The DOI matches its Crossref record; 25 of the 25 references it cites were found in a registry or an index.
Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation
Open accessAbstract
Intestinal microbes provide multicellular hosts with nutrients and confer resistance to infection. The delicate balance between pro- and anti-inflammatory mechanisms, essential for gut immune homeostasis, is affected by the composition of the commensal microbial community. Regulatory T cells (Treg cells) expressing transcription factor Foxp3 have a key role in limiting inflammatory responses in the intestine. Although specific members of the commensal microbial community have been found to potentiate the generation of anti-inflammatory Treg or pro-inflammatory T helper 17 (TH17) cells, the molecular cues driving this process remain elusive. Considering the vital metabolic function afforded by commensal microorganisms, we reasoned that their metabolic by-products are sensed by cells of the immune system and affect the balance between pro- and anti-inflammatory cells. We tested this hypothesis by exploring the effect of microbial metabolites on the generation of anti-inflammatory Treg cells. We found that in mice a short-chain fatty acid (SCFA), butyrate, produced by commensal microorganisms during starch fermentation, facilitated extrathymic generation of Treg cells. A boost in Treg-cell numbers after provision of butyrate was due to potentiation of extrathymic differentiation of Treg cells, as the observed phenomenon was dependent on intronic enhancer CNS1 (conserved non-coding sequence 1), essential for extrathymic but dispensable for thymic Treg-cell differentiation. In addition to butyrate, de novo Treg-cell generation in the periphery was potentiated by propionate, another SCFA of microbial origin capable of histone deacetylase (HDAC) inhibition, but not acetate, which lacks this HDAC-inhibitory activity. Our results suggest that bacterial metabolites mediate communication between the commensal microbiota and the immune system, affecting the balance between pro- and anti-inflammatory mechanisms.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“butyrate is capable of inducing Treg differentiation and controlling inflammation (17, 23, 24, 87).”
From The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication (2020) · cites this paper as [23]
Experimental — accuracy not yet measuredIn 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 [707]
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 [10]
In the citing paper
“SCFAs have context-dependent functions: they can promote the expansion of Treg cells and also improve effector T cell functions133–136.”
From Gut OncoMicrobiome Signatures (GOMS) as next-generation biomarkers for cancer immunotherapy (2023) · cites this paper as [133]
In the citing paper
“Pending further confirmation, these results suggest that SCFAs display context-dependent immune effects that range from the differentiation of Treg cells to the enhancement of effector T cell functions.”
From Melanoma and microbiota: Current understanding and future directions (2024) · cites this paper as [58]
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 [76]
In the citing paper
“emphasizing the importance of administration route and SCFA concentration for in vivo experiments (Arpaia et al., 2013).”
From Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System (2017) · cites this paper as Arpaia et al., 2013
In the citing paper
“Each of these functions operates independently, as numbers of cTregs in germ-free mice, which are starkly reduced in the absence of treatment, can be rescued by separate provision of acetate, propionate or butyrate (Arpaia et al., 2013; Smith et al., 2013).”
From Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System (2017) · cites this paper as Arpaia et al., 2013
In the citing paper
“Direct application of 50 mM butyrate by enema, however, did elicit an increase in cTregs”
From Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System (2017) · cites this paper as Arpaia et al., 2013
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 Arpaia 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 Arpaia et al., 2013
In the citing paper
“Arpaia et al. detected no significant changes at a concentration of 36 mM”
From Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System (2017) · cites this paper as Arpaia et al., 2013
In the citing paper
“likely because this lower quantity of butyrate was largely absorbed by the upper gastrointestinal tract before reaching the colon (Arpaia et al., 2013; Smith et al., 2013).”
From Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System (2017) · cites this paper as Arpaia 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 Arpaia et al., 2013
In the citing paper
“A subset of colonic regulatory CD4+ T cells lack differentiation in GF mice resulting from the absence of bacterial consortia capable of fermenting dietary fiber into short-chain fatty acids (SCFAs).105–107”
From Interaction between microbiota and immunity in health and disease (2020) · cites this paper as [105]
In the citing paper
“In mice, intake of dietary carbohydrates,105 certain probiotics,140 artificial sweeteners141 and emulsifiers142 can modulate host immunity and inflammation, in part mediated by compositional changes of the gut microbiome.”
From Interaction between microbiota and immunity in health and disease (2020) · cites this paper as [105]
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 [38]
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 [38]
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 [38]
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 [38]
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 [38]
In the citing paper
“In addition to butyrate, new-onset Treg generation in the periphery was enhanced by propionate (115).”
From Gut Microbiome as a Potential Factor for Modulating Resistance to Cancer Immunotherapy (2020) · cites this paper as [115]
In the citing paper
“Additionally, the mucosal immune system profoundly impacts gut barrier functions both in health and disease conditions, reviewed previously.48,179, 180, 181, 182, 183”
From Regulation of Intestinal Barrier Function by Microbial Metabolites (2021) · cites this paper as [179]
In the citing paper
“SCFAs promote the development of naive CD4+ T cells into regulatory T cells (31, 32), induce “tolerogenic” dendritic cells in the intestinal mucosa (33), and limit autoimmity (34, 35).”
From Respiratory viral infection-induced microbiome alterations and secondary bacterial pneumonia. (2018) · cites this paper as [32]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
The Microbial Metabolites, Short-Chain Fatty Acids, Regulate Colonic T reg Cell Homeostasis
Smith, P. M., Howitt, M. R., Panikov, N., Michaud, M., Gallini, C. A., Bohlooly-Y, M., Glickman, J. N., & Garrett, W. S. (2013) · Science · doi:10.1126/science.1241165 · Cited by 5,413
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
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
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
Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota
Atarashi, K., Tanoue, T., Oshima, K., Suda, W., Nagano, Y., Nishikawa, H., Fukuda, S., Saito, T., Narushima, S., Hase, K., et al. (2013) · Nature · doi:10.1038/nature12331 · Cited by 2,872
Regulatory T Cell Lineage Specification by the Forkhead Transcription Factor Foxp3
Fontenot, J. D., Rasmussen, J. P., Williams, L. M., Dooley, J., Farr, A. G., & Rudensky, A. Y. (2005) · Immunity · doi:10.1016/j.immuni.2005.01.016 · Cited by 2,302
Self-citationRound, J. L., & Mazmanian, S. K. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0909122107 · Cited by 2,233
Regulatory T cells prevent catastrophic autoimmunity throughout the lifespan of mice
Kim, J. M., Rasmussen, J. P., & Rudensky, A. Y. (2006) · Nature Immunology · doi:10.1038/ni1428 · Cited by 1,827
Self-citationRole of conserved non-coding DNA elements in the Foxp3 gene in regulatory T-cell fate
Zheng, Y., Josefowicz, S. Z., Chaudhry, A., Peng, X. P., Forbush, K. A., & Rudensky, A. Y. (2010) · Nature · doi:10.1038/nature08750 · Cited by 1,170
Self-citationPeripheral education of the immune system by colonic commensal microbiota
Lathrop, S. K., Bloom, S. M., Rao, S. M., Nutsch, K., Lio, C.-W., Santacruz, N., Peterson, D. A., Stappenbeck, T. S., & Hsieh, C.-S. (2011) · Nature · doi:10.1038/nature10434 · Cited by 1,034
Cited by
Sorted by citations
Items 801–900 of 1,027
Intestinal microbiota and its effects on the immune system
Rescigno, M. (2014) · Cellular Microbiology · doi:10.1111/cmi.12301 · Cited by 124
Autoimmune host–microbiota interactions at barrier sites and beyond
Ruff, W. E., & Kriegel, M. A. (2015) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2015.02.006 · Cited by 122
Standardised animal models of host microbial mutualism
Macpherson, A. J., & McCoy, K. D. (2014) · Mucosal Immunology · doi:10.1038/mi.2014.113 · Cited by 122
Organ-Specific and Memory Treg Cells: Specificity, Development, Function, and Maintenance
Gratz, I. K., & Campbell, D. (2014) · Frontiers in Immunology · doi:10.3389/fimmu.2014.00333 · Cited by 123
Nakajima, A., Kaga, N., Nakanishi, Y., Ohno, H., Miyamoto, J., Kimura, I., Hori, S., Sasaki, T., Hiramatsu, K., Okumura, K., et al. (2017) · The Journal of Immunology · doi:10.4049/jimmunol.1700248 · Cited by 120
Juanola, O., Ferrusquía‐Acosta, J., García-Villalba, R., Zapater, P., Magaz, M., Marín, A., Olivas, P., Baiges, A., Bellot, P., Turón, F., et al. (2019) · The FASEB Journal · doi:10.1096/fj.201901327r · Cited by 125
Dysbiosis: from fiction to function
Tiffany, C. R., & Bäumler, A. J. (2019) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00230.2019 · Cited by 127
Zhou, Y., Wang, Y., Quan, M., Zhao, H., & Jia, J. (2021) · Journal of Alzheimer s Disease · doi:10.3233/jad-201497 · Cited by 125
The maternal gut microbiome during pregnancy and offspring allergy and asthma
Gao, Y., Nanan, R. K. H., Macia, L., Tan, J., Sominsky, L., Quinn, T. P., O’Hely, M., Ponsonby, A., Tang, M. L. K., Collier, F., et al. (2021) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2021.07.011 · Cited by 129
The female reproductive tract microbiotas, inflammation, and gynecological conditions
Gholiof, M., Luca, E. A.-D., & Wessels, J. M. (2022) · Frontiers in Reproductive Health · doi:10.3389/frph.2022.963752 · Cited by 137
Cao, Q., Shen, M., Li, R., Liu, Y., Zeng, Z., Zhou, J., Niu, D., Zhang, Q., Wang, R., Yao, J., et al. (2025) · Journal of Neuroinflammation · doi:10.1186/s12974-025-03454-y · Cited by 138
Kim, B., Wang, Y.-C., Hespen, C. W., Espinosa, J., Salje, J., Rangan, K. J., Oren, D. A., Kang, J. Y., Pedicord, V. A., & Hang, H. C. (2019) · eLife · doi:10.7554/elife.45343 · Cited by 120
Epigenetic modifications of the immune system in health and disease
Obata, Y., Furusawa, Y., & Hase, K. (2015) · Immunology and Cell Biology · doi:10.1038/icb.2014.114 · Cited by 125
Antigen-specific regulatory T-cell responses to intestinal microbiota
Russler-Germain, E. V., Rengarajan, S., & Hsieh, C.-S. (2017) · Mucosal Immunology · doi:10.1038/mi.2017.65 · Cited by 123
Epigenetic regulation in bacterial infections: targeting histone deacetylases
Grabiec, A. M., & Potempa, J. (2017) · Critical Reviews in Microbiology · doi:10.1080/1040841x.2017.1373063 · Cited by 119
Origin and functions of pro-inflammatory cytokine producing Foxp3+ regulatory T cells
Pandiyan, P., & Zhu, J. (2015) · Cytokine · doi:10.1016/j.cyto.2015.07.005 · Cited by 124
The composition of the microbiota modulates allograft rejection
Lei, Y. M., Chen, L., Wang, Y., Stefka, A. T., Molinero, L. L., Theriault, B. R., Aquino-Michaels, K., Sivan, A., Nagler‐Anderson, C., Gajewski, T. F., et al. (2016) · Journal of Clinical Investigation · doi:10.1172/jci85295 · Cited by 119
Alameddine, J., Godefroy, E., Papargyris, L., Sarrabayrouse, G., Tabiasco, J., Bridonneau, C., Yazdanbakhsh, K., Sokol, H., Altare, F., & Jotereau, F. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00143 · Cited by 121
Role and Effective Therapeutic Target of Gut Microbiota in Heart Failure
Jia, Q., Li, H., Zhou, H., Zhang, X., Zhang, A., Xie, Y., Li, Y., Lv, S., & Zhang, J. (2019) · Cardiovascular Therapeutics · doi:10.1155/2019/5164298 · Cited by 119
Bai, Y., Li, Y., Marion, T. N., Tong, Y., Zaiss, M. M., Tang, Z., Zhang, Q., Liu, Y., & Luo, Y. (2020) · Journal of Autoimmunity · doi:10.1016/j.jaut.2020.102564 · Cited by 121
Song, B., Li, P., Yan, S., Liu, Y., Gao, M., Lv, H., Lv, Z., & Guo, Y. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.781934 · Cited by 119
Campbell, C., Dikiy, S., Bhattarai, S. K., Chinen, T., Matheis, F., Calafiore, M., Hoyos, B. E., Hanash, A. M., Mucida, D., Bucci, V., et al. (2018) · Immunity · doi:10.1016/j.immuni.2018.04.013 · Cited by 121
Self-citationXylitol’s Health Benefits beyond Dental Health: A Comprehensive Review
Salli, K. M., Lehtinen, M. J., Tiihonen, K., & Ouwehand, A. C. (2019) · Nutrients · doi:10.3390/nu11081813 · Cited by 119
Turroni, S., Magnani, M., Pukar, K. C., Lesnik, P., Vidal, H., & Heer, M. A. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2020.553929 · Cited by 132
Gut Microbiota in Intestinal and Liver Disease
Jones, R. M., & Neish, A. S. (2020) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathol-030320-095722 · Cited by 117
Dysbiotic microbiota interactions in Crohn’s disease
Caparrós, E., Wiest, R., Scharl, M. M., Rogler, G., Gutiérrez, A., Yılmaz, B., Wawrzyniak, M., & Francés, R. (2021) · Gut Microbes · doi:10.1080/19490976.2021.1949096 · Cited by 123
Magliocca, G., Mone, P., Iorio, B. R. D., Heidland, A., & Marzocco, S. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23105354 · Cited by 130
Short chain fatty acids, a possible treatment option for autoimmune diseases
Golpour, F., Abbasi-Alaei, M., Babaei, F., Mirzababaei, M., Parvardeh, S., Mohammadi, G., & Nassiri‐Asl, M. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.114763 · Cited by 123
Relationship between gut microbiota and development of T cell associated disease
Kosiewicz, M. M., Dryden, G. W., Chhabra, A., & Alard, P. (2014) · FEBS Letters · doi:10.1016/j.febslet.2014.03.019 · Cited by 120
Foley, K. A., MacFabe, D. F., Vaz, A., Ossenkopp, K., & Kavaliers, M. (2014) · International Journal of Developmental Neuroscience · doi:10.1016/j.ijdevneu.2014.04.001 · Cited by 116
Implications of Diet and The Gut Microbiome in Neuroinflammatory and Neurodegenerative Diseases
Hirschberg, S., Gisevius, B., Duscha, A., & Haghikia, A. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20123109 · Cited by 120
Gut Microbiome as a Potential Factor for Modulating Resistance to Cancer Immunotherapy
Shui, L., Yang, X., Li, J., Yi, C., Sun, Q., & Zhu, H. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2019.02989 · Cited by 115
Role of Metabolism in the Immunobiology of Regulatory T Cells
Galgani, M., Rosa, V. D., Cava, A. L., & Matarese, G. (2016) · The Journal of Immunology · doi:10.4049/jimmunol.1600242 · Cited by 115
The Influence of the Microbiome on Allergic Sensitization to Food
Plunkett, C. H., & Nagler‐Anderson, C. (2017) · The Journal of Immunology · doi:10.4049/jimmunol.1601266 · Cited by 118
Regulatory T Cell and Forkhead Box Protein 3 as Modulators of Immune Homeostasis
Pereira, L. M. S., Gomes, S. T. M., Ishak, R., & Vallinoto, A. C. R. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.00605 · Cited by 121
Jiminez, J. A., Uwiera, T. C., Abbott, D. W., Uwiera, R. R. E., & Inglis, G. D. (2017) · mSphere · doi:10.1128/msphere.00243-17 · Cited by 124
Mendieta, E. J. L., Clooney, A. G., Carretero-Gomez, J. F., Moran, C. P., Sheehan, D., Nolan, J. A., Hill, C., Gahan, C. G. M., Joyce, S. A., Shanahan, F., et al. (2017) · Journal of Crohn s and Colitis · doi:10.1093/ecco-jcc/jjx137 · Cited by 119
Gut Vibes in Parkinson's Disease: The Microbiota‐Gut‐Brain Axis
Bullich‐Vilarrubias, C., Keshavarzian, A., Garssen, J., Kraneveld, A. D., & Perez‐Pardo, P. (2019) · Movement Disorders Clinical Practice · doi:10.1002/mdc3.12840 · Cited by 120
Gut microbiota and bone metabolism
Lu, L., Chen, X., Liu, Y., & Yu, X. (2021) · The FASEB Journal · doi:10.1096/fj.202100451r · Cited by 127
Canine chronic enteropathy—Current state-of-the-art and emerging concepts
Jergens, A. E., & Heilmann, R. M. (2022) · Frontiers in Veterinary Science · doi:10.3389/fvets.2022.923013 · Cited by 116
Systematic low-grade chronic inflammation and intrinsic mechanisms in polycystic ovary syndrome
Deng, H., Chen, Y., Xing, J., Zhang, N., & Xu, L. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1470283 · Cited by 146
Commensal microbiota regulates T cell fate decision in the gut
Furusawa, Y., Obata, Y., & Hase, K. (2014) · Seminars in Immunopathology · doi:10.1007/s00281-014-0455-3 · Cited by 121
de Groot, P. F., Nikolić, T., Imangaliyev, S., Bekkering, S., Duinkerken, G., Keij, F. M., Herrema, H., Winkelmeijer, M., Kroon, J., Levin, E., et al. (2020) · Diabetologia · doi:10.1007/s00125-019-05073-8 · Cited by 117
Brink, L., Mercer, K. E., Piccolo, B. D., Chintapalli, S. V., Elolimy, A. A., Bowlin, A. K., Matazel, K. S., Pack, L., Adams, S. H., Shankar, K., et al. (2020) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/nqaa076 · Cited by 115
Sommer, K., Wiendl, M., Müller, T. M., Heidbreder, K., Voskens, C., Neurath, M. F., & Zundler, S. (2021) · Frontiers in Medicine · doi:10.3389/fmed.2021.643973 · Cited by 125
Kibbie, J. J., Dillon, S. M., Thompson, T. A., Purba, C. M., McCarter, M. D., & Wilson, C. C. (2021) · Immunobiology · doi:10.1016/j.imbio.2021.152126 · Cited by 126
Mucus-degrading Bacteroides link carbapenems to aggravated graft-versus-host disease
Hayase, E., Hayase, T., Jamal, M. A., Miyama, T., Chang, C., Ortega, M. R., Ahmed, S., Karmouch, J. L., Sanchez, C. A., Brown, A. N., et al. (2022) · Cell · doi:10.1016/j.cell.2022.09.007 · Cited by 116
Mohebali, N., Weigel, M., Hain, T., Sütel, M., Bull, J., Kreikemeyer, B., & Breitrück, A. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.115568 · Cited by 125
Verma, A., Bhagchandani, T., Rai, A., Nikita, N., Sardarni, U. K., Bhavesh, N. S., Gulati, S., Malik, R., & Tandon, R. (2024) · ACS Omega · doi:10.1021/acsomega.3c05846 · Cited by 127
Song, Y., Malmuthuge, N., Steele, M. A., & Guan, L. L. (2017) · FEMS Microbiology Ecology · doi:10.1093/femsec/fix179 · Cited by 115
Gut microbiota and allergy: the importance of the pregnancy period
Abrahamsson, T., Wu, R., & Jenmalm, M. C. (2014) · Pediatric Research · doi:10.1038/pr.2014.165 · Cited by 116
Ciarlo, E., Heinonen, T., Herderschee, J., Fenwick, C. W., Mombelli, M., Roy, D. L., & Roger, T. (2016) · Scientific Reports · doi:10.1038/srep37944 · Cited by 122
Bonomo, R. R., Cook, T. M., Gavini, C. K., White, C. R., Jones, J. R., Bovo, E., Zima, A. V., Brown, I. A., Dugas, L. R., Zakharian, E., et al. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2006065117 · Cited by 114
Gut microbiome and Parkinson's disease: Perspective on pathogenesis and treatment
Salim, S., Ahmad, F. A., Banu, A., & Mohammad, F. (2022) · Journal of Advanced Research · doi:10.1016/j.jare.2022.10.013 · Cited by 124
Deciphering the tête-à-tête between the microbiota and the immune system
Surana, N. K., & Kasper, D. L. (2014) · Journal of Clinical Investigation · doi:10.1172/jci72332 · Cited by 120
Microbial imbalance and intestinal pathologies: connections and contributions
Yang, Y., & Jobin, C. (2014) · Disease Models & Mechanisms · doi:10.1242/dmm.016428 · Cited by 118
Schmidt, A., Eriksson, M., Shang, M.-M., Weyd, H., & Tegner, J. N. (2016) · PLoS ONE · doi:10.1371/journal.pone.0148474 · Cited by 119
Felizardo, R. J. F., de Almeida, D. C., Pereira, R. L., Watanabe, I. K. M., Doimo, N. T. S., Ribeiro, W. R., Cenedeze, M. A., Hiyane, M. I., Amano, M. T., Braga, T. T., et al. (2019) · The FASEB Journal · doi:10.1096/fj.201901080r · Cited by 116
Maternal microbiota-derived metabolic profile in fetal murine intestine, brain and placenta
Pessa‐Morikawa, T., Husso, A., Kärkkäinen, O. K., Koistinen, V., Hanhineva, K., Iivanainen, A., & Niku, M. (2022) · BMC Microbiology · doi:10.1186/s12866-022-02457-6 · Cited by 118
The gut microbiome and cancer: from tumorigenesis to therapy
Nobels, A., van Marcke, C., Jordan, B. F., Hul, M. V., & Cani, P. D. (2025) · Nature Metabolism · doi:10.1038/s42255-025-01287-w · Cited by 126
Gut microbiota-mediated immunomodulation in tumor
Liu, X., Chen, Y., Zhang, S., & Dong, L. (2021) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-021-01983-x · Cited by 112
Vitamin D and Microbiota: Is There a Link with Allergies?
Murdaca, G., Gerosa, A., Paladin, F., Petrocchi, L., Banchero, S., & Gangemi, S. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22084288 · Cited by 121
Zhao, Z., Wang, Z., Zhou, D., Han, Y., Ma, F., Hu, Z., Xin, F., Liu, X., Ren, T., Zhang, F., et al. (2021) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2021.05.006 · Cited by 113
Liu, X., Zhou, M., Dai, Z., Luo, S., Shi, Y., He, Z., & Chen, Y. (2022) · Phytotherapy Research · doi:10.1002/ptr.7636 · Cited by 112
Maguire, M., & Maguire, G. (2018) · Reviews in the Neurosciences · doi:10.1515/revneuro-2018-0024 · Cited by 114
The gut microbiota and graft-versus-host disease
Fredricks, D. N. (2019) · Journal of Clinical Investigation · doi:10.1172/jci125797 · Cited by 115
Camilleri, M., Lyle, B. J., Madsen, K. L., Sonnenburg, J. L., Verbeke, K., & Wu, G. D. (2019) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00063.2019 · Cited by 115
Microbial metabolites control gut inflammatory responses
Arpaia, N., & Rudensky, A. Y. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1323183111 · Cited by 112
Self-citationHealthy hosts rule within: ecological forces shaping the gut microbiota
Byndloss, M. X., Pernitzsch, S. R., & Bäumler, A. J. (2018) · Mucosal Immunology · doi:10.1038/s41385-018-0010-y · Cited by 109
Miles, J. P., Zou, J., Kumar, M.-V., Pellizzon, M., Ulman, E. A., Ricci, M. R., Gewirtz, A. T., & Chassaing, B. (2017) · Inflammatory Bowel Diseases · doi:10.1097/mib.0000000000001155 · Cited by 111
Microbiota-accessible pectic poly- and oligosaccharides in gut health
Tingirikari, J. M. R. (2018) · Food & Function · doi:10.1039/c8fo01296b · Cited by 110
Early-life factors contributing to type 1 diabetes
Craig, M. E., Kim, K. W., Isaacs, S. R., Penno, M. A. S., Hamilton‐Williams, E. E., Couper, J., & Rawlinson, W. D. (2019) · Diabetologia · doi:10.1007/s00125-019-4942-x · Cited by 114
Immunomodulatory roles of microbiota-derived short-chain fatty acids in bacterial infections
Ranjbar, R., Vahdati, S. N., Tavakoli, S., Khodaie, R., & Behboudi, H. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2021.111817 · Cited by 113
Gut microbial metabolites SCFAs and chronic kidney disease
Meng, H., Wei, W., Zhang, Y., Xiang, Z., Peng, D., Kasimumali, A., & Rong, S. (2024) · Journal of Translational Medicine · doi:10.1186/s12967-024-04974-6 · Cited by 121
Immunity, microbiota and kidney disease
Knauf, F., Brewer, J. R., & Flavell, R. A. (2019) · Nature Reviews Nephrology · doi:10.1038/s41581-019-0118-7 · Cited by 112
Liu, B., Zhu, X., Cui, Y., Wang, W., Liu, H., Li, Z., Guo, Z., Ma, S., Li, D., Wang, C., et al. (2021) · mSystems · doi:10.1128/msystems.00591-20 · Cited by 115
Self-citationZhang, H., Jiang, F., Zhang, J., Wang, W., Li, L., & Yan, J. (2022) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2022.01.166 · Cited by 114
Sun, J., Chen, F., & Wu, G. (2023) · The ISME Journal · doi:10.1038/s41396-023-01483-0 · Cited by 118
Gut microbiome and bone: To build, destroy, or both?
Yan, J., & Charles, J. F. (2017) · Current Osteoporosis Reports · doi:10.1007/s11914-017-0382-z · Cited by 108
Microbiota–Host Transgenomic Metabolism, Bioactive Molecules from the Inside
Turroni, S., Brigidi, P., Cavalli, A., & Candela, M. (2017) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.7b00244 · Cited by 111
Short-Chain Fatty Acids Modulate Healthy Gut Microbiota Composition and Functional Potential
Peterson, C. T., Pérez‐Santiago, J., Iablokov, S. N., Chopra, D., Rodionov, D. A., & Peterson, S. N. (2022) · Current Microbiology · doi:10.1007/s00284-022-02825-5 · Cited by 108
The kinase DYRK1A reciprocally regulates the differentiation of Th17 and regulatory T cells
Khor, B., Gagnon, J. D., Goel, G., Roche, M. I., Conway, K. L., Tran, K. A., Aldrich, L. N., Sundberg, T. B., Paterson, A. M., Mordecai, S., et al. (2015) · eLife · doi:10.7554/elife.05920 · Cited by 108
Host parasite communications—Messages from helminths for the immune system
Coakley, G., Buck, A. H., & Maizels, R. M. (2016) · Molecular and Biochemical Parasitology · doi:10.1016/j.molbiopara.2016.06.003 · Cited by 112
Recipient mucosal-associated invariant T cells control GVHD within the colon
Varelias, A., Bunting, M. D., Ormerod, K. L., Koyama, M., Olver, S. D., Straube, J., Kuns, R. D., Robb, R. J., Henden, A. S., Cooper, L. T., et al. (2018) · Journal of Clinical Investigation · doi:10.1172/jci91646 · Cited by 115
Regulatory T Cell Development in the Thymus
Owen, D. L., Sjaastad, L. E., & Farrar, M. A. (2019) · The Journal of Immunology · doi:10.4049/jimmunol.1900662 · Cited by 111
Resistant starch: Implications of dietary inclusion on gut health and growth in pigs: a review
Tan, F., Beltranena, E., & Zijlstra, R. T. (2021) · Journal of Animal Science and Biotechnology/Journal of animal science and biotechnology · doi:10.1186/s40104-021-00644-5 · Cited by 113
Risk Factors of Severe COVID-19: A Review of Host, Viral and Environmental Factors
Zsichla, L., & Müller, V. (2023) · Viruses · doi:10.3390/v15010175 · Cited by 121
Gray, L. E. K., O’Hely, M., Ranganathan, S., Sly, P. D., & Vuillermin, P. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.00365 · Cited by 110
Bilotta, A. J., & Cong, Y. (2019) · Precision Clinical Medicine · doi:10.1093/pcmedi/pbz008 · Cited by 113
Short-Chain Fatty Acids Augment Differentiation and Function of Human Induced Regulatory T Cells
Hu, M., Alhamwe, B. A., Santner‐Nanan, B., Miethe, S., Harb, H., Renz, H. E., Potaczek, D. P., & Nanan, R. K. H. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23105740 · Cited by 106
Differences in the gut microbiome and reduced fecal butyrate in elders with low skeletal muscle mass
Han, D., Wu, W., Liu, P., Yang, Y.-T., Hsu, H., Kuo, C., Wu, M., & Wang, T. (2022) · Clinical Nutrition · doi:10.1016/j.clnu.2022.05.008 · Cited by 109
Regulation of dietary fiber on intestinal microorganisms and its effects on animal health
Xue-bing, H., Ma, Y., Ding, S., Fang, J., & Liu, G. (2023) · Animal nutrition · doi:10.1016/j.aninu.2023.06.004 · Cited by 112
CD5 Instructs Extrathymic Regulatory T Cell Development in Response to Self and Tolerizing Antigens
Henderson, J. G., Opejin, A., Jones, A., Gross, C. J., & Hawiger, D. (2015) · Immunity · doi:10.1016/j.immuni.2015.02.010 · Cited by 111
Immunosuppressive effect of the gut microbiome altered by high-dose tacrolimus in mice
Zhang, Z., Liu, L., Tang, H., Jiao, W., Zeng, S., Xu, Y., Zhang, Q., Sun, Z., Mukherjee, A., Zhang, X., et al. (2018) · American Journal of Transplantation · doi:10.1111/ajt.14661 · Cited by 105
Commensal-bacteria-derived butyrate promotes the T-cell-independent IgA response in the colon
Isobe, J., Maeda, S., Obata, Y., Iizuka, K., Nakamura, Y., Fujimura, Y., Kimizuka, T., Hattori, K., Kim, Y., Morita, T., et al. (2019) · International Immunology · doi:10.1093/intimm/dxz078 · Cited by 105
Dendritic Cell Subsets in Intestinal Immunity and Inflammation
Sun, T., Nguyen, A., & Gommerman, J. L. (2020) · The Journal of Immunology · doi:10.4049/jimmunol.1900710 · Cited by 110
Rapid transcriptional and metabolic adaptation of intestinal microbes to host immune activation
Becattini, S., Sorbara, M. T., Kim, S. G., Littmann, E. R., Dong, Q., Walsh, G., Wright, R. J., Amoretti, L. A., Fontana, E., Hohl, T. M., et al. (2021) · Cell Host & Microbe · doi:10.1016/j.chom.2021.01.003 · Cited by 106
Microbial short-chain fatty acids: a strategy to tune adoptive T cell therapy
Rangan, P., & Mondino, A. (2022) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2021-004147 · Cited by 111
Interactions between microbiota and cervical epithelial, immune, and mucus barrier
Dong, M., Dong, Y., Bai, J., Li, H., Ma, X., Li, B., Wang, C., Li, H., Qi, W., Wang, Y., et al. (2023) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2023.1124591 · Cited by 113
Programmed and environmental determinants driving neonatal mucosal immune development
Torow, N., Hand, T. W., & Hornef, M. W. (2023) · Immunity · doi:10.1016/j.immuni.2023.02.013 · Cited by 110
Metadata
- Authors
- Arpaia, N., Campbell, C., Fan, X., Dikiy, S., van der Veeken, J., deRoos, P., Liu, H., Cross, J. R., Pfeffer, K., Coffer, P. J., & Rudensky, A. Y.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- Heinrich Heine University Düsseldorf (DE)
- Corresponding author
- Rudensky, Alexander Y.
- ORCID
- Venue
- Nature
- Published
- 2013-11-13
- Volume
- 504
- Issue
- 7480
- Pages
- 451-455
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3869884
- OpenAlex
- W2003342633
- Cited by
- 4,838
- References
- 25
- Citations by year
- 2026: 462 · 2025: 488 · 2024: 468 · 2023: 498 · 2022: 468 · 2021: 519 · 2020: 400 · 2019: 365 · 2018: 303 · 2017: 264 · 2016: 249 · 2015: 185 · 2014: 161 · 2013: 3
- FWCI
- 89.22
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- U.S. Public Health Service (T32A1007621)
- National Cancer Institute (T32CA009149, P30CA008748)
- National Institute of General Medical Sciences (T32GM007739)
- National Institute of Allergy and Infectious Diseases (R37AI034206, T32AI007621)
- 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
- Life Sciences › Immunology and Microbiology › Immunology › IL-33, ST2, and ILC Pathways
- Keywords
- short-chain fatty acids, regulatory T cells, Foxp3, commensal bacteria, gut microbiota, colitis, histone H3 acetylation, colonic mucosa, intestinal immune homeostasis, Clostridia, Th17 cells, microbial metabolites
- MeSH terms
- Acetylation, Animals, Butyrates, Cell Differentiation, Dendritic Cells, Enhancer Elements, Genetic, Fermentation, Histone Deacetylases, Intestinal Mucosa, Intestines, Introns, Male, Mice, Inbred C57BL, Starch, Symbiosis, Cytokines, Lymphocyte Count, Inflammation Mediators, T-Lymphocytes, Regulatory, Mice, Forkhead Transcription Factors
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
