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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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“311,312 CRC biopsies revealed significantly increased immunity of B cells against commensal bacteria as well as C. albicans .”
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Gallou, S. L., Zhou, Z., Thai, L.-H., Fritzen, R., Aires, A. V. D. L., Megret, J., Yu, P., Kitamura, D., Bille, E., Tros, F., et al. (2018) · The Journal of Experimental Medicine · doi:10.1084/jem.20180977 · Cited by 45
“For what concerns B cells, short chain fatty acids, bacterial metabolites, or products of mucosal immune reactions has been described as global or antigen-specific modulators of IgA, IgM, or even IgG antibodies present in the general circulation (Proietti et al., 2014; Gomez de Agüero et al., 2016; Kim et al., 2016; Z…”
BackgroundMicrobial metabolite butyrate promotes induction of IL-10+IgM+ plasma cells
Föh, B., Buhre, J. S., Lunding, H. B., Moreno‐Fernandez, M. E., König, P., Sina, C., Divanovic, S., & Ehlers, M. (2022) · PLoS ONE · doi:10.1371/journal.pone.0266071 · Cited by 46
“Inhibition of HDACs by SCFAs may provide an underlying mechanism in their studies [39].”
BackgroundMicrobe-metabolite-host axis, two-way action in the pathogenesis and treatment of human autoimmunity
Meng, X. L., Zhou, H., Shen, H., Lufumpa, E., Li, X., Guo, B., & Li, B. (2019) · Autoimmunity Reviews · doi:10.1016/j.autrev.2019.03.006 · Cited by 46
Gut microbiota analysis for prediction of clinical relapse in Crohn’s disease
Buffet‐Bataillon, S., Bouguen, G., Fleury, F., Cattoir, V., & Cunff, Y. L. (2022) · Scientific Reports · doi:10.1038/s41598-022-23757-x · Cited by 47
Airway microbiome-immune crosstalk in chronic obstructive pulmonary disease
Kayongo, A., Robertson, N. M., Siddharthan, T., Ntayi, M. L., Ndawula, J. C., Sande, O. J., Bagaya, B. S., Kirenga, B., Mayanja‐Kizza, H., Joloba, M. L., et al. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1085551 · Cited by 50
The gut-lung axis in influenza A: the role of gut microbiota in immune balance
Ou, G., Xu, H., Wu, J., Wang, S., Chen, Y., Deng, L., & Chen, X. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1147724 · Cited by 49
“Moreover, inadequate production of SCFAs by GM compromises the differentiation of B cells into pathogen-speci fi c antibody-producing plasma cells (71).”
BackgroundYang, W., Yu, T., Liu, X., Yao, S., Khanipov, K., Golovko, G., Olivares–Villagómez, D., & Cong, Y. (2024) · Gut Microbes · doi:10.1080/19490976.2024.2363020 · Cited by 44
“6 Accumulating evidence indicates that gut microbiota antigen-specific CD4 + T cells are essential in regulating intestinal inflammation and maintaining intestinal homeostasis.”
BackgroundRole of the microbiome in regulation of the immune system
Kim, S., Ndwandwe, C., Devotta, H., Kareem, L., Yao, L., & O’Mahony, L. (2025) · Allergology International · doi:10.1016/j.alit.2024.12.006 · Cited by 55
The Gut Microbiota: How Does It Influence the Development and Progression of Liver Diseases
Kanmani, P., Kanmani, S., & Kim, H. (2020) · Biomedicines · doi:10.3390/biomedicines8110501 · Cited by 44
“The SCFA also assists in the activation and differentiation of B cells and the production of IgM and IgA antibodies [27].”
BackgroundAyakdaş, G., & Ağagündüz, D. (2023) · Heliyon · doi:10.1016/j.heliyon.2023.e19888 · Cited by 47
“A higher consumption of SCFAs or MACs relieves this immune deficiency and lowers the severity of inflammation [89,90].”
BackgroundGut microbial metabolites in cancer immunomodulation
Liu, H., Xiong, X., Zhu, W., Wang, S., Huang, W.-C., Zhu, G., Xu, H., & Yang, L. (2025) · Molecular Cancer · doi:10.1186/s12943-025-02521-5 · Cited by 52
Iida, N., Mizukoshi, E., Yamashita, T., Terashima, T., Arai, K., Seishima, J., & Kaneko, S. (2019) · International Journal of Cancer · doi:10.1002/ijc.32339 · Cited by 44
“of B cells to plasma cells, which generate IgA type antibodies.(39) Blautia is abundant in the gut of healthy people, but not in the gut of older persons and patients with various diseases, including Type 2 diabetes, liver cirrhosis and colon cancer.”
BackgroundOpportunities and Challenges of the Human Microbiome in Ovarian Cancer
Cheng, H., Wang, Z., Cui, L., Wen, Y. L., Chen, X., Gong, F., & Yi, H. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.00163 · Cited by 45
Qu, D., Sun, F., Feng, S., Yu, L., Tian, F., Zhang, H., Chen, W., & Zhai, Q. (2021) · Food & Function · doi:10.1039/d1fo03073f · Cited by 44
Cross-talk between signal transduction and metabolism in B cells
Jellusova, J. (2018) · Immunology Letters · doi:10.1016/j.imlet.2018.11.003 · Cited by 44
Technological tools and strategies for culturing human gut microbiota in engineered in vitro models
Sardelli, L., Perottoni, S., Tunesi, M., Boeri, L., Fusco, F., Petrini, P., Albani, D., & Giordano, C. (2021) · Biotechnology and Bioengineering · doi:10.1002/bit.27816 · Cited by 43
“…has physicochemical peculiarities influencing bacterial composition and strain abundance (Arrieta & Finlay, 2012; Boeri et al., 2019; Chambers et al., 2015; Conlon & Bird, 2015; Keshavarzian et al., 2012; Kim et al., 2014, 2016; Manach et al., 2004; Morrison & Preston, 2016; Stokholm et al., 2016).”
BackgroundRole of metabolites derived from gut microbiota in inflammatory bowel disease
Zheng, L., Wen, X., & Duan, S.-L. (2022) · World Journal of Clinical Cases · doi:10.12998/wjcc.v10.i9.2660 · Cited by 43
Microbiota and epigenetics: promising therapeutic approaches?
El-Sayed, A., Aleya, L., & Kamel, M. S. (2021) · Environmental Science and Pollution Research · doi:10.1007/s11356-021-15623-6 · Cited by 43
“Microbiota also aids in the regulation of the production of other immunoglobulins (Kim et al. 2016; Ubeda et al. 2017).”
BackgroundGill, P. A., Muir, J. G., Gibson, P. R., & van Zelm, M. C. (2022) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/nqac246 · Cited by 44
“Indeed, SCFAs are potent at inducing Ig class– switched B-cell subsets in animal models (34, 35).”
BackgroundJirsova, Z., Heczková, M., Daňková, H., Malínská, H., Videnska, P., Vespalcová, H., Micenková, L., Bartoňová, L., Sticová, E., Lodererová, A., et al. (2019) · BioMed Research International · doi:10.1155/2019/7084734 · Cited by 41
Ganesan, R., Gupta, H., Gebru, Y. A., Youn, G. S., Choi, Y. R., Kim, H. S., Yoon, S. J., Kim, D. J., Kim, T., & Suk, K. T. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22031160 · Cited by 42
Tang, B., Tang, L., He, W., Jiang, X., Hu, C.-J., Li, Y., Zhang, Y., Pang, K., Lei, Y., Li, S., et al. (2022) · Cell Reports Medicine · doi:10.1016/j.xcrm.2022.100752 · Cited by 42
“A previous study has demonstrated that SCFAs activate B cell metabolism and promote antibody responses in a mouse model of Citrobacter rodentium infection.(50) A recent study has observed that microbial-derived SCFAs improve the humoral immune response to seasonal influenza vaccine.”
Zhang, S., Hu, H., He, W., Muhammad, Z., Wang, L., Liu, F., & Pan, S. (2019) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201801363 · Cited by 40
The Metabolomics of Childhood Atopic Diseases: A Comprehensive Pathway-Specific Review
Schjødt, M. S., Gürdeniz, G., & Chawes, B. (2020) · Metabolites · doi:10.3390/metabo10120511 · Cited by 44
“They are reported to have several anti-inflammatory properties, including inducing regulatory T cells in mice [64–66], production of prostaglandin E2 [67], altering the function of dendritic cells [68], inhibition of histone deacetylase activity [69], limiting eosinophil trafficking and promotion [70], and survival of…”
BackgroundThe Role of Microbiota-Derived Vitamins in Immune Homeostasis and Enhancing Cancer Immunotherapy
Gholami, H., Chmiel, J. A., Burton, J. P., & Vareki, S. M. (2023) · Cancers · doi:10.3390/cancers15041300 · Cited by 40
“Antibiotic-treated patients with advanced solid tumors displayed reduced survival rates and poor ICI responses, which were associated with reduced gut microbiota diversity and abundance [56,263,265].”
BackgroundIntestinal barrier dysfunction as a key driver of severe COVID-19
Tsounis, E. P., Triantos, C. K., Konstantakis, C., Marangos, M. N., & Assimakopoulos, S. F. (2023) · World Journal of Virology · doi:10.5501/wjv.v12.i2.68 · Cited by 39
Yao, H., Wang, L., Tang, X., Yang, Z., Li, H.-Y., Sun, C., Wu, X.-Y., & Xu, D. (2020) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2020.05.121 · Cited by 35
Thiruvengadam, M., Subramanian, U., Venkidasamy, B., Thirupathi, P., Samynathan, R., Shariati, M. A., Ребезов, М. Б., Chung, I., & Rengasamy, K. R. R. (2021) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2021.1954874 · Cited by 40
Ghassab, F. T., Mahmoudi, F. S., Tinjani, R. T., Meibodi, A. E., Zali, M. R., & Yadegar, A. (2024) · Life Sciences · doi:10.1016/j.lfs.2024.122748 · Cited by 40
Engineered Bacteria for Disease Diagnosis and Treatment Using Synthetic Biology
Jin, K., Huang, Y. B., Che, H., & Wu, Y. (2025) · Microbial Biotechnology · doi:10.1111/1751-7915.70080 · Cited by 53
Çebi, M., & Yilmaz, Y. N. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1575770 · Cited by 42
“These effects are mediated by HDAC inhibition, which alters gene expression related to B cell differentiation (104, 105).”
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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