Microbiota-Derived Metabolites Suppress Arthritis by Amplifying Aryl-Hydrocarbon Receptor Activation in Regulatory B Cells
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The differentiation of IL-10-producing regulatory B cells (Bregs) in response to gut-microbiota-derived signals supports the maintenance of tolerance. However, whether microbiota-derived metabolites can modulate Breg suppressive function remains unknown. Here, we demonstrate that rheumatoid arthritis (RA) patients and arthritic mice have a reduction in microbial-derived short-chain fatty acids (SCFAs) compared to healthy controls and that in mice, supplementation with the SCFA butyrate reduces arthritis severity. Butyrate supplementation suppresses arthritis in a Breg-dependent manner by increasing the level of the serotonin-derived metabolite 5-Hydroxyindole-3-acetic acid (5-HIAA), which activates the aryl-hydrocarbon receptor (AhR), a newly discovered transcriptional marker for Breg function. Thus, butyrate supplementation via AhR activation controls a molecular program that supports Breg function while inhibiting germinal center (GC) B cell and plasmablast differentiation. Our study demonstrates that butyrate supplementation may serve as a viable therapy for the amelioration of systemic autoimmune disorders.
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Butyrate restricts inflammation by promoting the differentiation of Treg cells and supporting the functions of regulatory B cells.
“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 [706]
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“They regulate B cells for effective humoral immune responses and generate Bregs [42, 85].”
BackgroundImmunosuppressive Mechanisms of Regulatory B Cells
Catalán, D., Mansilla, M. A., Ferrier, A., Soto, L., Oļeiņika, K., Aguillón, J. C., & Aravena, O. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.611795 · Cited by 407 · see citing works
The Immunomodulatory Functions of Butyrate
Siddiqui, M. T., & Cresci, G. A. (2021) · Journal of Inflammation Research · doi:10.2147/jir.s300989 · Cited by 381 · see citing works
“butyrate to have anti-inflammatory properties resulting from induction of IL-10 producing B cells.(101,102) However, conflicting data exist, as other studies which”
ResultNey, L.-M., Wipplinger, M., Grossmann, M., Engert, N., Wegner, V. D., & Mosig, A. S. (2023) · Open Biology · doi:10.1098/rsob.230014 · Cited by 337 · see citing works
The Gut Microbiota at the Service of Immunometabolism
Michaudel, C., & Sokol, H. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2020.09.004 · Cited by 321 · see citing works
One year in review 2021: pathogenesis of rheumatoid arthritis
Testa, D., Calvacchi, S., Petrelli, F., Giannini, D., Bilia, S., Alunno, A., & Puxeddu, I. (2021) · Clinical and Experimental Rheumatology · doi:10.55563/clinexprheumatol/j1l5l3 · Cited by 314 · see citing works
Tryptophan Metabolism as a Pharmacological Target
Modoux, M., Rolhion, N., Mani, S., & Sokol, H. (2020) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2020.11.006 · Cited by 285 · see citing works
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Crosstalk between Gut Microbiota and Host Immunity: Impact on Inflammation and Immunotherapy
Campbell, C., Kandalgaonkar, M. R., Golonka, R. M., Yeoh, B. S., Vijay–Kumar, M., & Saha, P. (2023) · Biomedicines · doi:10.3390/biomedicines11020294 · Cited by 256 · see citing works
“, serotonin-derived metabolite 5-hydroxyindole-3-acetic acid, where AhR activation supported regulatory B cell function [356].”
BackgroundHe, J., Chu, Y., Li, J., Meng, Q., Liu, Y., Jin, J., Wang, Y., Wang, J., Huang, B., Shi, L., et al. (2022) · Science Advances · doi:10.1126/sciadv.abm1511 · Cited by 233 · see citing works
“Thus, our data demonstrated the multiple efficiency of butyrate in protecting from joint deformity, consistent with the results of a previous study ( 28 ).”
Leveraging diet to engineer the gut microbiome
Wolter, M., Grant, E. T., Boudaud, M., Steimle, A., Pereira, G. V., Martens, E. C., & Desai, M. S. (2021) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-021-00512-7 · Cited by 211 · see citing works
Gut microbiota and rheumatoid arthritis: From pathogenesis to novel therapeutic opportunities
Zhao, T., Wei, Y., Zhu, Y., Xie, Z., Hai, Q., Li, Z., & Qin, D. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1007165 · Cited by 235 · see citing works
“Besides, several metabolites including short-chain fatty acids, serotonin, as well as plant enzymes in the gut can also influence RA (45).”
BackgroundDesign of synthetic human gut microbiome assembly and butyrate production
Clark, R. L., Connors, B., Stevenson, D. M., Hromada, S. E., Hamilton, J. J., Amador‐Noguez, D., & Venturelli, O. S. (2021) · Nature Communications · doi:10.1038/s41467-021-22938-y · Cited by 197 · see citing works
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“Additionally, a recent study revealed that feacal level of butyrate was significantly reduced during the remission phase of RA [67].”
BackgroundThe Current and Future Perspectives of Postbiotics
Liang, B., & Xing, D. (2023) · Probiotics and Antimicrobial Proteins · doi:10.1007/s12602-023-10045-x · Cited by 217 · see citing works
“found that the bacterial metabolite butyrate “relays” on regulatory B cell (Breg) activation and suppresses rheumatoid arthritis (RA) [71].”
BackgroundAdrenergic regulation of immune cell function and inflammation
Sharma, D., & Farrar, J. D. (2020) · Seminars in Immunopathology · doi:10.1007/s00281-020-00829-6 · Cited by 196 · see citing works
Ageing of the gut microbiome: Potential influences on immune senescence and inflammageing
Conway, J., & Duggal, N. A. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101323 · Cited by 194 · see citing works
The aryl hydrocarbon receptor as a mediator of host-microbiota interplay
Dong, F., & Perdew, G. H. (2020) · Gut Microbes · doi:10.1080/19490976.2020.1859812 · Cited by 193 · see citing works
“Building on these findings, a significant increase in microbiota-induced AHR ligand 5-hydroxyindole-3-acetic acid (5-HIAA), metabolized from serotonin, was discovered to attenuate arthritis with butyrate supplementation by promoting IL10 transcription in B cells in an AHRdependent manner.(42)”
BackgroundInfluentialGut microbiota bridges dietary nutrients and host immunity
Fan, L., Xia, Y., Wang, Y., Han, D., Liu, Y., Li, J., Fu, J., Wang, L., Gan, Z., Liu, B., et al. (2023) · Science China Life Sciences · doi:10.1007/s11427-023-2346-1 · Cited by 197 · see citing works
“Contrarily, SCFAs, the well-studied SFAs, have been shown to have protective effects on inflammation and health via modulating gut microbiota (Li et al., 2019a; Rosser et al., 2020).”
BackgroundWorby, C. J., Schreiber, H. L., Straub, T. J., van Dijk, L. R., Bronson, R. A., Olson, B. S., Pinkner, J. S., Obernuefemann, C. L. P., Muñoz, V. L., Paharik, A. E., et al. (2022) · Nature Microbiology · doi:10.1038/s41564-022-01107-x · Cited by 188 · see citing works
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Jansen, K., Cevhertas, L., Ma, S.-Y., Satitsuksanoa, P., Akdiş, M., & van de Veen, W. (2021) · Allergy. European Journal of Allergy and Clinical Immunology · doi:10.1111/all.14763 · Cited by 149 · see citing works
GPR35 promotes neutrophil recruitment in response to serotonin metabolite 5-HIAA
Giovanni, M. D., Tam, H., Valet, C., Xu, Y., Looney, M. R., & Cyster, J. G. (2022) · Cell · doi:10.1016/j.cell.2022.01.010 · Cited by 170 · see citing works
Psoriatic arthritis from a mechanistic perspective
Schett, G., Rahman, P., Ritchlin, C., Mcinnes, I., Elewaut, D., & Scher, J. (2022) · Nature Reviews Rheumatology · doi:10.1038/s41584-022-00776-6 · Cited by 159 · see citing works
Yu, D., Du, J., Pu, X., Zheng, L., Chen, S., Wang, N., Li, J., Chen, S., Pan, S., & Shen, B. (2022) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2021.763507 · Cited by 169 · see citing works
“The adjuvant-induced arthritis rat model demonstrated that Enterococcus_faecium could enhance the anti-inflammatory and antiarthritic effects of methotrexate (Rovensky et al., 2005).”
BackgroundPerinatal and Early-Life Nutrition, Epigenetics, and Allergy
Acevedo, N., Alhamwe, B. A., Caraballo, L. R., Ding, M., Ferrante, A., Garn, H., Garssen, J., Hii, C. S. T., Irvine, J., Llinás-Caballero, K., et al. (2021) · Nutrients · doi:10.3390/nu13030724 · Cited by 172 · see citing works
Short-chain fatty acid: An updated review on signaling, metabolism, and therapeutic effects
Rekha, K., Venkidasamy, B., Samynathan, R., Nagella, P., Ребезов, М. Б., Khayrullin, M., Ponomarev, E., Bouyahya, A., Sarkar, T., Shariati, M. A., et al. (2022) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2022.2124231 · Cited by 166 · see citing works
“…effectively increases serotonin-derived metabolite, which in turn activates AhR, which supports Breg function and thereby inhibits B-cell and plasmablast differentiation and ultimately suggests that butyrate supplementation ameliorates systemic autoimmune diseases (Rosser et al. 2020).”
BackgroundAshique, S., Rubis, G. D., Sirohi, E., Mishra, N., Rihan, M., Garg, A., Reyes, R.-J., Manandhar, B., Bhatt, S., Jha, N. K., et al. (2022) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2022.110231 · Cited by 171 · see citing works
The role of short-chain fatty acids in inflammatory skin diseases
Xiao, X., Hu, X., Yao, J., Cao, W., Zou, Z., Wang, L., Qin, H., Zhong, D., Li, Y., Xue, P., et al. (2023) · Frontiers in Microbiology · doi:10.3389/fmicb.2022.1083432 · Cited by 163 · see citing works
Gut microbiota derived bile acid metabolites maintain the homeostasis of gut and systemic immunity
Su, L., Gao, Y., & Yang, R. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1127743 · Cited by 167 · see citing works
Visekruna, A., & Luu, M. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.703218 · Cited by 164 · see citing works
Zou, F., Qiu, Y., Huang, Y., Zou, H., Xiao, C., Niu, Q., Luo, A., & Sun, J. (2021) · Cell Death and Disease · doi:10.1038/s41419-021-03880-9 · Cited by 155 · see citing works
Zhao, J., Bai, M., Ning, X., Qin, Y., Wang, Y., Yu, Z., Dong, R., Zhang, Y., & Sun, S. (2022) · Journal of the American Society of Nephrology · doi:10.1681/asn.2022020189 · Cited by 153 · see citing works
Microbiota-derived butyrate regulates intestinal inflammation: Focus on inflammatory bowel disease
Couto, M. R., Gonçalves, P., Magro, F., & Martel, F. (2020) · Pharmacological Research · doi:10.1016/j.phrs.2020.104947 · Cited by 148 · see citing works
Modoux, M., Rolhion, N., Lefèvre, J. H., Oeuvray, C., Nádvorník, P., Illéš, P., Emond, P., Parc, Y. R., Mani, S., Dvořák, Z., et al. (2022) · Gut Microbes · doi:10.1080/19490976.2022.2105637 · Cited by 145 · see citing works
“This seems logical as acetate is typically released into the bloodstream via the portal vein and reaches the liver, while butyrate is primarily absorbed and metabolized by the colonic epithelium.32 Butyrate has recently been suggested to be an AhR ligand according to in silico molecular modeling.17 However, using radi…”
BackgroundInfluentialThe Role of Diet and Gut Microbiota in Regulating Gastrointestinal and Inflammatory Disease
Gill, P. A., Inniss, S., Kumagai, T., Rahman, F. Z., & Smith, A. M. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.866059 · Cited by 149 · see citing works
Microbiota-derived tryptophan metabolites in vascular inflammation and cardiovascular disease
Paeslack, N., Mimmler, M., Becker, S., Gao, Z., Khuu, M. P., Mann, A., Malinarich, F., Regen, T., & Reinhardt, C. (2022) · Amino Acids · doi:10.1007/s00726-022-03161-5 · Cited by 139 · see citing works
“Microbiota-derived metabolites were demonstrated to protect from autoimmune disease development (Rosser et al. 2020).”
BackgroundGut 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 145 · see citing works
“It achieves this by increasing the concentration of the tryptophan-derived metabolite 5-hydroxyindole-3-acetic acid, which activates the AhR [18].”
BackgroundGut microbiota in pre-clinical rheumatoid arthritis: From pathogenesis to preventing progression
Lin, L., Zhang, K., Xiong, Q., Zhang, J., Cai, B., Huang, Z., Yang, B., Wei, B., Chen, J., & Niu, Q. (2023) · Journal of Autoimmunity · doi:10.1016/j.jaut.2023.103001 · Cited by 138 · see citing works
Du, H., Yue, S.-Y., Niu, D., Liu, C., Zhang, L., Chen, J., Chen, Y., Guan, Y., Hua, X., Li, C., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.915218 · Cited by 132 · see citing works
“Among these gut-microbiota-derived metabolites, SCFAs have emerged as important microbial metabolites participating in the modulation of immune inflammation and metabolism by interactions with both gut microbiome and host receptors (18).”
BackgroundNascimento, D. C., Viacava, P. R., Ferreira, R. G., Damaceno, M. A., Piñeros, A. R., Melo, P. H., Donate, P. B., Toller-Kawahisa, J. E., Zoppi, D., Veras, F. P., et al. (2021) · Immunity · doi:10.1016/j.immuni.2021.08.005 · Cited by 129 · see citing works
Differential Roles of IDO1 and IDO2 in T and B Cell Inflammatory Immune Responses
Merlo, L. M. F., DuHadaway, J. B., Montgomery, J. D., Peng, W., Murray, P. J., Prendergast, G. C., Caton, A. J., Muller, A. J., & Mandik‐Nayak, L. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01861 · Cited by 120 · see citing works
Matei, D. E., Menon, M., Alber, D., Smith, A. M., Nedjat-Shokouhi, B., Fasano, A., Magill, L., Duhlin, A., Bitoun, S., Gleizes, A., et al. (2021) · Med · doi:10.1016/j.medj.2021.04.013 · Cited by 119 · see citing works
Self-citationShort 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 121 · see citing works
Altered intestinal microbiome and metabolome correspond to the clinical outcome of sepsis
Sun, S., Wang, D., Dong, D., Xu, L., Xie, M., Wang, Y., Ni, T., Jiang, W., Zhu, X., Ning, N., et al. (2023) · Critical Care · doi:10.1186/s13054-023-04412-x · Cited by 117 · see citing works
“Some bacteria directly metabolize tryptophan, while others produce short-chain fatty acids (SCFAs) that modify the microbial structure and thereby indirectly facilitate tryptophan metabolism [48, 49, 51].”
BackgroundInfluentialYao, Y., Cai, X. T., Zheng, Y., Zhang, M., Fei, W., Sun, D., Zhao, M., Ye, Y., & Zheng, C. (2022) · British Journal of Pharmacology · doi:10.1111/bph.15852 · Cited by 118 · see citing works
“We note a recent study showing that microbiota-derived metabolites suppress arthritis by amplifying aryl-hydrocarbon receptor activation in regulatory B cells (Rosser et al., 2020).”
BackgroundMethodInfluentialHuang, K., Han, Y., Chen, Y., Shen, H., Zeng, S., & Cai, C. (2025) · Molecular Cancer · doi:10.1186/s12943-024-02205-6 · Cited by 116 · see citing works
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 112 · see citing works
“…also been found that SCFAs, mainly butyrate, can also modulate the body’s immune function by interacting with the aryl hydrocarbon receptor (AHR) [13], whereas Alex [14] confirmed the ability of propionate and butyrate to stimulate angiopoietin-like protein 4 (ANGPTL) by interacting with…”
BackgroundRomero-Figueroa, M. D. S., Ramírez‐Durán, N., Montiel-Jarquín, Á. J., & Horta‐Baas, G. (2023) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2023.1092118 · Cited by 107 · see citing works
“In the antigen-induced model of arthritis (AIA), in stool samples, there was a reduction of butyrate and acetate levels during the acute and remission phase of arthritis compared to pre-arthritic mice (Rosser et al., 2020).”
BackgroundResultInfluentialChang, S.-C., Shen, M., Liu, C., Pu, C., Hu, J., & Huang, C. (2020) · Oncology Letters · doi:10.3892/ol.2020.12190 · Cited by 105 · see citing works
Role of short‐chain fatty acids in host physiology
Liu, M., Lu, Y., Xue, G., Han, L., Jia, H., Wang, Z., Zhang, J., Liu, P., Yang, C., & Zhou, Y. (2024) · Animal Models and Experimental Medicine · doi:10.1002/ame2.12464 · Cited by 112 · see citing works
The Rising Era of “Immunoporosis”: Role of Immune System in the Pathophysiology of Osteoporosis
Srivastava, R., & Sapra, L. (2022) · Journal of Inflammation Research · doi:10.2147/jir.s351918 · Cited by 79 · see citing works
Emerging targetome and signalome landscape of gut microbial metabolites
Zheng, X., Cai, X., & Hao, H. (2022) · Cell Metabolism · doi:10.1016/j.cmet.2021.12.011 · Cited by 100 · see citing works
Fecal microbiota transplantation: Emerging applications in autoimmune diseases
Yang, R., Chen, Z., & Cai, J. (2023) · Journal of Autoimmunity · doi:10.1016/j.jaut.2023.103038 · Cited by 97 · see citing works
Dürholz, K., Hofmann, J., Iljazović, A., Häger, J., Lucas, S., Sarter, K., Strowig, T., Bang, H., Rech, J., Schett, G. A., et al. (2020) · Nutrients · doi:10.3390/nu12103207 · Cited by 96 · see citing works
Tan, Y.-Q., Wang, Y., Feng, H.-Y., Guo, Z.-Y., Li, X., Nie, X.-L., & Zhao, Y. (2022) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2022.03.025 · Cited by 97 · see citing works
Wang, Z., Liu, J., Li, F., Luo, Y., Ge, P., Zhang, Y., Wen, H., Yang, Q., Ma, S., & Chen, H. (2022) · Pharmacological Research · doi:10.1016/j.phrs.2022.106321 · Cited by 96 · see citing works
B Cell–Directed Therapy in Autoimmunity
Abeles, I. Y., Palma, C., Meednu, N., Payne, A. S., Looney, R. J., & Anolik, J. H. (2023) · Annual Review of Immunology · doi:10.1146/annurev-immunol-083122-044829 · Cited by 95 · see citing works
Cytokine production by human B cells: role in health and autoimmune disease
de Gruijter, N. M., Jebson, B. R., & Rosser, E. C. (2022) · Clinical & Experimental Immunology · doi:10.1093/cei/uxac090 · Cited by 90 · see citing works
“…or short-chain fatty acids butyrate and acetate are associated with the production of IL-10 by CD19 + CD24 hi CD38 hi transitional B cells (55) and CD24 hi CD27 + B10 cells (56). t e However, this has not been the only study to demonstrate that metabolic stimuli are associated with the…”
BackgroundSelf-citationTie, Y., Huang, Y., Chen, R., Li, L., Chen, M., & Zhang, S. (2023) · Gut Microbes · doi:10.1080/19490976.2023.2265028 · Cited by 92 · see citing works
The aryl hydrocarbon receptor: structure, signaling, physiology and pathology
Coumoul, X., Barouki, R., Esser, C., Haarmann‐Stemmann, T., Lawrence, B. P., Lehmann, J., Moura‐Alves, P., Murray, I. A., Opitz, C. A., Perdew, G. H., et al. (2026) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02500-8 · Cited by 103 · see citing works
“54 – 57 There is growing interest in developing targeted therapies that modulate AHR activity, potentially opening new avenues for medical intervention in autoimmune diseases such as rheumatoid arthritis, 58 chronic in fl ammatory skin disorders 59 and cardiovascular and pulmonary diseases.”
Modulating AHR function offers exciting therapeutic potential in gut immunity and inflammation
Chen, Y., Wang, Y., Fu, Y., Yin, Y., & Xu, K. (2023) · Cell & Bioscience · doi:10.1186/s13578-023-01046-y · Cited by 91 · see citing works
Gut-derived acetate promotes B10 cells with antiinflammatory effects
Daïen, C., Tan, J., Audo, R., Mielle, J., Quek, L., Krycer, J. R., Angelatos, A. S., Duraes, M., Pinget, G. V., Ni, D., et al. (2021) · JCI Insight · doi:10.1172/jci.insight.144156 · Cited by 87 · see citing works
“Indeed, a previous report on the induction of splenic B10 cell by butyrate was shown to be an indirect effect by promoting the serotonin-derived metabolite 5-hydroxyindole-3-acetic acid (20).”
Wang, R., Li, B., Huang, B., Li, Y., Liu, Q., Lyu, Z., Chen, R., Qian, Q., Liang, X. S., Pu, X., et al. (2024) · Gastroenterology · doi:10.1053/j.gastro.2024.05.014 · Cited by 87 · see citing works
Bahman, F., Choudhry, K., Al‐Rashed, F., Al‐Mulla, F., Sindhu, S. T. A. K., & Ahmad, R. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1421346 · Cited by 98 · see citing works
“Butyrate supplements improved arthritis in mice by altering microbiota and favoring the production of 5-hydroxyindole-3-acetic acid (5-HIAA), a serotonin-derived metabolite that reduces the severity of arthritis (168).”
BackgroundLiu, Y., Zhou, Q., Ye, F., Yang, C., & Jiang, H. (2023) · Neoplasia · doi:10.1016/j.neo.2023.100928 · Cited by 86 · see citing works
Munteanu, C., & Schwartz, B. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25158250 · Cited by 86 · see citing works
“Furthermore, butyrate has been reported to promote regulatory B cells and inhibit the formation of germinal centers and plasmablasts, thereby reducing the severity of antigen-induced arthritis in mice [182].”
BackgroundThe bridge of the gut–joint axis: Gut microbial metabolites in rheumatoid arthritis
Xu, X., Wang, M., Wang, Z., Chen, Q., Chen, X., Xu, Y., Dai, M., Wu, B., & Li, Y. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1007610 · Cited by 85 · see citing works
“Taken together, the findings show that SCFAs may regulate immune balance through the Treg/IL-10/ Th17 axis (131) or B cells (133).”
BackgroundInfluentialRannug, A. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21165681 · Cited by 82 · see citing works
Gut microbiota and allergic diseases in children
Akagawa, S., & Kaneko, K. (2022) · Allergology International · doi:10.1016/j.alit.2022.02.004 · Cited by 87 · see citing works
The emerging role of microbiota-derived short-chain fatty acids in immunometabolism
Jasim, S. A., Opulencia, M. J. C., Ramírez‐Coronel, A. A., Abdelbasset, W. K., Abed, M. H., Markov, A. A., Al‐Awsi, G. R. L., Shamsiev, J. A., Hammid, A. T., Shalaby, M. N., et al. (2022) · International Immunopharmacology · doi:10.1016/j.intimp.2022.108983 · Cited by 84 · see citing works
Schiweck, C., Thanarajah, S. E., Aichholzer, M., Matura, S., Reif, A., Vrieze, E., Weigert, A., & Visekruna, A. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23158272 · Cited by 79 · see citing works
“A recent study assessing levels of SCFAs in blood and stool of patients has shown reduced levels of SCFAs in patients with RA compared to controls, although diverging effects were detected for serum and stool concentrations and per study [62,63].”
BackgroundProbiotics ameliorate alveolar bone loss by regulating gut microbiota
Jia, L., Tu, Y., Jia, X., Du, Q., Zheng, X. M., Yuan, Q., Zheng, L., Zhou, X., & Xu, X. (2021) · Cell Proliferation · doi:10.1111/cpr.13075 · Cited by 77 · see citing works
“Promoting gut-derived SCFAs generation has shown protective effects in multiple diseases including IBS, cardiovascular diseases, Alzheimer’s disease and rheumatoid arthritis[58, 64-66].”
BackgroundYang, Y., Zhang, Y., Song, J., Li, Y., Zhou, L., Xu, H., Wu, K., Gao, J., Zhao, M., & Zheng, Y. (2023) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2023.127335 · Cited by 77 · see citing works
Osteoimmunology: The Crosstalk between T Cells, B Cells, and Osteoclasts in Rheumatoid Arthritis
Yang, M., & Zhu, L. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25052688 · Cited by 88 · see citing works
“Previous reports have indicated an inverse correlation between the frequency of CD19 + CD24 hi CD38 hi B cells, which harbor the highest proportion of IL-10 + Bregs, and the clinical severity of RA [83].”
BackgroundResultTrend, S., Leffler, J., Jones, A. P., Cha, L., Gorman, S., Brown, D. A., Breit, S. N., Kermode, A. G., French, M. A., Ward, N. C., et al. (2021) · Scientific Reports · doi:10.1038/s41598-021-84881-8 · Cited by 75 · see citing works
Circadian Host-Microbiome Interactions in Immunity
Butler, T. D., & Gibbs, J. E. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01783 · Cited by 74 · see citing works
“Recent work has uncovered a mechanism whereby bacteria derived butyrate enhances production of 5-HIAA which acts via AhR to support regulatory B cell function (70).”
BackgroundCrossing the barriers: Revisiting the gut feeling in rheumatoid arthritis
Brandl, C., Bucci, L., Schett, G. A., & Zaiss, M. M. (2021) · European Journal of Immunology · doi:10.1002/eji.202048876 · Cited by 75 · see citing works
Du, W., Jiang, S., Yin, S., Wang, R., Zhang, C., Yin, B., Li, J., Li, L., Qi, N., Zhou, Y. Q., et al. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2400385121 · Cited by 78 · see citing works
“Since 5 - HIAA was recently suggested to activate the AhR signaling in regulatory B cells ( 28 ), we sought to examine whether 5 - HIAA acts as a ligand to activate hepatic AhR and the downstream signaling.”
Rheumatoid arthritis and oxidative stress, a review of a decade
Zamudio-Cuevas, Y. E., Martínez‐Flores, K., Martínez‐Nava, G. A., Clavijo‐Cornejo, D., Fernández‐Torres, J., & Sánchez‐Sánchez, R. (2022) · Cellular and Molecular Biology · doi:10.14715/cmb/2022.68.6.28 · Cited by 74 · see citing works
“In this regard, studies in mice have shown that supplementation with short-chain fatty acids, and in particular butyrate, has an immunosuppressive effect on RA (64).”
BackgroundInfluentialThe emerging field of regulatory B cell immunometabolism
Rosser, E. C., & Mauri, C. (2021) · Cell Metabolism · doi:10.1016/j.cmet.2021.05.008 · Cited by 73 · see citing works
Self-citationOsteometabolism: Metabolic Alterations in Bone Pathologies
Srivastava, R. K., Sapra, L., & Mishra, P. K. (2022) · Cells · doi:10.3390/cells11233943 · Cited by 72 · see citing works
Intestinal Dysbiosis and Tryptophan Metabolism in Autoimmunity
Brown, J., Robusto, B. A., & Morel, L. M. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01741 · Cited by 67 · see citing works
“In support of this hypothesis, the short chain fatty acid butyrate has been shown to increase the production of 5-HIAA from serotonin, which promotes Breg cell function through AhR and ameliorates murine autoimmune arthritis (85).”
BackgroundModulation of Immune Responses by Nutritional Ligands of Aryl Hydrocarbon Receptor
de Juan, A., & Segura, É. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.645168 · Cited by 69 · see citing works
“Gavage with 5-HIAA increases the expression of Il10 in spleen B cells and reduces the severity of joint swelling in a model of antigen-induced arthritis (13).”
BackgroundInfluentialGut Microbiota and Chemical-Induced Acute Liver Injury
Chen, T., Li, R., & Chen, P. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.688780 · Cited by 69 · see citing works
“Studies have demonstrated that SCFAs can affect the differentiation of B cells and maintain the homeostasis of intestinal T cells (Scott et al., 2018; Rosser et al., 2020).”
BackgroundMicrobiome-immune interactions in tuberculosis
Mori, G., Morrison, M., & Blumenthal, A. (2021) · PLoS Pathogens · doi:10.1371/journal.ppat.1009377 · Cited by 77 · see citing works
Xie, R., & Zhang, Y. (2022) · Prostaglandins Leukotrienes and Essential Fatty Acids · doi:10.1016/j.plefa.2022.102530 · Cited by 66 · see citing works
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“Furthermore, studies have demonstrated that butyrate supplementation effectively reduces arthritis severity in animal models by modulation of regulatory B cells 42 .”
Ding, T., Su, R. J., Wu, R., Xue, H., Wang, Y., Su, R., Gao, C., Li, X., & Wang, C. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.641013 · Cited by 64 · see citing works
“Butyrate activates transcriptional marker aryl-hydrocarbon receptor (AhR) in a manner dependent on 5-Hydroxyindole-3acetic acid (5-HIAA) and therethrough indirectly supports CD19CD21CD24Breg cell function (77).”
BackgroundAryl hydrocarbon receptor: The master regulator of immune responses in allergic diseases
Riaz, F., Pan, F., & Wei, P. Y. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1057555 · Cited by 65 · see citing works
“Additionally, the activation of the Ahr is activated by microbiota-derived butyrate, which helps in the accumulation of Il-10-secreting regulatory B cells (Bregs) (174, 175).”
BackgroundA new paradigm for a new simple chemical: butyrate & immune regulation
Dang, G., Wu, W., Zhang, H., & Everaert, N. (2021) · Food & Function · doi:10.1039/d1fo02116h · Cited by 64 · see citing works
- Authors
- Rosser, E. C., Piper, C. J. M., Matei, D. E., Blair, P. A., Rendeiro, A. F., Orford, M., Alber, D. G., Krausgruber, T., Catalan, D., Klein, N., Manson, J. J., Drozdov, I., Bock, C., Wedderburn, L. R., Eaton, S., & Mauri, C.
- Affiliations
- Great Ormond Street Hospital (GB)
- University College London (GB)
- Austrian Academy of Sciences (AT)
- University College Hospital (GB)
- Corresponding author
- Rosser, Elizabeth C.
- Mauri, Claudia
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2020-04
- Volume
- 31
- Issue
- 4
- Pages
- 837-851.e10
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC7156916
- OpenAlex
- W3013317600
- Cited by
- 579
- References
- 75
- Citations by year
- 2026: 73 · 2025: 103 · 2024: 112 · 2023: 104 · 2022: 88 · 2021: 70 · 2020: 27
- FWCI
- 23.50
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Universidad de Chile (submittedVersion, cc-by-nc-nd)
- Funders
- Weizmann Institute of Science
- Albert-Ludwigs-Universität Freiburg
- Bill and Melinda Gates Foundation
- Versus Arthritis (21140, 21141, 21593)
- Manchester Biomedical Research Centre
- Rosetrees Trust (M536)
- NIHR Bristol Biomedical Research Centre
- 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 › Rheumatology › Rheumatoid Arthritis Research and Therapies
- Keywords
- rheumatoid arthritis, regulatory B cells, gut microbiota, short-chain fatty acids, butyrate, aryl hydrocarbon receptor, 5-hydroxyindoleacetic acid, serotonin metabolism, germinal center B cells, plasmablast differentiation, IL-10, autoimmune disease therapy, dietary supplementation
- MeSH terms
- Gastrointestinal Microbiome, Animals, Arthritis, Rheumatoid, Butyrates, Cells, Cultured, Fatty Acids, Volatile, Female, Humans, Hydroxyindoleacetic Acid, Male, Mice, Inbred C57BL, Middle Aged, Receptors, Aryl Hydrocarbon, Mice, Basic Helix-Loop-Helix Proteins, B-Lymphocytes, Regulatory
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