Gut Microbial Metabolites Fuel Host Antibody Responses
Open accessAbstract
Antibody production is a metabolically demanding process that is regulated by gut microbiota, but the microbial products supporting B cell responses remain incompletely identified. We report that short-chain fatty acids (SCFAs), produced by gut microbiota as fermentation products of dietary fiber, support host antibody responses. In B cells, SCFAs increase acetyl-CoA and regulate metabolic sensors to increase oxidative phosphorylation, glycolysis, and fatty acid synthesis, which produce energy and building blocks supporting antibody production. In parallel, SCFAs control gene expression to express molecules necessary for plasma B cell differentiation. Mice with low SCFA production due to reduced dietary fiber consumption or microbial insufficiency are defective in homeostatic and pathogen-specific antibody responses, resulting in greater pathogen susceptibility. However, SCFA or dietary fiber intake restores this immune deficiency. This B cell-helping function of SCFAs is detected from the intestines to systemic tissues and conserved among mouse and human B cells, highlighting its importance.
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Microbial metabolites can be utilized by T cells for their metabolic demand to enhance glycolysis and oxidative phosphorylation.
“Since microbial metabolites can be utilized by T cells for their metabolic demand to enhance glycolysis and oxidative phosphorylation28,29”
From Microbial short-chain fatty acids modulate CD8+ T cell responses and improve adoptive immunotherapy for cancer (2021) · cites this paper as [28]
SCFAs modulate B-cell energy metabolism to promote antibody production.
“Intriguingly, they further found that SCFAs in parallel modulate the energy metabolism of B cells to promote production of antibodies (M. Kim et al., 2016).”
From Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System (2017) · cites this paper as M. Kim et al., 2016
SCFAs support antibody responses by regulating gene expression through HDAC inhibition.
“Kim et al. shed further light on this observation and demonstrated that SCFAs support antibody responses by regulating gene expression through HDAC inhibition.”
From Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System (2017) · cites this paper as M. Kim et al., 2016
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“We also found that genes involved in B cell differentiation and function, such as Hepatitis A virus cellular receptor 1 (HAVcr-1)/T-cell immunoglobulin and mucin domain 1 (TIM-1), microphthalmia-associated transcription factor (Mitf), CD27, and LAPTM5 (Lin et al., 2004; Ouchida et al., 2010; Xiao et al., 2015; Xiao et…”
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“We also found that genes involved in B cell differentiation and function, such as Hepatitis A virus cellular receptor 1 (HAVcr-1)/T-cell immunoglobulin and mucin domain 1 (TIM-1), microphthalmia-associated transcription factor (Mitf), CD27, and LAPTM5 (Lin et al., 2004; Ouchida et al., 2010; Xiao et al., 2015; Xiao et…”
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“Indeed, others observed that C4 or other HDAC inhibitors at such high concentrations can suppress B cells or kill T cells in vitro (White et al., 2014; Zimmerman et al., 2012).”
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“AMPK activation suppresses the mTOR pathway (Green et al., 2011; Limon and Fruman, 2012).”
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“DISCUSSION The current paradigm for the function of gut microbiota in supporting antibody responses is mediated through TLR-activating bacterial DNA, proteins, and cell wall components, which directly and/or indirectly promote antibody responses (Kirkland et al., 2012; Teng et al., 2016).”
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“It is generally accepted that TLR ligands support antibody responses (Buchta and Bishop, 2014; Pone et al., 2012; Zeng et al., 2016).”
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“We also found that genes involved in B cell differentiation and function, such as Hepatitis A virus cellular receptor 1 (HAVcr-1)/T-cell immunoglobulin and mucin domain 1 (TIM-1), microphthalmia-associated transcription factor (Mitf), CD27, and LAPTM5 (Lin et al., 2004; Ouchida et al., 2010; Xiao et al., 2015; Xiao et…”
BackgroundPhospholipid biosynthesis program underlying membrane expansion during B-lymphocyte differentiation
Fagone, P., Sriburi, R., Ward-Chapman, C., Frank, M., Wang, J., Gunter, C., Brewer, J. W., & Jackowski, S. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m608175200 · Cited by 93 · cited 2× · see citing works
“Because FA synthesis is important for plasma B cell differentiation (Dufort et al., 2014; Fagone et al., 2007) and palmitic acid stimulates antibody production by B cells (Kunisawa et al., 2014), we examined lipid content in B cells treated with SCFAs.”
BackgroundRegulation of Intestinal IgA Responses by Dietary Palmitic Acid and Its Metabolism
Kunisawa, J., Hashimoto, E., Inoue, A., Nagasawa, R., Suzuki, Y., Ishikawa, I., Shikata, S., Arita, M., Aoki, J., & Kiyono, H. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1302944 · Cited by 75 · cited 2× · see citing works
“Because FA synthesis is important for plasma B cell differentiation (Dufort et al., 2014; Fagone et al., 2007) and palmitic acid stimulates antibody production by B cells (Kunisawa et al., 2014), we examined lipid content in B cells treated with SCFAs.”
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“We also found that genes involved in B cell differentiation and function, such as Hepatitis A virus cellular receptor 1 (HAVcr-1)/T-cell immunoglobulin and mucin domain 1 (TIM-1), microphthalmia-associated transcription factor (Mitf), CD27, and LAPTM5 (Lin et al., 2004; Ouchida et al., 2010; Xiao et al., 2015; Xiao et…”
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“It was observed many years ago that DF intake potentiates IgA responses in rats (Kudoh et al., 1998).”
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“These genes are linked to B cell differentiation and/or IgA and IgG production (Aldrich et al., 2003; Muramatsu et al., 2000; Turner et al., 1994).”
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“This activation induces the production of cytokines, retinoic acid (RA) and other B cell-activating molecules by various cell types (Gutzeit et al., 2014; Kim, 2013; Mora et al., 2006).”
BackgroundSelf-citation
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Gut microbiota-derived metabolites as key actors in inflammatory bowel disease
Lavelle, A., & Sokol, H. (2020) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-019-0258-z · Cited by 2,015 · see citing works
Short-chain fatty acids: Linking diet, the microbiome and immunity
Mann, E. R., Lam, Y. K., & Uhlig, H. H. (2024) · Nature reviews. Immunology · doi:10.1038/s41577-024-01014-8 · Cited by 1,595 · see citing works
SCFA: mechanisms and functional importance in the gut
Martin‐Gallausiaux, C., Marinelli, L., Blottière, H. M., Larraufie, P., & Lapaque, N. (2020) · Proceedings of The Nutrition Society · doi:10.1017/s0029665120006916 · Cited by 1,533 · see citing works
“Dietary fibres and SCFA enhance antibody response to bacteria by supporting B cell differentiation into plasma B cells via the increase of histone acetylation and of B cell metabolism((161,162)).”
BackgroundGut microbial metabolites as multi-kingdom intermediates
Krautkramer, K. A., Fan, J., & Bäckhed, F. (2021) · Nature Reviews Microbiology · doi:10.1038/s41579-020-0438-4 · Cited by 1,398 · see citing works
Metabolic Instruction of Immunity
Buck, M. D., Sowell, R., Kaech, S. M., & Pearce, E. L. (2017) · Cell · doi:10.1016/j.cell.2017.04.004 · Cited by 1,232 · see citing works
“…gut The metabolic relationship between commensals and immune cells in the gut is further illustrated by the finding that SCFAs derived from the fermentation of dietary fiber by gut microbiota promote B cell metabolism and boost antibody responses in both mouse and human B cells (Kim et al., 2016).”
Yang, W., Yu, T., Huang, X., Bilotta, A. J., Xu, L., Lu, Y., Sun, J., Pan, F., Zhou, J., Zhang, W., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-18262-6 · Cited by 1,060 · see citing works
Microbes, Metabolites, and the Gut-Lung Axis
Dang, A. T., & Marsland, B. J. (2019) · Mucosal Immunology · doi:10.1038/s41385-019-0160-6 · Cited by 1,028 · see citing works
Postler, T. S., & Ghosh, S. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.05.008 · Cited by 876 · see citing works
“Arpaia et al., 2013; Brown et al., 2003; Chang et al., 2014; Donohoe et al., 2012; Kalina et al., 2002; Kim et al., 2016; Le Poul et al., 2003; Macia et al., 2015; Maslowski et al., 2009; Millard et al., 2002; Nilsson et al., 2003; Singh et al., 2010; Smith et al., 2013; Thangaraju et al., 2009a,…”
BackgroundLuu, M., Riester, Z., Baldrich, A., Reichardt, N., Yuille, S., Busetti, A., Klein, M., Wempe, A., Leister, H., Raifer, H., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-24331-1 · Cited by 771 · see citing works
Trompette, A., Gollwitzer, E. S., Pattaroni, C., Lopez-Mejia, I. C., Riva, E., Pernot, J., Ubags, N., Fajas, L., Nicod, L. P., & Marsland, B. J. (2018) · Immunity · doi:10.1016/j.immuni.2018.04.022 · Cited by 678 · see citing works
“Acetyl-CoA produced during FAO can then fuel the OXPHOS and glycolytic pathways (Kim et al., 2016; Nsiah-Sefaa and McKenzie, 2016; van der Windt et al., 2012).”
BackgroundYang, W., & Cong, Y. (2021) · Cellular and Molecular Immunology · doi:10.1038/s41423-021-00661-4 · Cited by 701 · see citing works
Gut-Microbiota-Derived Metabolites Maintain Gut and Systemic Immune Homeostasis
Wang, J., Zhu, N., Su, L., Gao, Y., & Yang, R. (2023) · Cells · doi:10.3390/cells12050793 · Cited by 624 · see citing works
Gut microbiota-derived short-chain fatty acids and their role in human health and disease
Mukhopadhya, I., & Louis, P. (2025) · Nature Reviews Microbiology · doi:10.1038/s41579-025-01183-w · Cited by 586 · see citing works
“SCFAs have been shown to amplify antibody production by modulating gene expression, leading to a differentiation of B cells into specific plasma cells 91 .”
Luu, M., Pautz, S., Kohl, V., Singh, R., Romero, R., Lucas, S., Hofmann, J., Raifer, H., Vachharajani, N., Carrascosa, L. C., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-08711-2 · Cited by 508 · see citing works
Functions of Gut Microbiota Metabolites, Current Status and Future Perspectives
Liu, J., Tan, Y., Cheng, H., Zhang, D., Feng, W., & Peng, C. (2022) · Aging and disease · doi:10.14336/ad.2022.0104 · Cited by 529 · see citing works
“production of cecal sIgA and thus modulate the composition of gut microbiota [77].”
BackgroundInfluentialGill, P. A., van Zelm, M. C., Muir, J. G., & Gibson, P. R. (2018) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.14689 · Cited by 520 · see citing works
“leading to, increased glucose uptake, glycolytic activity and terminal differentiation into antibody-secreting plasma cells.(153) Such observa-”
BackgroundWu, W. H., Sun, M., Chen, F., Cao, A., Liu, H., Zhao, Y., Huang, X., Xiao, Y., Yao, S., Zhao, Q., et al. (2016) · Mucosal Immunology · doi:10.1038/mi.2016.114 · Cited by 500 · see citing works
“A recent report further demonstrated that SCFA promote intestinal IgA responses.(24) However, the mechanisms by which SCFA regulate intestinal IgA responses are still unknown.”
BackgroundResultGut microbiota influence immunotherapy responses: mechanisms and therapeutic strategies
(2022) · doi:10.1186/s13045-022-01273-9 · Cited by 495 · see citing works
“Finally, SCFAs provide energy for B-cell differentiation into plasma cells, antibody production, and overall changes in cell metabolism [95].”
BackgroundZeng, H., Umar, S., Rust, B., Lazarova, D., & Bordonaro, M. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20051214 · Cited by 480 · see citing works
“Furthermore, with strong HDAC inhibitory effects, butyrate not only increases B-cell production of antibodies but also promotes B-cell differentiation into plasma B-cells [125].”
BackgroundInfluentialChambers, E. S., Byrne, C. S., Morrison, D. J., Murphy, K. G., Preston, T., Tedford, C., Garcia-Perez, I., Fountana, S., Serrano-Contreras, J. I., Holmes, E., et al. (2019) · Gut · doi:10.1136/gutjnl-2019-318424 · Cited by 443 · see citing works
“24 To the best of our knowledge, this is the first evidence in vivo in humans that selectively increasing colonic propionate delivery increases circulating IgG levels and it would be of future interest to determine if this effect of IPE on adaptive immunity can decrease susceptibility to pathogen…”
BackgroundMontero, C. G., Fraile‐Μartinez, O., Gomez-Lahoz, A. M., Pekarek, L., Castellanos, A. J., Noguerales-Fraguas, F., Coca, S., Guijarro, L. G., García‐Honduvilla, N., Asúnsolo, Á., et al. (2021) · Nutrients · doi:10.3390/nu13020699 · Cited by 452 · see citing works
Dietary fiber and SCFAs in the regulation of mucosal immunity
Tan, J. K., Macia, L., & Mackay, C. R. (2022) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2022.11.007 · Cited by 427 · see citing works
Role of the gut microbiota in type 2 diabetes and related diseases
Yang, G., Wei, J., Liu, P., Zhang, Q., Tian, Y., Hou, G., Meng, L., Xin, Y., & Jiang, X. (2021) · Metabolism · doi:10.1016/j.metabol.2021.154712 · Cited by 418 · see citing works
Regulation of short-chain fatty acids in the immune system
Liu, X., Shao, J.-H., Liao, Y.-T., Wang, L., Yuan, J., Dong, P.-J., Liu, Z., He, D., Li, C., & Zhang, X. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1186892 · Cited by 435 · see citing works
Diet, Microbiota and Gut-Lung Connection
Anand, S., & Mande, S. S. (2018) · Frontiers in Microbiology · doi:10.3389/fmicb.2018.02147 · Cited by 409 · see citing works
“Multiple roles of SCFAs in energy and metabolism support activation/differentiation of B cells as well as production of antibodies (IgM/IgA; Supplementary Figure S1; Kim, 2016; Kim et al., 2016).”
BackgroundKim, C. H. (2023) · Cellular & Molecular Immunology · doi:10.1038/s41423-023-00987-1 · Cited by 420 · see citing works
“Thus, SCFAs and prebiotics appear to selectively increase the activity of regulatory lymphocytes, such as Tregs and Bregs, over in fl ammatory effector cells, such as Th17 cells and autoantibody-producing B cells.”
BackgroundInfluentialSelf-citationGut microbiota as the key controllers of “healthy” aging of elderly people
Ragonnaud, E., & Biragyn, A. (2021) · Immunity & Ageing · doi:10.1186/s12979-020-00213-w · Cited by 417 · see citing works
“By supporting differentiation of antibody-producing B cells, SCFAs increase both intestinal IgA and systemic IgG responses to combat pathogens [90].”
BackgroundControl of lymphocyte functions by gut microbiota-derived short-chain fatty acids
Kim, C. H. (2021) · Cellular & Molecular Immunology · doi:10.1038/s41423-020-00625-0 · Cited by 404 · see citing works
“SCFAs enhance the effect of the activation signals from B cell receptor and cytokine receptors when triggered by IL-5, IL-6, and IL-10.(45) While DF and SCFAs increase the production of IgG and IgA, they suppress IgE production.”
BackgroundInfluentialSelf-citationGonçalves, P., Araújo, J. R., & Santo, J. P. D. (2018) · Inflammatory Bowel Diseases · doi:10.1093/ibd/izx029 · Cited by 396 · see citing works
Immune regulation by microbiome metabolites
Kim, C. H. (2018) · Immunology · doi:10.1111/imm.12930 · Cited by 375 · see citing works
Self-citationThe 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
“also induce antibody response by stimulating intestinal mucosal IgA responses and systemic IgG responses.(105)”
BackgroundSanchez, H. N., Moroney, J. B., Gan, H., Shen, T., Im, J. L., Li, T., Taylor, J. R., Zan, H., & Casali, P. (2020) · Nature Communications · doi:10.1038/s41467-019-13603-6 · Cited by 369 · see citing works
Regulation of the Germinal Center Response
Stebegg, M., Kumar, S. D., Silva-Cayetano, A., Fonseca, V. R., Linterman, M. A., & Graca, L. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02469 · Cited by 349 · see citing works
“Microbial ATP controls Tfh cell differentiation (153) and short-chain fatty acids, a diverse group of bacterial metabolites, were shown to boost plasma cell differentiation and intestinal antibody production in PPs (162, 163).”
BackgroundPartners in Leaky Gut Syndrome: Intestinal Dysbiosis and Autoimmunity
Kinashi, Y., & Hase, K. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.673708 · Cited by 362 · see citing works
“” Commensal microbiota-derived metabolites have substantial impacts on host physiological functions through metabolic reprograming (64), epigenetic modifications (65), and the activation of specific receptors like G protein-coupled receptors (GPRs) and aryl hydrocarbon receptor (AhR).”
Backgroundvan der Beek, C. M., Dejong, C. H. C., Troost, F. J., Masclee, A., & Lenaerts, K. (2016) · Nutrition Reviews · doi:10.1093/nutrit/nuw067 · Cited by 345 · see citing works
Regulation of the effector function of CD8+ T cells by gut microbiota-derived metabolite butyrate
Luu, M., Weigand, K., Wedi, F., Breidenbend, C., Leister, H., Pautz, S., Adhikary, T., & Visekruna, A. (2018) · Scientific Reports · doi:10.1038/s41598-018-32860-x · Cited by 344 · see citing works
Rethinking mucosal antibody responses: IgM, IgG and IgD join IgA
Chen, K., Magri, G., Grasset, E. K., & Cerutti, A. (2020) · Nature reviews. Immunology · doi:10.1038/s41577-019-0261-1 · Cited by 339 · see citing works
Connecting the immune system, systemic chronic inflammation and the gut microbiome: the role of sex
Rizzetto, L., Fava, F., Tuohy, K. M., & Selmi, C. (2018) · Journal of Autoimmunity · doi:10.1016/j.jaut.2018.05.008 · Cited by 331 · see citing works
Mining the microbiota for microbial and metabolite-based immunotherapies
Skelly, A. N., Sato, Y., Kearney, S., & Honda, K. (2019) · Nature Reviews Immunology · doi:10.1038/s41577-019-0144-5 · Cited by 306 · see citing works
Epigenetic regulation by gut microbiota
Woo, V., & Alenghat, T. (2022) · Gut Microbes · doi:10.1080/19490976.2021.2022407 · Cited by 323 · see citing works
“Microbiota-derived SCFAs also supported intestinal B cell differentiation and antibody production by inhibiting HDAC activity leading to increased histone acetylation (H3K9Ac) and gene expression of multiple genes associated with B cell function.(93) Similar effects were observed in human and mouse B cells treated spe…”
BackgroundNey, 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
Gut Microbiota, Immune System, and Bone
D’Amelio, P., & Sassi, F. (2018) · Calcified Tissue International · doi:10.1007/s00223-017-0331-y · Cited by 315 · see citing works
“A recent study by Kim and colleagues suggests that GM may also affect B cells antibody production through SCFAs inhibition of HDAC and modulation of gene expression [49]; however, further studies are needed to clarify the”
BackgroundBridging intestinal immunity and gut microbiota by metabolites
Wang, G., Huang, S., Wang, Y., Cai, S., Yu, H., Liu, H., Zeng, X., Zhang, G., & Qiao, S. (2019) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-019-03190-6 · Cited by 299 · see citing works
“One study revealed that SCFAs are able to regulate B-cell gene expression via HDAC inhibition to promote antibody secretion, similar to the effect of SCFAs on other cells [157].”
BackgroundLynn, D. J., Benson, S. C., Lynn, M. A., & Pulendran, B. (2021) · Nature reviews. Immunology · doi:10.1038/s41577-021-00554-7 · Cited by 300 · see citing works
The impacts of natural polysaccharides on intestinal microbiota and immune responses – a review
Tang, C., Ding, R., Sun, J. G., Liu, J., Kan, J., & Jin, C. (2019) · Food & Function · doi:10.1039/c8fo01946k · Cited by 281 · see citing works
Chen, Y., Cui, W., Xiao, L., & Yang, H. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.761981 · Cited by 286 · see citing works
“SCFAs activate and release IL-18 through inflammasomes to maintain the integrity of the intestinal epithelium (38).”
BackgroundUnhealthy gut, unhealthy brain: The role of the intestinal microbiota in neurodegenerative diseases
Spielman, L. J., Gibson, D. L., & Klegeris, A. (2018) · Neurochemistry International · doi:10.1016/j.neuint.2018.08.005 · Cited by 266 · see citing works
“3-fold increase in cluster of differentiation (CD)20/CD38 B cells following stimulation with either acetate, propionate or butyrate (Kim et al., 2016).”
The nutrition‐gut microbiome‐physiology axis and allergic diseases
McKenzie, C. I., Tan, J., Macia, L., & Mackay, C. R. (2017) · Immunological Reviews · doi:10.1111/imr.12556 · Cited by 271 · see citing works
Adaptive immune education by gut microbiota antigens
Zhao, Q. S., & Elson, C. O. (2018) · Immunology · doi:10.1111/imm.12896 · Cited by 272 · see citing works
Gut microbiota influence in type 2 diabetes mellitus (T2DM)
Cunningham, A., Stephens, J. W., & Harris, D. A. (2021) · Gut Pathogens · doi:10.1186/s13099-021-00446-0 · Cited by 279 · see citing works
Gut Microbiota Features in Young Children With Autism Spectrum Disorders
Coretti, L., Paparo, L., Riccio, M. P., Amato, F., Cuomo, M., Natale, A., Borrelli, L., Corrado, G., De Caro, C., Comegna, M., et al. (2018) · Frontiers in Microbiology · doi:10.3389/fmicb.2018.03146 · Cited by 266 · see citing works
“With positive effects on brain functions and behavior of low doses of butyrate (<500 mg/kg) and stress-like response elicited by high doses of butyrate (>1,000 mg/kg) (Gagliano et al., 2014; Takuma et al., 2014; Kratsman et al., 2016).”
BackgroundGut microbiota in COVID-19: key microbial changes, potential mechanisms and clinical applications
Zhang, F., Lau, R. I., Liu, Q., Su, Q., Chan, F. K. L., & Ng, S. C. (2022) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-022-00698-4 · Cited by 275 · see citing works
Gut-Brain Psychology: Rethinking Psychology From the Microbiota–Gut–Brain Axis
Liang, S., Wu, X., & Jin, F. (2018) · Frontiers in Integrative Neuroscience · doi:10.3389/fnint.2018.00033 · Cited by 269 · see citing works
Zhang, Z., Tang, H., Chen, P., Xie, H., & Tao, Y. (2019) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-019-0074-5 · Cited by 251 · see citing works
Nutrients Mediate Intestinal Bacteria–Mucosal Immune Crosstalk
Ma, N., Guo, P., Zhang, J., He, T., Kim, S. W., Zhang, G., & Ma, X. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00005 · Cited by 249 · see citing works
Dietary Fibers from Fruits and Vegetables and Their Health Benefits via Modulation of Gut Microbiota
Cui, J., Lian, Y., Zhao, C., Du, H., Han, Y., Gao, W. Y., Xiao, H., & Zheng, J. (2019) · Comprehensive Reviews in Food Science and Food Safety · doi:10.1111/1541-4337.12489 · Cited by 243 · see citing works
The maintenance of memory plasma cells
Khodadadi, L., Cheng, Q., Radbruch, A., & Hiepe, F. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00721 · Cited by 232 · see citing works
“The metabolism of short-chain fatty acids (SCFAs) produced by gut microbiota are involved in plasma cell differentiation and promote antigen-specific host antibody responses (137).”
BackgroundHost- and Microbiota-Derived Extracellular Vesicles, Immune Function, and Disease Development
Macia, L., Nanan, R. K. H., Beheshti, E. H., & Grau, G. E. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms21010107 · Cited by 240 · see citing works
“While initially they were only considered as bacterial waste products, it is now established that SCFAs play a key role in the differentiation and function of most immune cells including anti-inflammatory regulatory T cells (Treg) [84,85], CD8+ T cells [86], macrophages [87,88], tolerogenic CD103+ dendritic cells [79,…”
BackgroundAcetate differentially regulates IgA reactivity to commensal bacteria
Takeuchi, T., Miyauchi, E., Kanaya, T., Kato, T., Nakanishi, Y., Watanabe, T., Kitami, T., Taida, T., Sasaki, T., Negishi, H., et al. (2021) · Nature · doi:10.1038/s41586-021-03727-5 · Cited by 232 · see citing works
Gut microbiome in type 1 diabetes: A comprehensive review
Zheng, P., Li, Z., & Zhou, Z. (2018) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.3043 · Cited by 229 · see citing works
“Recently, Kim and colleagues demonstrated that SCFAs regulated the energy metabolism of B cells in the gut, and promoted B cells differentiating into plasma cells and memory B cells through BCR‐ activating antigens, resulting in more IgG and IgA production.(80,81) Meanwhile, IgA can coat a substantial amount of gut mi…”
BackgroundDeehan, E. C., Duar, R. M., Armet, A. M., Pérez-Muñoz, M. E., Jin, M., & Walter, J. (2017) · Microbiology Spectrum · doi:10.1128/microbiolspec.bad-0019-2017 · Cited by 227 · see citing works
Yang, C., Mogno, I., Contijoch, E. J., Borgerding, J. N., Aggarwala, V., Li, Z., Siu, S., Grasset, E. K., Helmus, D. S., Dubinsky, M. C., et al. (2020) · Cell Host & Microbe · doi:10.1016/j.chom.2020.01.016 · Cited by 221 · see citing works
“ovatus (Kim et al., 2016), GF mice were administered heat-killed B.”
MethodBarrow, F., Khan, S., Fredrickson, G., Wang, H., Dietsche, K., Parthiban, P., Robert, S., Kaiser, T., Winer, S., Herman, A., et al. (2021) · Hepatology · doi:10.1002/hep.31755 · Cited by 210 · see citing works
Russo, E., Giudici, F., Fiorindi, C., Ficari, F., Scaringi, S., & Amedei, A. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.02754 · Cited by 204 · see citing works
“Plasma B cell differentiation could be promoted also by SCFAs, as they could modulate the gene expression that is necessary for antibody generation in a SCFAs receptor-independent manner (83).”
BackgroundThe regulation of gut mucosal IgA B-cell responses: recent developments
Lycke, N. Y., & Bemark, M. (2017) · Mucosal Immunology · doi:10.1038/mi.2017.62 · Cited by 201 · see citing works
“Interestingly, even microbial production of shortchain fatty acids from dietary fiber can stimulate broadly reactive SIgA antibodies in the gut.(155) IgA antibodies reactive to commensal bacteria are found in gut secretions, but not in serum, and it was, therefore, proposed that some SIgA antibodies are involved in co…”
BackgroundParticipation of Short-Chain Fatty Acids and Their Receptors in Gut Inflammation and Colon Cancer
Carretta, M. D., Quiroga, J., López‐Muñoz, R., Hidalgo, M. A., & Burgos, R. A. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.662739 · Cited by 201 · see citing works
“In this regard, research demonstrated that SCFAs promote intestinal IgA responses (Kim et al., 2016), and this role has been attributed in part to the FFAR2 receptor (Wu et al.”
BackgroundDeciphering the Chemical Lexicon of Host–Gut Microbiota Interactions
Nicolas, G. R., & Chang, P. V. (2019) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2019.04.006 · Cited by 195 · see citing works
“Alternatively, SCFAs were found to mediate proinflammatory effects by up-regulating B cell metabolism, which increases the systemic production of IgG and IgA to regulate both homeostatic and pathogen-specific immune responses [12].”
BackgroundPark, J., Wang, Q., Wu, Q., Mao‐Draayer, Y., & Kim, C. H. (2019) · Scientific Reports · doi:10.1038/s41598-019-45311-y · Cited by 197 · see citing works
Self-citationMagri, G., Comerma, L., Pybus, M., Sintes, J., Lligé, D., Segura-Garzón, D., Bascones, S., Yeste, A., Grasset, E. K., Gutzeit, C., et al. (2017) · Immunity · doi:10.1016/j.immuni.2017.06.013 · Cited by 194 · see citing works
“By degrading dietary polysaccharides into shortchain fatty acids with immunoregulatory and SIgA-inducing functions (Arpaia et al., 2013; Kim et al., 2016), these commensals may enhance protection against obesity and infection (Biddle et al.”
BackgroundDietary cellulose prevents gut inflammation by modulating lipid metabolism and gut microbiota
Kim, Y., Hwang, S. W., Kim, S., Lee, Y., Kim, T., Lee, S.-H., Kim, S. J., Yoo, H. J., Kim, E. N., & Kweon, M. (2020) · Gut Microbes · doi:10.1080/19490976.2020.1730149 · Cited by 192 · see citing works
“SCFAs can modulate the homeostasis of regulatory T (Treg) cells, plasma B cell differentiation, and antibody production.(11,12) Previous studies found that butyrate plays an important role in mammalian physiology, including serving as an energy source for gut epithelia and Treg generation.”
BackgroundElshahed, M. S., Miron, A., Aprotosoaie, A. C., & Farag, M. A. (2020) · Carbohydrate Polymers · doi:10.1016/j.carbpol.2020.117388 · Cited by 191 · see citing works
“They increased the expression of Xbp1 and Aicda genes and cellular metabolism in mouse and human B cells to aid and support the antibody production (Kim, Qie, Park, & Chang, 2016).”
BackgroundRegionalized Development and Maintenance of the Intestinal Adaptive Immune Landscape
Agace, W. W., & McCoy, K. D. (2017) · Immunity · doi:10.1016/j.immuni.2017.04.004 · Cited by 185 · see citing works
Short‐chain fatty acids: Bacterial messengers modulating the immunometabolism of T cells
Luu, M., & Visekruna, A. (2019) · European Journal of Immunology · doi:10.1002/eji.201848009 · Cited by 187 · see citing works
Wang, B., Zhang, L., Wang, Y., Dai, T., Qin, Z., Zhou, F., & Zhang, L. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-00986-0 · Cited by 185 · see citing works
“expression and supported optimal homeostatic and pathogenspecific antibody responses.(159) SCFAs have these effects on the B cells in the gut and systemic tissues.”
BackgroundRoles of the intestinal microbiota in pathogen protection
Úbeda, C., Djuković, A., & Isaac, S. (2017) · Clinical & Translational Immunology · doi:10.1038/cti.2017.2 · Cited by 180 · see citing works
Antibiotic-Induced Disruption of Gut Microbiota Alters Local Metabolomes and Immune Responses
Sun, L., Zhang, X., Zhang, Y., Zheng, K., Xiang, Q., Chen, N., Chen, Z., Zhang, N., Zhu, J., & He, Q. (2019) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2019.00099 · Cited by 183 · see citing works
Critical role of the gut microbiota in immune responses and cancer immunotherapy
Li, Z., Xiong, W., Zhu, L. W., Wang, J., Zeng, Z., Kołat, D., Li, X., Zhou, D., Xu, X., & Zhao, L.-Y. (2024) · Journal of Hematology & Oncology · doi:10.1186/s13045-024-01541-w · Cited by 188 · see citing works
“In addition, SCFAs increase acetyl-CoA levels to modulate energy metabolism in B cells to support antibody production [112].”
BackgroundLi, L., Wang, Y., Zhu, L., Liu, Z., Ye, C., & Qin, S. (2020) · Scientific Reports · doi:10.1038/s41598-020-58048-w · Cited by 177 · see citing works
The Role of the Gut Microbiota in the Pathogenesis of Diabetes
Bielka, W., Przezak, A., & Pawlik, A. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23010480 · Cited by 184 · see citing works
“These molecules can be considered as indicators of IR and predictors of diabetes mellitus development, because the serum metabolomes of patients suffering from IR or T2D contain an increased amount of BCAAs [38,39].”
BackgroundInfluentialGut microbiota composition is associated with SARS-CoV-2 vaccine immunogenicity and adverse events
Ng, S. C., Peng, Y., Zhang, L., Mok, C. K. P., Zhao, S., Li, A., Ching, J. Y. L., Liu, Y., Yan, S., Chan, D. L. S., et al. (2022) · Gut · doi:10.1136/gutjnl-2021-326563 · Cited by 177 · see citing works
Metabolic adaptations of tissue-resident immune cells
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- Authors
- Kim, M., Qie, Y., Park, J., & Kim, C. H.
- Affiliations
- Purdue University West Lafayette (US)
- Corresponding author
- Kim, Chang H.
- Venue
- Cell Host & Microbe
- Publisher
- Elsevier BV
- Published
- 2016-08
- Volume
- 20
- Issue
- 2
- Pages
- 202-214
- ISSN
- 1931-3128 (ISSN-L)
- PMC
- PMC4982788
- OpenAlex
- W2491805933
- Cited by
- 893
- References
- 59
- Citations by year
- 2026: 92 · 2025: 129 · 2024: 110 · 2023: 110 · 2022: 107 · 2021: 106 · 2020: 90 · 2019: 61 · 2018: 47 · 2017: 32 · 2016: 8
- FWCI
- 25.63
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Host & Microbe (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Seoul National University Open Repository (Seoul National University) (submittedVersion)
- Funders
- National Multiple Sclerosis Society
- Purdue University Center for Cancer Research
- National Institutes of Health
- National Cancer Institute (P30CA023168)
- National Institute of Allergy and Infectious Diseases (R01AI121302, R01AI080769, R01AI074745)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK076616)
- National Center for Research Resources (S10RR028293)
- 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 › Nursing › Nutrition and Dietetics › Microbial Metabolites in Food Biotechnology
- Keywords
- short-chain fatty acids, gut microbiota, antibody production, B cells, dietary fiber, acetyl-CoA, oxidative phosphorylation, glycolysis, fatty acid synthesis, plasma cell differentiation, immunodeficiency, microbial metabolites
- MeSH terms
- Gastrointestinal Microbiome, Animals, Antibody Formation, B-Lymphocytes, Cell Differentiation, Dietary Fiber, Fatty Acids, Volatile, Fermentation, Gene Expression Regulation, Mice, Inbred C57BL, Gastrointestinal Tract, Metabolic Networks and Pathways
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