Narushima, S., et al. (2017) · Science Immunology · doi:10.1126/sciimmunol.aal5068 · Cited by 152
Self-citationKunisada, Y., Eikawa, S., Tomonobu, N., Domae, S., Uehara, T., Hori, S., Furusawa, Y., Hase, K., Sasaki, A., & Udono, H. (2017) · EBioMedicine · doi:10.1016/j.ebiom.2017.10.009 · Cited by 152
Self-citationPerinatal Interactions between the Microbiome, Immunity, and Neurodevelopment
Pronovost, G. N., & Hsiao, E. Y. (2019) · Immunity · doi:10.1016/j.immuni.2018.11.016 · Cited by 150
Phytochemicals and inflammatory bowel disease: a review
Hossen, I., Wu, H., Ting, L., Mehmood, A., Jingyi, S., Xu, D., Yanping, C., Hongqing, W., Zhipeng, G., Zhang, K., et al. (2019) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2019.1570913 · Cited by 157
The gut microbiome and cardiovascular disease: current knowledge and clinical potential
Ahmad, A. F., Dwivedi, G., O’Gara, F., Caparros-Martin, J. A., & Ward, N. C. (2019) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00376.2019 · Cited by 165
Toward Understanding Microbiome-Neuronal Signaling
Jameson, K. G., Olson, C. A., Kazmi, S. A., & Hsiao, E. Y. (2020) · Molecular Cell · doi:10.1016/j.molcel.2020.03.006 · Cited by 155
Emerging concepts in intestinal immune control of obesity-related metabolic disease
Khan, S. M., Luck, H., Winer, S., & Winer, D. A. (2021) · Nature Communications · doi:10.1038/s41467-021-22727-7 · Cited by 161
Gut microbiota and host metabolism in liver cirrhosis
Usami, M. (2015) · World Journal of Gastroenterology · doi:10.3748/wjg.v21.i41.11597 · Cited by 152
Fung, T. C., Bessman, N. J., Hepworth, M. R., Kumar, N., Shibata, N., Kobuley, D. E., Wang, K., Ziegler, C. G. K., Goc, J., Shima, T., et al. (2016) · Immunity · doi:10.1016/j.immuni.2016.02.019 · Cited by 148
Environmental factors in autoimmune diseases and their role in multiple sclerosis
Haase, S., Grohme, D. A., Erzler, M., Binsfeld, M., Haghikia, A., Müller, D. N., Linker, R. A., & Kleinewietfeld, M. (2016) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-016-2311-1 · Cited by 156
Gavin, P. G., Mullaney, J. A., Loo, D., Cao, K. L., Gottlieb, P. A., Hill, M. M. C., Zipris, D., & Hamilton‐Williams, E. E. (2018) · Diabetes Care · doi:10.2337/dc18-0777 · Cited by 148
Ma, T., Villot, C., Renaud, D. L., Skidmore, A. L., Chevaux, E., Steele, M. A., & Guan, L. L. (2020) · The ISME Journal · doi:10.1038/s41396-020-0678-3 · Cited by 161
Akamatsu, M., Mikami, N., Ohkura, N., Kawakami, R., Kitagawa, Y., Sugimoto, A., Hirota, K., Nakamura, N., Ujihara, S., Kurosaki, T., et al. (2019) · Science Immunology · doi:10.1126/sciimmunol.aaw2707 · Cited by 148
Dark matter in host-microbiome metabolomics: Tackling the unknowns–A review
Peisl, B. Y. L., Schymanski, E., & Wilmes, P. (2017) · Analytica Chimica Acta · doi:10.1016/j.aca.2017.12.034 · Cited by 152
Raimondi, I., Izzo, L., Tunesi, M., Comar, M., Albani, D., & Giordano, C. (2020) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2019.00435 · Cited by 150
Vuillermin, P., O’Hely, M., Collier, F., Allen, K. J., Tang, M. L. K., Harrison, L. C., Carlin, J. B., Saffery, R., Ranganathan, S., Sly, P. D., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-14552-1 · Cited by 151
Self-citationThe correlation between the Th17/Treg cell balance and bone health
Zhu, L., Hua, F., Ding, W., Ding, K., Zhang, Y., & Xu, C. (2020) · Immunity & Ageing · doi:10.1186/s12979-020-00202-z · Cited by 146
Rapid and Efficient Generation of Regulatory T Cells to Commensal Antigens in the Periphery
Nutsch, K., Chai, J. N., Ai, T. L., Russler-Germain, E. V., Feehley, T., Nagler‐Anderson, C., & Hsieh, C. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.08.092 · Cited by 151
Histone deacetylase function in CD4+ T cells
Ellmeier, W., & Seiser, C. (2018) · Nature reviews. Immunology · doi:10.1038/s41577-018-0037-z · Cited by 146
Cross talk between neutrophils and the microbiota
Zhang, D., & Frenette, P. S. (2019) · Blood · doi:10.1182/blood-2018-11-844555 · Cited by 153
Ferrer-Picón, E., Dotti, I., Corraliza, A. M., Mayorgas, A., Esteller, M., Perales, J. C., Ricart, E., Masamunt, M. C., Carrasco, A., Tristán, E., et al. (2019) · Inflammatory Bowel Diseases · doi:10.1093/ibd/izz119 · Cited by 151
Cait, A., Cardenas, E., Dimitriu, P. A., Amenyogbe, N., Dai, D. L., Cait, J., Sbihi, H., Stiemsma, L. T., Subbarao, P., Mandhane, P. J., et al. (2019) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2019.06.029 · Cited by 149
Diet, gut microbiota and cognition
Proctor, C., Thiennimitr, P., Chattipakorn, N., & Chattipakorn, S. C. (2017) · Metabolic Brain Disease · doi:10.1007/s11011-016-9917-8 · Cited by 144
The mucosal immune system for vaccine development
Lamichhane, A., Azegami, T., & Kiyono, H. (2014) · Vaccine · doi:10.1016/j.vaccine.2014.08.089 · Cited by 153
Dietary Fiber Pectin Ameliorates Experimental Colitis in a Neutral Sugar Side Chain-Dependent Manner
Ishisono, K., Mano, T., Yabe, T., & Kitaguchi, K. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.02979 · Cited by 147
Immunological Mechanisms in Inflammation-Associated Colon Carcinogenesis
Hirano, T., Hirayama, D., Wagatsuma, K., Yamakawa, T., Yokoyama, Y., & Nakase, H. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21093062 · Cited by 147
Willers, M., Ulas, T., Völlger, L., Vogl, T., Heinemann, A. S., Pirr, S., Pagel, J., Fehlhaber, B., Halle, O., Schöning, J., et al. (2020) · Gastroenterology · doi:10.1053/j.gastro.2020.08.019 · Cited by 145
Gut dysbiosis: Ecological causes and causative effects on human disease
Winter, S., & Bäumler, A. J. (2023) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2316579120 · Cited by 160
Enteric nervous system: the bridge between the gut microbiota and neurological disorders
Geng, Z.-H., Zhu, Y., Li, Q.-L., Zhao, C., & Zhou, P.-H. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.810483 · Cited by 144
Hurst, N. R., Kendig, D. M., Murthy, K. S., & Grider, J. R. (2014) · Neurogastroenterology & Motility · doi:10.1111/nmo.12425 · Cited by 147
Induction of regulatory T cells: A role for probiotics and prebiotics to suppress autoimmunity
Dwivedi, M., Kumar, P., Laddha, N. C., & Kemp, E. H. (2016) · Autoimmunity Reviews · doi:10.1016/j.autrev.2016.01.002 · Cited by 145
Impact of prebiotics on immune response: from the bench to the clinic
Pujari, R., & Banerjee, G. (2020) · Immunology and Cell Biology · doi:10.1111/imcb.12409 · Cited by 154
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Yin, H., Liu, N., & Chen, J. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.845684 · Cited by 151
The intestinal microbiome in spondyloarthritis
Gill, T., Asquith, M. J., Rosenbaum, J. T., & Colbert, R. A. (2015) · Current Opinion in Rheumatology · doi:10.1097/bor.0000000000000187 · Cited by 152
Regulation of Innate and Adaptive Immunity by TGFβ
Kelly, A., Houston, S. A., Sherwood, E., Casulli, J., & Travis, M. A. (2017) · Advances in immunology · doi:10.1016/bs.ai.2017.01.001 · Cited by 145
Daïen, C., Pinget, G. V., Tan, J. K., & Macia, L. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.00548 · Cited by 147
Zhang, J., Zhang, F., Zhao, C., Xu, Q., Liang, C., Yang, Y., Wang, H., Shang, Y., Wang, Y., Mu, X., et al. (2018) · Endocrine · doi:10.1007/s12020-018-1831-x · Cited by 146
Suda, K., & Matsuda, K. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23031172 · Cited by 154
Butyrate as a promising therapeutic target in cancer: From pathogenesis to clinic (Review)
Sun, J., Chen, S., Zang, D., Sun, H., Sun, Y., & Chen, J. (2024) · International Journal of Oncology · doi:10.3892/ijo.2024.5632 · Cited by 157
Regulatory T cell identity: formation and maintenance
Li, X., & Zheng, Y. (2015) · Trends in Immunology · doi:10.1016/j.it.2015.04.006 · Cited by 150
Abdollahi‐Roodsaz, S., Abramson, S. B., & Scher, J. U. (2016) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2016.68 · Cited by 142
Yasueda, A., Mizushima, T., Nezu, R., Sumi, R., Tanaka, M., Nishimura, J., Kai, Y., Hirota, M., Osawa, H., Nakajima, K., et al. (2015) · Surgery Today · doi:10.1007/s00595-015-1261-9 · Cited by 141
A clinical update on the significance of the gut microbiota in systemic autoimmunity
Rosser, E. C., & Mauri, C. (2016) · Journal of Autoimmunity · doi:10.1016/j.jaut.2016.06.009 · Cited by 142
The microbiota-gut-bone axis and bone health
Tu, Y., Yang, R., Xu, X., & Zhou, X. (2021) · Journal of Leukocyte Biology · doi:10.1002/jlb.3mr0321-755r · Cited by 144
Role of the microbiota in response to and recovery from cancer therapy
Blake, S. J., Wolf, Y., Boursi, B., & Lynn, D. J. (2023) · Nature reviews. Immunology · doi:10.1038/s41577-023-00951-0 · Cited by 151
SLE: Another Autoimmune Disorder Influenced by Microbes and Diet?
Mu, Q., Zhang, H., & Luo, X. (2015) · Frontiers in Immunology · doi:10.3389/fimmu.2015.00608 · Cited by 147
Early life factors that affect allergy development
Reynolds, L. A., & Finlay, B. B. (2017) · Nature reviews. Immunology · doi:10.1038/nri.2017.39 · Cited by 140
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Canani, R. B., Paparo, L., Nocerino, R., Scala, C. D., Gatta, G. D., Maddalena, Y., Buono, A., Bruno, C., Voto, L., & Ercolini, D. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00191 · Cited by 145
Butyrate as a bioactive human milk protective component against food allergy
Paparo, L., Nocerino, R., Ciaglia, E., Scala, C. D., Caro, C. D., Russo, R., Trinchese, G., Aitoro, R., Amoroso, A., Bruno, C., et al. (2020) · Allergy · doi:10.1111/all.14625 · Cited by 141
Gut-Brain Connection: Microbiome, Gut Barrier, and Environmental Sensors
Gwak, M.-G., & Chang, S. (2021) · Immune Network · doi:10.4110/in.2021.21.e20 · Cited by 151
Prospects for clinical applications of butyrate-producing bacteria
Zhu, L., Zhang, Y., Huang, H.-H., & Lin, J. (2021) · World Journal of Clinical Pediatrics · doi:10.5409/wjcp.v10.i5.84 · Cited by 140
Deoxynivalenol, gut microbiota and immunotoxicity: A potential approach?
Liao, Y., Peng, Z., Chen, L., Nussler, A. K., Liu, L., & Yang, W. Q. (2018) · Food and Chemical Toxicology · doi:10.1016/j.fct.2018.01.013 · Cited by 138
Molecules Produced by Probiotics and Intestinal Microorganisms with Immunomodulatory Activity
Delgado, S., Sánchez, B., Margollés, A., Ruas‐Madiedo, P., & Ruíz, L. (2020) · Nutrients · doi:10.3390/nu12020391 · Cited by 139
Dietary fiber metabolites regulate innate lymphoid cell responses
Sepahi, A., Liu, Q., Friesen, L., & Kim, C. H. (2020) · Mucosal Immunology · doi:10.1038/s41385-020-0312-8 · Cited by 143
Wang, R., Cao, S., Bashir, M. E. H., Hesser, L. A., Su, Y., Hong, S. M. C., Thompson, A., Culleen, E., Sabados, M., Dylla, N. P., et al. (2022) · Nature Biomedical Engineering · doi:10.1038/s41551-022-00972-5 · Cited by 140
Microbial Metabolites Determine Host Health and the Status of Some Diseases
Sittipo, P., Shim, J., & Lee, Y. K. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20215296 · Cited by 146
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Wang, M.-X., Li, L., Chen, Y.-D., Zhong, Y., Lin, Y., Li, P., Tian, X., Han, B. R., Xie, Z., & Liao, Q. (2020) · Pharmacological Research · doi:10.1016/j.phrs.2020.104978 · Cited by 142
Role of gut microbiome in cancer immunotherapy: from predictive biomarker to therapeutic target
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Gut microbiota-derived metabolites tune host homeostasis fate
Kim, S., Seo, S., & Kweon, M. (2024) · Seminars in Immunopathology · doi:10.1007/s00281-024-01012-x · Cited by 156
Hoffmann, T. W., Pham, H., Bridonneau, C., Aubry, C., Lamas, B., Martin‐Gallausiaux, C., Moroldo, M., Rainteau, D. P., Lapaque, N., Six, A., et al. (2015) · The ISME Journal · doi:10.1038/ismej.2015.127 · Cited by 144
Mechanistic links between gut microbial community dynamics, microbial functions and metabolic health
Ha, C. W. (2014) · World Journal of Gastroenterology · doi:10.3748/wjg.v20.i44.16498 · Cited by 137
Stilling, R. M., Bordenstein, S. R., Dinan, T. G., & Cryan, J. F. (2014) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2014.00147 · Cited by 139
The Intersection of Immune Responses, Microbiota, and Pathogenesis in Giardiasis
Fink, M. Y., & Singer, S. M. (2017) · Trends in Parasitology · doi:10.1016/j.pt.2017.08.001 · Cited by 137
Core Gut Bacteria Analysis of Healthy Mice
Wang, J., Lang, T., Shen, J., Dai, J., Tian, L., & Wang, X. (2019) · Frontiers in Microbiology · doi:10.3389/fmicb.2019.00887 · Cited by 141
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Jian, X., Zhu, Y., Ouyang, J., Wang, Y., Lei, Q., Xia, J., Guan, Y., Zhang, J., Guo, J., He, Y., et al. (2020) · Microbiome · doi:10.1186/s40168-020-00854-5 · Cited by 144
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Kopczyńska, J., & Kowalczyk, M. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1380476 · Cited by 160
Manor, O., Levy, R., Pope, C. E., Hayden, H. S., Brittnacher, M., Carr, R., Radey, M. C., Hager, K. R., Heltshe, S. L., Ramsey, B. W., et al. (2016) · Scientific Reports · doi:10.1038/srep22493 · Cited by 133
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Basson, A. R., Trotter, A., Rodriguez‐Palacios, A., & Cominelli, F. (2016) · Frontiers in Immunology · doi:10.3389/fimmu.2016.00290 · Cited by 140
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Aitoro, R., Paparo, L., Amoroso, A., Costanzo, M. D., Cosenza, L., Granata, V., Scala, C. D., Nocerino, R., Trinchese, G., Montella, M. O., et al. (2017) · Nutrients · doi:10.3390/nu9070672 · Cited by 138
Transcriptional regulation and development of regulatory T cells
Lee, W., & Lee, G. R. (2018) · Experimental & Molecular Medicine · doi:10.1038/emm.2017.313 · Cited by 147
Role of probiotics and prebiotics in immunomodulation
Yahfoufi, N., Mallet, J., Graham, É. A., & Matar, C. (2018) · Current Opinion in Food Science · doi:10.1016/j.cofs.2018.04.006 · Cited by 143
Dsouza, M., Menon, R., Crossette, E. M., Bhattarai, S. K., Schneider, J., Kim, Y., Reddy, S., Caballero, S., Felix, C. R., Cornacchione, L. P., et al. (2022) · Cell Host & Microbe · doi:10.1016/j.chom.2022.03.016 · Cited by 142
Microbiota-derived acetate enhances host antiviral response via NLRP3
Niu, J., Cui, M., Yang, X., Li, J., Yao, Y., Guo, Q., Lu, A., Qi, X., Zhou, D., Zhang, C., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-36323-4 · Cited by 140
The microbiome and its potential as a cancer preventive intervention
Bultman, S. J. (2016) · Seminars in Oncology · doi:10.1053/j.seminoncol.2015.09.001 · Cited by 134
Gut Microbiome and Osteoporosis
Ding, K., Hua, F., & Ding, W. (2020) · Aging and disease · doi:10.14336/ad.2019.0523 · Cited by 134
Fecal microbiota transplantation reverses antibiotic and chemotherapy-induced gut dysbiosis in mice
Le Bastard, Q., Ward, T., Sidiropoulos, D., Hillmann, B. M., Chun, C. L., Sadowsky, M. J., Knights, D., & Montassier, E. (2018) · Scientific Reports · doi:10.1038/s41598-018-24342-x · Cited by 134
Breast-fed and bottle-fed infant rhesus macaques develop distinct gut microbiotas and immune systems
Ardeshir, A., Narayan, N. R., Méndez-Lagares, G., Lu, D., Rauch, M., Huang, Y., Van Rompay, K. K. A., Lynch, S. V., & Hartigan-O’Connor, D. J. (2014) · Science Translational Medicine · doi:10.1126/scitranslmed.3008791 · Cited by 134
Maranduba, C. M. D. C., de Castro, S. B. R., de Souza, G. T., Rossato, C., da Guia, F. C., Valente, M. A. S., Rettore, J. V. P., Maranduba, C. P., de Souza, C. M., do Carmo, A. M. R., et al. (2015) · Journal of Immunology Research · doi:10.1155/2015/931574 · Cited by 137
Sivaprakasam, S., Gurav, A., Paschall, A. V., Coe, G. L., Chaudhary, K., Cai, Y., Kolhe, R. B., Martin, P. M., Browning, D. D., Huang, L., et al. (2016) · Oncogenesis · doi:10.1038/oncsis.2016.38 · Cited by 135
Diet, the intestinal microbiota, and immune health in aging
Clements, S. J., & Carding, S. R. (2016) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2016.1211086 · Cited by 163
Interplay between bile acids and the gut microbiota promotes intestinal carcinogenesis
Wang, S., Dong, W., Liu, L., Xu, M., Wang, Y., Liu, T., Zhang, Y., Wang, B., & Cao, H. (2019) · Molecular Carcinogenesis · doi:10.1002/mc.22999 · Cited by 135
Bell, K. J., Saad, S., Tillett, B. J., McGuire, H. M., Bordbar, S., Yap, Y. A., Nguyen, L. T., Wilkins, M. R., Corley, S., Brodie, S., et al. (2022) · Microbiome · doi:10.1186/s40168-021-01193-9 · Cited by 138
Fusobacterium and Enterobacteriaceae: Important players for CRC?
Allen‐Vercoe, E., & Jobin, C. (2014) · Immunology Letters · doi:10.1016/j.imlet.2014.05.014 · Cited by 137
The microbiota and autoimmunity: Their role in thyroid autoimmune diseases
Köhling, H.-L., Plummer, S. F., Marchesi, J. R., Davidge, K. S., & Ludgate, M. (2017) · Clinical Immunology · doi:10.1016/j.clim.2017.07.001 · Cited by 139
Role of Short Chain Fatty Acids in Controlling Tregs and Immunopathology During Mucosal Infection
Bhaskaran, N., Quigley, C., Paw, C., Butala, S., Schneider, E., & Pandiyan, P. (2018) · Frontiers in Microbiology · doi:10.3389/fmicb.2018.01995 · Cited by 136
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Alessandro de, S. I. R. E., de Sire, R., Curci, C., Castiglione, F., & Wahli, W. (2022) · Cells · doi:10.3390/cells11040743 · Cited by 144
Xu, L., Zhang, Y., Li, X., Li, C., Hu, H., Hu, J., Liu, M., Yang, Q. Z., Gu, P., Li, J., et al. (2025) · iMeta · doi:10.1002/imt2.270 · Cited by 143
Oral imazalil exposure induces gut microbiota dysbiosis and colonic inflammation in mice
Jin, C., Zeng, Z., Fu, Z., & Jin, Y. (2016) · Chemosphere · doi:10.1016/j.chemosphere.2016.06.105 · Cited by 132
Symbiont-induced odorant binding proteins mediate insect host hematopoiesis
Benoit, J. B., Vigneron, A., Broderick, N. A., Wu, Y., Sun, J. S., Carlson, J. R., Aksoy, S., & Weiss, B. L. (2017) · eLife · doi:10.7554/elife.19535 · Cited by 137
D’Souza, W. N., Douangpanya, J., Mu, S., Jaeckel, P., Zhang, M., Maxwell, J. R., Rottman, J. B., Labitzke, K., Willee, A., Beckmann, H., et al. (2017) · PLoS ONE · doi:10.1371/journal.pone.0180190 · Cited by 136
Li, M., Yue, H., Wang, Y., Guo, C., Du, Z., Jin, C., & Ding, K. (2020) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2020.01.305 · Cited by 133
Arresting microbiome development limits immune system maturation and resistance to infection in mice
Lubin, J., Green, J., Maddux, S., Denu, L., Duranova, T., Lanza, M. R., Wynosky-Dolfi, M. A., Flores, J. N., Grimes, L. P., Brodsky, I. E., et al. (2023) · Cell Host & Microbe · doi:10.1016/j.chom.2023.03.006 · Cited by 139
Fatty Acids, Lipid Mediators, and T-Cell Function
de Jong, A. J., Kloppenburg, M., Toes, R. E. M., & Ioan‐Facsinay, A. (2014) · Frontiers in Immunology · doi:10.3389/fimmu.2014.00483 · Cited by 134
White, C. A., Pone, E. J., Lam, T., Tat, C., Hayama, K. L., Li, G., Zan, H., & Casali, P. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1401702 · Cited by 131
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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