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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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“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]
In the citing paper
“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
In the citing paper
“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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“…and stabilization of the hypoxia-inducible factor (HIF) signaling pathway (Shen et al., 2017) in a ligand-receptor interaction by regulating epithelial homeostasis and stimulating anti-tumor immune activity (Trompette et al., 2014; Kim et al., 2016; Zou et al., 2018; Matsushita et al., 2021).”
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“Additionally, SCFAs boost mTOR activation and glycolytic activity, further facilitating B cell activation and differentiation into antibody-secreting cells (Kim et al., 2016).”
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“Butyrate promotes host antibody responses [64], intestinal IgA secretion [65], and modulation of CD8 + T cell responses [66].”
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“Furthermore, shortchain fatty acids, products of the fermentation of dietary fibers by intestinal microbiota, can augment systemic IgG responses through regulating gene expression for plasma B cell differentiation and increasing cellular metabolism as well as boosting glycolytic activity in B cells (37).”
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“…of in fl ammatory cytokines (IL-6, IL-8, and tumor necrosis factor - a (TNF-a )) (115, 116), and stimulating the production of anti-in fl ammatory cytokines such as IL-10 by peripheral blood mononuclear cells (PBMCs) (117) which could suppresses pro-in fl ammatory types of Th17 and Th2 cells in turn.”
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“Additionally, SCFAs influenced the expression of genes linked to B-cell differentiation (activation-induced cytidine deaminase (Aic-da)/(AID), X-box binding protein 1 (Xbp1), and PR domain zinc finger protein 1 (prdm1)) by inhibiting HDAC [38].”
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“In addition, gut microbiota stimulates the maturation of the mucosal innate immune system (Hooper et al., 2012; Tremaroli and B€ackhed, 2012; Kim et al., 2016) and regulates immune homeostasis by several different mechanisms (Artis, 2008; Slack et al.”
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“Like in T cells, SCFAs can also drive the differentiation of intestinal IgA + plasma cells by activating GPCRs on the B cell surface and through epigenetic regulation via the inhibition of HDAC activity (63, 64).”
Ahmad, S., Ali, S., Rehman, D. A. U., Haq, I. U., Liaqat, I., Aftab, M. N., & Shume, T. (2026) · Journal of Medical Microbiology · doi:10.1099/jmm.0.002117 · Cited by 21
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InfluentialGut instincts in neuroimmunity from the eighteenth to twenty-first centuries
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“SCFAs influence plasma cell differentiation and antibody production [87, 88], where acetate induces IgA production and butyrate suppresses IgA production [89, 90].”
BackgroundMetabolic Contributions to Pathobiology of Asthma
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“SCFAs are an important of energy for intestinal epithelial cells and can promote antibody response by affecting B cell energy metabolism, such as lipid metabolism, glycolysis, and oxidative phosphorylation [178].”
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“maintenance of energy metabolism homeostasis (20).”
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“Therefore, SCFAs effectively improve innate and acquired immune responses through microbial fermentation (Kim et al., 2016).”
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“It is reported that metabolites (acetate and propionate) produced by genus Succiniclasticum and Akkermansia can promote Ig A and Ig G response in humans and mice (Kim et al. 2016).”
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“…e s o n B c e ll e p i g e n e t i c s , c l a ss s w i t c h i n g , a n t i b o d y r e s p o n s e s , a n d d i ff e r e n t i a t i o n [ 107 , 108 ] B c e ll s I m p l i c a t e d i n M S , n e u r o m y e l i t i s o p t i c a s p e c t r u m d i s o r d e r , M O G a n t i b o d y - a ss o…”
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“Furthermore, butyrate can promote the memory potential and antiviral cytotoxic effector functions of CD8 T cells (Bachem et al. 2019), and B cell differentiation and secretion of IgA and IgG antibodies (Kim et al. 2016).”
Ko, H., Kim, C. J., Choi, S., Noh, J., Kim, S. W., Lee, J., Byun, S., Lee, H., Park, J. C., Park, H. E., et al. (2026) · Microbiome · doi:10.1186/s40168-025-02284-7 · Cited by 17
“6G) [50].”
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Chen, Y., Wang, Z., Chen, X., Chao, G., & Zhang, S. (2023) · Journal of Applied Microbiology · doi:10.1093/jambio/lxad032 · Cited by 16
Mechanistic insights into the interaction between the host gut microbiome and malaria
Mandal, R. K., & Schmidt, N. W. (2023) · PLoS Pathogens · doi:10.1371/journal.ppat.1011665 · Cited by 16
Lipid metabolism in B cell biology
Peeters, R., & Jellusova, J. (2023) · Molecular Oncology · doi:10.1002/1878-0261.13560 · Cited by 15
“One study suggests that SCFAs boost B cell metabolism but also suppress HDAC activity and induce expression of genes necessary for PC differentiation [75].”
BackgroundMingxing, T., Wu, Y., Liang, J., Yang, S., Huang, Z., Hu, J., Yang, Q., Liu, F., & Li, S. (2024) · Frontiers in Microbiology · doi:10.3389/fmicb.2024.1457348 · Cited by 15
Mechanisms conferring multi-layered protection against intestinal Salmonella Typhimurium infection
Kroon, S., & Hardt, W. (2025) · FEMS Microbiology Reviews · doi:10.1093/femsre/fuaf038 · Cited by 14
“IgA, the predominant antibody in the intestinal lumen, is produced in response to the commensal microbiota upon TLR signalling and recognition of SCFAs (Slack et al. 2009 ; Hapfelmeier et al. 2010 ; Kim et al. 2016 ).”
Zhou, L., Zhang, W., Liu, Z., Xie, Y., & Jiang, K. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1697675 · Cited by 14
“B cells, which are central to humoral immunity, also exhibit metabolic shifts upon activation, transitioning from a reliance on oxidative phosphorylation to increased glycolysis to support antibody production (59, 60).”
Microbial metabolites in tumor epigenetic regulation
Zhang, W., Zhang, H., Liao, Y., Jiang, S., Zhang, H., Huang, C., Song, Z., Zhao, R., Lü, P., Kang, X., et al. (2026) · iMeta · doi:10.1002/imt2.70115 · Cited by 17
Gut microbiome changes in anti-N-methyl-D-aspartate receptor encephalitis patients
Jingya, W., Zhang, X., Yang, F., Shi, X., Wang, X., Chen, R., Du, F., Shi, M., & Jiang, W. (2022) · BMC Neurology · doi:10.1186/s12883-022-02804-0 · Cited by 14
“An imbalance of the gut microbiome can cause abnormal immune function, leading to the production of specific and non-specific antibodies [4, 9].”
BackgroundNishimoto, Y., Kawai, J., Mori, K., Hartanto, T., Komatsu, K., Kudo, T., & Fukuda, S. (2023) · Frontiers in Nutrition · doi:10.3389/fnut.2022.1078060 · Cited by 17
“Key exclusion criteria were as follows: (1) subjects who had a plan or who had taken medication within a month before the start of trial, which would affect the trial result; (2) subjects who regularly consumed food for specified health uses, food with function claims, supplements and/or health foods more than thrice…”
BackgroundChen, H., Jia, Z., He, M., Chen, A., Zhang, X., Xu, J., & Wang, C. (2023) · Microbiome · doi:10.1186/s40168-023-01616-9 · Cited by 14
“In addition, Faecalibacterium promotes the differentiation of T and B lymphocytes into plasma cells and increases the metabolism of T and B cells, thereby enhancing the production of host antibodies [49].”
BackgroundGorini, F., & Tonacci, A. (2023) · Antioxidants · doi:10.3390/antiox12101898 · Cited by 16
Variability of Vaccine Responsiveness in Young Children
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“The data could even be removed and stated Tmu was not recovered from any animal that was not directly inoculated with Tmu.”
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“They act as a significant source of energy to support cells when metabolized, as they can readily be converted into acetyl-CoA, fueling the tricarboxylic acid (TCA) cycle for ATP production [154,159,191].”
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Neijat, M., Habtewold, J. Z., Li, S., Jing, M.-Y., & House, J. D. (2020) · Prostaglandins Leukotrienes and Essential Fatty Acids · doi:10.1016/j.plefa.2020.102182 · Cited by 15
Ganesan, R., & Suk, K. T. (2022) · Livers · doi:10.3390/livers2030012 · Cited by 16
“IgA is more important for gut homeostasis maintenance [32].”
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“In mice with low SCFA due to decreased dietary fiber uptake or microbial insufficiency, homeostatic and pathogen-specific antibody responses became defective, resulting in greater pathogen susceptibility [45].”
Dey, P. (2025) · The FASEB Journal · doi:10.1096/fj.202502523rr · Cited by 16
Microbiota insights in endometriosis
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“The immune responses mediated by SCFAs consist of the regulation of Treg inhibition, histone-dea-cetylases, and B cells by regulation of the mitogen-activated protein kinases (MAPK) and mammalian target of rapamycin (mTOR) pathways [61].”
Immune communication between the intestinal microbiota and the cardiovascular system
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Therapeutic targeting of gut‐originating regulatory B cells in neuroinflammatory diseases
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“…TNF-α produced by DCs [109], the release of APRIL and BAFF [110], as well as dietary factors, including retinoic acid signaling [111, 112] and gut microbiota-produced short-chain fatty acids (SCFA) [113], enhance TGF-β R signaling and by this, promote the generation of IgA plasma cell responses.”
BackgroundDietary antioxidants and vascular calcification: From pharmacological mechanisms to challenges
Lian, Y., Li, Y., Liu, A., Ghosh, S., Shi, Y., & Huang, H. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.115693 · Cited by 13
Andreescu, M. (2023) · Cureus · doi:10.7759/cureus.50318 · Cited by 14
“Furthermore, the gut microbiota is capable of generating short-chain fatty acids that enhance immune cell function and amplify the effectiveness of antibiotics against bacterial infections [34].”
BackgroundNondigestible carbohydrates and gut microbiota: A dynamic duo in host defense
Zong, X., Luo, S., Liu, S., Deehan, E. C., Wang, Y., & Jin, M. (2024) · Animal Nutriomics · doi:10.1017/anr.2024.8 · Cited by 16
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“It has been shown that after feeding different doses of prebiotics to experimental mice, the levels of SCFAs and IgA in the intestines increased with the dose, as well as the levels of IgA and IgG in the serum of the mice, which suggests that SCFAs can affect the antibody levels throughout the host’s body.”
BackgroundInfluentialA review of the pathogenesis of epilepsy based on the microbiota-gut-brain-axis theory
Yang, W., Cui, H., Wang, C., Wang, X., Yan, C., & Cheng, W. (2024) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2024.1454780 · Cited by 15
“GM metabolites, such as SCFAs, influence immunoglobulin synthesis and secretion by regulating B lymphocyte differentiation (Honda and Littman, 2016; Kim et al., 2016).”
BackgroundChandra, S., & Vassar, R. J. (2024) · Immunological Reviews · doi:10.1111/imr.13412 · Cited by 17
“36,37 While SCFA have a clear influence on peripheral immunity in several contexts, the effect of SCFA on peripheral immunity has not been extensively investigated in AD models.”
Din, M. A. U., Lin, Y., Lyu, C., Yi, C., Fang, A., & Mao, F. (2025) · Molecular Medicine · doi:10.1186/s10020-024-01060-x · Cited by 13
“Additionally, B lymphocytes secrete immunoglobulin A (IgA) in response to SCFAs, providing an initial line of defense against pathogens that have infiltrated the body (Kim et al. 2016).”
Short‐chain fatty acids during pregnancy in multiple sclerosis: A prospective cohort study
Cuello, J. P., Ginés, M. L. M., García‐Domínguez, J. M., Velarde, A. T., Ros, A. L., Higueras, Y., Rivera, A. M., Briceño, H. G., Larroca, S. G., León-Luis, J. A. D., et al. (2021) · European Journal of Neurology · doi:10.1111/ene.15150 · Cited by 13
“Also, SCFAs can boost mucosal and systemic antibody responses during steady state or infection [12].”
BackgroundImpact of Dietary Fiber on West Nile Virus Infection
Ni, D., Tan, J., Niewold, P., Spiteri, A. G., Pinget, G. V., Stanley, D., King, N. J. C., & Macia, L. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.784486 · Cited by 13
“Dietary fiber and SCFA have a broad impact on the immune system by promoting the development of anti-inflammatory regulatory T cells (10) and regulatory B cells (11), of Th1 cells (12), of memory CD8 T cells (13, 14) and by increasing B cell antibody production (15).”
BackgroundOh, S.-Y., & Seo, H. (2023) · Heliyon · doi:10.1016/j.heliyon.2023.e15668 · Cited by 13
Soluble Fiber Use in Pediatric Short Bowel Syndrome: A Survey on Prevailing Practices
Harvie, M. L., Norris, M. A. T., & Sevilla, W. M. A. (2018) · Nutrition in Clinical Practice · doi:10.1002/ncp.10089 · Cited by 13
Metadata
- 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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