The DOI matches its Crossref record; 59 of the 59 references it cites were found in a registry or an index.
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
Citations
Cites
Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells
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“A uthor M anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript comparable to the C3 levels created by HFD (Figure S2A).”
BackgroundInfluentialThe Microbial Metabolites, Short-Chain Fatty Acids, Regulate Colonic T reg Cell Homeostasis
Smith, P. M., Howitt, M. R., Panikov, N., Michaud, M., Gallini, C. A., Bohlooly-Y, M., Glickman, J. N., & Garrett, W. S. (2013) · Science · doi:10.1126/science.1241165 · Cited by 5,413 · cited 2×
“SCFAs increase colonic FoxP3+ Tregs (Furusawa et al., 2013; Smith et al., 2013).”
BackgroundRole of the microbiota in immunity and inflammation.
Belkaid, Y., & Hand, T. W. (2014) · Cell · doi:10.1016/j.cell.2014.03.011 · Cited by 5,385 · cited 1×
“A mounting body of evidence indicates that gut microbiota profoundly influences the host immune system (Alexander et al., 2014; Belkaid and Hand, 2014).”
BackgroundThe gut microbiota shapes intestinal immune responses during health and disease
Round, J. L., & Mazmanian, S. K. (2009) · Nature Reviews Immunology · doi:10.1038/nri2515 · Cited by 5,029 · cited 1×
“For example, germ-free mice are variably impaired in epithelial integrity, gut-associated lymphoid tissue development, innate and adaptive immunity, and immune tolerance (Round and Mazmanian, 2009).”
BackgroundMetabolites produced by commensal bacteria promote peripheral regulatory T-cell generation
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“SCFAs support epithelial cell integrity, innate immune functions, and the generation of regulatory and effector T cells (Arpaia et al., 2013; Furusawa et al., 2013; Kim et al., 2013; Park et al., 2015; Sakata, 1987; Schauber et al., 2003).”
BackgroundFunctional interactions between the gut microbiota and host metabolism
Tremaroli, V., & Bäckhed, F. (2012) · Nature · doi:10.1038/nature11552 · Cited by 4,387 · cited 2×
“…and analyzed data and drafted the manuscript with MK. anuscript A uthor M anuscript Keywords Short chain fatty acids; antibody; B cells; metabolism INTRODUCTION Host and gut microbial flora functionally interact in the gut for mutual benefits (Brown et al., 2013; Tremaroli and Backhed, 2012).”
BackgroundMuramatsu, M., Kinoshita, K., Fagarasan, S., Yamada, S., Shinkai, Y., & Honjo, T. (2000) · Cell · doi:10.1016/s0092-8674(00)00078-7 · Cited by 3,475 · cited 1×
“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).”
BackgroundShort chain fatty acids in human large intestine, portal, hepatic and venous blood
Cummings, J. H., Pomare, E. W., Branch, W. J., Naylor, C. P., & Macfarlane, G. T. (1987) · Gut · doi:10.1136/gut.28.10.1221 · Cited by 3,119 · cited 3×
“The total luminal SCFA concentration in humans reaches ~130 mmol/Kg in the colon and ~15 mmol/Kg in the small intestine (SI) (Cummings et al., 1987).”
BackgroundInfluentialEnergy contributions of volatile fatty acids from the gastrointestinal tract in various species
Bergman, E. N. (1990) · Physiological Reviews · doi:10.1152/physrev.1990.70.2.567 · Cited by 2,750 · cited 12×
“Moreover, SCFAs enhanced the mitochondrial ATP production and maximal respiration rates in B cells (Figure 4C).”
BackgroundMethodInfluentialRegulation of short-chain fatty acid production
Macfarlane, S., & Macfarlane, G. T. (2003) · Proceedings of the Nutrition Society · doi:10.1079/pns2002207 · Cited by 1,939 · cited 1×
“Short chain fatty acid (SCFAs) are the major microbial metabolites of DF (Macfarlane and Macfarlane, 2003).”
Background
Cited by
Sorted by citations
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
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
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 1,585
“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
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 1,270
“…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).”
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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