The DOI matches its Crossref record; 48 of the 48 references it cites were found in a registry or an index.
Activation of Gpr109a, Receptor for Niacin and the Commensal Metabolite Butyrate, Suppresses Colonic Inflammation and Carcinogenesis
Open accessAbstract
Commensal gut microflora and dietary fiber protect against colonic inflammation and colon cancer through unknown targets. Butyrate, a bacterial product from fermentation of dietary fiber in the colon, has been implicated in this process. GPR109A (encoded by Niacr1) is a receptor for butyrate in the colon. GPR109A is also a receptor for niacin, which is also produced by gut microbiota and suppresses intestinal inflammation. Here we showed that Gpr109a signaling promoted anti-inflammatory properties in colonic macrophages and dendritic cells and enabled them to induce differentiation of Treg cells and IL-10-producing T cells. Moreover, Gpr109a was essential for butyrate-mediated induction of IL-18 in colonic epithelium. Consequently, Niacr1(-/-) mice were susceptible to development of colonic inflammation and colon cancer. Niacin, a pharmacological Gpr109a agonist, suppressed colitis and colon cancer in a Gpr109a-dependent manner. Thus, Gpr10a has an essential role in mediating the beneficial effects of gut microbiota and dietary fiber in colon.
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“Singh et al. demonstrated that butyrate was an agonist for GPR109A [73].”
From Gut microbiota-mediated immunomodulation in tumor (2021) · cites this paper as [73]
In the citing paper
“Separately, butyrate has also been shown to enhance Treg generation by promoting an anti-inflammatory phenotype in macrophages and DCs through activation of HCAR2 (Singh et al., 2014).”
From Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System (2017) · cites this paper as Singh et al., 2014
In the citing paper
“However, SCFAs have also been shown to affect DC maturation and function through HCAR2 and FFAR3, depending on the context (Singh et al., 2014; Trompette et al., 2014).”
From Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System (2017) · cites this paper as Singh et al., 2014
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 Singh et al., 2014
In the citing paper
“In the gut, they influence expression of anti-inflammatory markers, such as interleukin (IL-)10 in macrophages and intestinal dendritic cells [55].”
From Effect of fecal microbiota transplant on symptoms of psychiatric disorders: a systematic review (2020) · cites this paper as [55]
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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
Host-Bacterial Mutualism in the Human Intestine
Bäckhed, F., Ley, R. E., Sonnenburg, J. L., Peterson, D. A., & Gordon, J. I. (2005) · Science · doi:10.1126/science.1104816 · Cited by 5,277
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
Recognition 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
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
Review article: the role of butyrate on colonic function
HAMER, H. M., JONKERS, D., VENEMA, K., VANHOUTVIN, S., TROOST, F. J., & BRUMMER, R. ‐. (2008) · Alimentary Pharmacology & Therapeutics · doi:10.1111/j.1365-2036.2007.03562.x · Cited by 2,721
Coombes, J. L., Siddiqui, K. R. R., Arancibia-Cárcamo, C. V., Hall, J. A., Sun, C., Belkaid, Y., & Powrie, F. M. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20070590 · Cited by 2,708
A microbial symbiosis factor prevents intestinal inflammatory disease
Mazmanian, S. K., Round, J. L., & Kasper, D. L. (2008) · Nature · doi:10.1038/nature07008 · Cited by 2,340
Round, J. L., & Mazmanian, S. K. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0909122107 · Cited by 2,233
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Items 101–135 of 135
Park, J., Goergen, C. J., HogenEsch, H., & Kim, C. H. (2016) · The Journal of Immunology · doi:10.4049/jimmunol.1502046 · Cited by 166
Sanford, J. A., Zhang, L.-J., Williams, M. R., Gangoiti, J. A., Huang, C.-M., & Gallo, R. L. (2016) · Science Immunology · doi:10.1126/sciimmunol.aah4609 · Cited by 166
Gut microbiota–derived short-chain fatty acids and kidney diseases
Li, L., Ma, L., & Fu, P. (2017) · Drug Design, Development and Therapy · doi:10.2147/dddt.s150825 · Cited by 164
Pan, X., Fang, X., Wang, F., Li, H., Niu, W., Liang, W., Wu, C., Li, J., Tu, X., Pan, L., et al. (2019) · British Journal of Pharmacology · doi:10.1111/bph.14806 · Cited by 151
The 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
Gut Microbiome and Osteoporosis
Ding, K., Hua, F., & Ding, W. (2020) · Aging and disease · doi:10.14336/ad.2019.0523 · Cited by 134
Guertin, K. A., Loftfield, E., Boca, S. M., Sampson, J. N., Moore, S. C., Xiao, Q., Huang, W.-Y., Xiong, X., Freedman, N. D., Cross, A. J., et al. (2015) · The American Journal of Clinical Nutrition · doi:10.3945/ajcn.114.096099 · Cited by 134
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
Food Fight: Role of Itaconate and Other Metabolites in Antimicrobial Defense
Luan, H. H., & Medzhitov, R. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.08.013 · Cited by 130
Regulatory T cells in the face of the intestinal microbiota
Ramanan, D., Pratama, A., Zhu, Y., Venezia, O., Sassone-Corsi, M., Chowdhary, K., Galván-Peña, S., Sefik, E., Brown, C., Gélineau, A., et al. (2023) · Nature Reviews Immunology · doi:10.1038/s41577-023-00890-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
Healthy 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
Beneficial effects of butyrate on brain functions: A view of epigenetic
Alpino, G. D. C. Á., Pereira-Sol, G. A., Dias, M. D. M. E., Aguiar, A. S. D., & Peluzio, M. D. C. G. (2024) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2022.2137776 · Cited by 110
Donovan, M., Mackey, C. S., Platt, G. N., Rounds, J., Brown, A. N., Trickey, D. J., Liu, Y., Jones, K. M., & Wang, Z. (2020) · Neurobiology of Stress · doi:10.1016/j.ynstr.2020.100278 · Cited by 85
Regulation of humoral immunity by gut microbial products
Kim, M., & Kim, C. H. (2017) · Gut Microbes · doi:10.1080/19490976.2017.1299311 · Cited by 104
Bishehsari, F., Engen, P. A., Voigt, R. M., Swanson, G., Shaikh, M., Wilber, S., Naqib, A., Green, S. J., Shetuni, B., Forsyth, C. B., et al. (2020) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2019.10.011 · Cited by 76
“Butyrate-GPR109A signaling can induce differentiation of intestinal FOXP3þ Tregs through innate immune cells, such as macrophages and dendritic cells.(46) Treg numbers also can be boosted by butyrate via epigenetic-dependent differentiation of eTregs.”
BackgroundGut-microbiota derived bioactive metabolites and their functions in host physiology
Debnath, N., Kumar, R., Kumar, A., Mehta, P. K., & Yadav, A. K. (2021) · Biotechnology and Genetic Engineering Reviews · doi:10.1080/02648725.2021.1989847 · Cited by 77
Targeting the Gut Microbiome to Mitigate Immunotherapy-Induced Colitis in Cancer
Chang, A. E., Golob, J. L., Schmidt, T. M., Peltier, D. C., Lao, C. D., & Tewari, M. (2021) · Trends in Cancer · doi:10.1016/j.trecan.2021.02.005 · Cited by 62
Seth, R. K., Kimono, D., Alhasson, F., Sarkar, S., Albadrani, M., Lasley, S. K., Horner, R., Janulewicz, P., Nagarkatti, M., Nagarkatti, P., et al. (2018) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2018.05.006 · Cited by 55
Høgh, R. I., Møller, S. H., Jepsen, S. D., Mellergaard, M., Lund, A., Pejtersen, M., Fitzner, E., Andresen, L., & Skov, S. (2020) · The FASEB Journal · doi:10.1096/fj.202000162r · Cited by 56
Yan, Y., Ren, S., Duan, Y., Lu, C., Niu, Y., Wang, Z., Inglis, B., Ji, W., Zheng, Y., & Si, W. (2021) · npj Biofilms and Microbiomes · doi:10.1038/s41522-021-00242-3 · Cited by 51
Maltz, R. M., Keirsey, J., Kim, S. C., Mackos, A. R., Gharaibeh, R. Z., Moore, C. C., Xu, J., Bakthavatchalu, V., Somogyi, A., & Bailey, M. T. (2018) · PLOS ONE · doi:10.1371/journal.pone.0196961 · Cited by 51
Microbiota Modulation of Myeloid Cells in Cancer Therapy
Goldszmid, R. S., Dzutsev, A., Viaud, S., Zitvogel, L., Restifo, N. P., & Trinchieri, G. (2015) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-14-0225 · Cited by 46
Stanisavljević, S., Čepić, A., Bojić, S., Veljović, K., Mihajlović, S., Đedović, N., Jevtić, B., Momčilović, M., Lazarević, M., Mostarica Stojković, M., et al. (2019) · Scientific Reports · doi:10.1038/s41598-018-37505-7 · Cited by 43
Tyagi, P., Tasleem, M., Prakash, S., & Chouhan, G. (2020) · Food Research International · doi:10.1016/j.foodres.2020.109489 · Cited by 42
Gut microbial metabolites in cancer therapy
Song, P., Peng, Z., & Guo, X. (2025) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2024.06.016 · Cited by 38
Gut Microbiota–Host Interactions in Inborn Errors of Immunity
Castagnoli, R., Pala, F., Bosticardo, M., Licari, A., Delmonte, O. M., Villa, A., Marseglia, G. L., & Notarangelo, L. D. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22031416 · Cited by 34
“Short-chain fatty acids (SCFA) like butyrate can induce gene expression changes and imprint an antimicrobial program in macrophages [19,20], and can drive monocyte-to-macrophage differentiation via histone deacetylase (HDAC) inhibition [21].”
BackgroundMicrobial factors in inflammatory diseases and cancers
Ong, H. S., & Yim, H. C. H. (2017) · Advances in experimental medicine and biology · doi:10.1007/978-981-10-5987-2_7 · Cited by 29
Qu, Y., An, K., Wang, D., Yu, H., Li, J., Min, Z., Xiong, Y., Xue, Z., & Mao, Z. (2025) · Molecular Neurobiology · doi:10.1007/s12035-025-04726-7 · Cited by 30
A review of mathematical modeling of bone remodeling from a systems biology perspective
Cook, C. V., Lighty, A. M., Smith, B. J., & Ford Versypt, A. N. (2024) · Frontiers in Systems Biology · doi:10.3389/fsysb.2024.1368555 · Cited by 25
Prebiotics in atopic dermatitis prevention and management
Lee, Y. H., Verma, N. K., & Thanabalu, T. (2021) · Journal of Functional Foods · doi:10.1016/j.jff.2021.104352 · Cited by 19
Zhao, J., Hu, J., & Ma, X. (2021) · Nutrients · doi:10.3390/nu13082756 · Cited by 17
Yasir, M., Alkhaldy, A. A., Soliman, S. A., Turkistani, S. A., & Azhar, E. I. (2023) · Foods · doi:10.3390/foods12183342 · Cited by 16
Flegiel, E., Piotrowska, M., Ptasznik, M., Baran, A., Lenart, J., Podrażka, M., Mazurek, J., Stachowicz, H., Bartos, W., & Adamczyk, M. (2024) · Prospects in Pharmaceutical Sciences · doi:10.56782/pps.229 · Cited by 8
Commensal microbiota-derived signals regulate host immune system through epigenetic modifications
Takahashi, D., & Hase, K. (2015) · Inflammation and Regeneration · doi:10.2492/inflammregen.35.129 · Cited by 3
Metadata
- Authors
- Singh, N., Gurav, A., Sivaprakasam, S., Brady, E., Padia, R., Shi, H., Thangaraju, M., Prasad, P. D., Manicassamy, S., Munn, D. H., Lee, J. R., Offermanns, S., & Ganapathy, V.
- Affiliations
- Augusta University (US)
- Charlie Norwood VA Medical Center (US)
- Max Planck Institute for Heart and Lung Research (DE)
- Corresponding author
- Singh, Nagendra
- Ganapathy, Vadivel
- ORCID
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2014-01
- Volume
- 40
- Issue
- 1
- Pages
- 128-139
- ISSN
- 1074-7613 (ISSN-L)
- PMC
- PMC4305274
- OpenAlex
- W1981266729
- Cited by
- 2,368
- References
- 48
- Citations by year
- 2026: 230 · 2025: 242 · 2024: 252 · 2023: 266 · 2022: 237 · 2021: 268 · 2020: 193 · 2019: 172 · 2018: 136 · 2017: 122 · 2016: 97 · 2015: 97 · 2014: 54
- FWCI
- 50.60
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- Funders
- National Cancer Institute (R21CA152396, R01CA096651, CA152396, R01CA103320)
- National Institute of Allergy and Infectious Diseases (AI085440, R21AI085440)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK103576, R01DK097271)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Keywords
- GPR109A, butyrate, nicotinic acid, colonic inflammation, colon cancer, gut microbiota, dietary fiber, regulatory T cells, IL-10, IL-18, colonic epithelium, colitis, dendritic cells, macrophages
- MeSH terms
- Animals, Butyrates, Cell Differentiation, Cells, Cultured, Colitis, Colon, Colonic Neoplasms, Dendritic Cells, Disease Susceptibility, Epithelial Cells, Lymphocyte Activation, Macrophages, Mice, Inbred C57BL, Niacin, Receptors, Nicotinic, Signal Transduction, T-Lymphocyte Subsets, Interleukin-10, Mice, Knockout, Interleukin-18, Receptors, G-Protein-Coupled, T-Lymphocytes, Regulatory, Mice, Carcinogenesis, Microbiota
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