Cited by 897Gut microbiota and healthT-cell and B-cell ImmunologyMicrobial Metabolites in Food Biotechnology

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Gut Microbial Metabolites Fuel Host Antibody Responses

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Kim, Myunghoo, Qie, Yaqing, Park, Jeongho, Kim, Chang H.·2016·Cell Host & Microbe

DOI 10.1016/j.chom.2016.07.001PMC PMC4982788

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Abstract

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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Additional file 3 of XX sex chromosome complement modulates immune responses to heat-killed Streptococcus pneumoniae immunization in a microbiome-dependent manner
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Additional file 5 of XX sex chromosome complement modulates immune responses to heat-killed Streptococcus pneumoniae immunization in a microbiome-dependent manner
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Additional file 9 of XX sex chromosome complement modulates immune responses to heat-killed Streptococcus pneumoniae immunization in a microbiome-dependent manner
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Additional file 1 of XX sex chromosome complement modulates immune responses to heat-killed Streptococcus pneumoniae immunization in a microbiome-dependent manner
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Additional file 1 of The effects of exopolysaccharides and exopolysaccharide-producing Lactobacillus on the intestinal microbiome of zebrafish (Danio rerio)
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Additional file 3 of Interleukin-21 receptor signaling promotes metabolic dysfunction-associated steatohepatitis-driven hepatocellular carcinoma by inducing immunosuppressive IgA+ B cells
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Additional file 3 of Microbiota long-term dynamics and prediction of acute graft-versus-host disease in pediatric allogeneic stem cell transplantation
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Additional file 6 of XX sex chromosome complement modulates immune responses to heat-killed Streptococcus pneumoniae immunization in a microbiome-dependent manner
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Additional file 4 of The effects of exopolysaccharides and exopolysaccharide-producing Lactobacillus on the intestinal microbiome of zebrafish (Danio rerio)
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Additional file 8 of XX sex chromosome complement modulates immune responses to heat-killed Streptococcus pneumoniae immunization in a microbiome-dependent manner
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Additional file 4 of XX sex chromosome complement modulates immune responses to heat-killed Streptococcus pneumoniae immunization in a microbiome-dependent manner
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Additional file 7 of XX sex chromosome complement modulates immune responses to heat-killed Streptococcus pneumoniae immunization in a microbiome-dependent manner
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Additional file 2 of The effects of exopolysaccharides and exopolysaccharide-producing Lactobacillus on the intestinal microbiome of zebrafish (Danio rerio)
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Additional file 2 of XX sex chromosome complement modulates immune responses to heat-killed Streptococcus pneumoniae immunization in a microbiome-dependent manner
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Additional file 4 of Interleukin-21 receptor signaling promotes metabolic dysfunction-associated steatohepatitis-driven hepatocellular carcinoma by inducing immunosuppressive IgA+ B cells
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Additional file 1 of Interleukin-21 receptor signaling promotes metabolic dysfunction-associated steatohepatitis-driven hepatocellular carcinoma by inducing immunosuppressive IgA+ B cells
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Additional file 2 of Gut microbial features may influence antiviral IgG levels after vaccination against viral respiratory infectious diseases: the evidence from two-sample bidirectional mendelian randomization
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Additional file 2 of Interleukin-21 receptor signaling promotes metabolic dysfunction-associated steatohepatitis-driven hepatocellular carcinoma by inducing immunosuppressive IgA+ B cells
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Effects of clove extract and hydrolyzed whey peptides supplementation on health, performance and blood parameters of suckling dairy calves
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“During this window, the gastrointestinal tract, especially the small intestine, remains structurally and functionally immature, rendering neonatal calves highly susceptible to enteric disorders, metabolic instability, and systemic inflammation (Steele et al., 2016; Kim et al., 2016).”
Bifidobacterium breve PRL2020 mitigates antibiotic-induced gut symptoms and dysbiosis in children treated with amoxicillin or amoxicillin-clavulanate
Pierro, F. D., Carugno, A., Baggi, E., Franco, V., Salati, B., Casale, F., SOARDO, S., Palla, F., Palazzi, C. M., Bertuccioli, A., et al. (2026) · International Microbiology · doi:10.1007/s10123-026-00843-y
“…correlated to a colonic dysbiosis, induced by the antibiotic, characterized by a significant depletion of bifidobacteria and a reduced capacity for acetate production, which in turn is involved in plasma cell metabolism and the production of specific antibodies (Huda et al. 2019, Kim et al. 2016).”
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Probiotic formula intervention in infants leads to colonization and competitive strain displacement independent of IgA bindingPreprint
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“SCFAs are critical immunological mediators that support T-cell regulation, suppress pro-inflammatory cytokine production, drive B-cell differentiation into IgA-and IgG-secreting plasma cells, and increase IgA coating of commensal bacteria 44 .”
The Role of Microbiota in Type 1 Diabetes: Insights into Dysbiosis and Immune Interactions
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Gut commensal bifidobacteria are associated with restrained inflammatory reprogramming in human monocyte-derived dendritic cells
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Total Immunoglobulin G Variation Through the Phenological Cycle of Migrant and Resident Lesser Long‐Nosed Bats (Leptonycteris yerbabuenae) in the Drylands of Mexico and Its Relationship With Bacterial Killing‐Ability of Plasma
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“Despite low tIgG in young individuals and the stability of tIgG in adults, there is a large variability between individuals, which may be a consequence of the genes (Liao et al. 2012), microbiota (Kim et al. 2016; Vujkovic‐Cvijin et al. 2022), and age of the individual (Schneeberger et al. 2014).”
Gut microbiota alterations are associated with uterine immune homeostasis via microbiota-metabolite interactions
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Maternal Perinatal Gut Microbiome Is Shaped by Traditional Farming Lifestyle and Associated With Early Childhood Atopic Disease
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“SCFA have also been shown to support B cell metabolism and differentiation through interactions with T cells or dendritic cells [59, 62, 63].”
Insights Into Gut Microbiota and Metabolic Alterations in Type 1 Diabetes Mellitus
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“SCFAs play a central role in modulating the immune response, particularly through the regulation of B‐cell function and metabolism [5].”
The Immunobiological Path and Fate of the Human Intestinal Allergens and Pathobiont Translocation
Shnawa, I. M. S. (2026) · Journal of Clinical Immunology & Microbiology · doi:10.46889/jcim.2026.7206
Food polysaccharides alleviate inflammatory bowel disease by gut microbiota-metabolism axis
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“…benefits that must be weighed against possible effects on cancer and other host processes (Loonen et al., 2014; Atarashi et al., 2011; Atarashi et al., 2013; Frosali et al., 2015; Bhaskaran et al., 2018; Cao et al., 2012; Yang et al., 2020; Kim et al., 2016; Moor et al., 2017; Hill et al., 2014).”
Short-Chain Fatty Acids at the Crossroads of Microbiota, Immunometabolism, and Inflammation
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Interplay of gut microbiota, immune cells and natural products in reshaping cancer immunotherapy
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The hidden cost of antibiotics: microbial dysbiosis-induced SCFA imbalance and its underlying mechanisms
Ayvazyan, S. R., Darvina, O. V., Turkadze, K. A., Gerasimov, S. G., & Николаевна, К. Н. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1917541 · Cited by 1
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Insights into Microbiota–Vaccine Crosstalk in Humans: Mechanisms, Modulators, and Translational Horizons
Shakri, A. R., Mishra, S. P., Lawless, S., Pani, S., Mishra, P., Page, C. L., Dutta, G., & Sharma, C. (2026) · Vaccines · doi:10.3390/vaccines14090791
“Although it is still debated whether the fetus itself becomes colonized, products and metabolites from the mother’s microbes can reach the fetal compartment and affect immune systems that are still developing [50,51].”
Systemic Humoral Immunity in the Partially Migratory Bat Leptonycteris yerbabuenae is Linked to the Gut Microbiota in a Sex-Specific Manner
Rivera-Ruiz, D. A., Flores‐Martínez, J. J., Rosales, C., Falcón, L. I., Gaona, O., la Cruz, M. T. S.-D., & M., L. G. H. (2026) · Microbial Ecology · doi:10.1007/s00248-026-02881-5
Translating gut microbiome research into therapies for type 1 diabetes
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“Finally, SCFAs have been shown to enhance IgA-mediated mucosal immunity (Kim et al., 2016) and induce B cell differentiation into IL-10-producing regulatory B (Breg) cells (Daïen et al., 2021).”
Secretory IgA and butyrate depletion in Southeast Chinese infants with cow’s milk allergy: pathogenic link and diagnostic biomarker
Chen, X., Xie, X., Shi, X., Gao, X., Ye, H., Zhang, R., & Chen, Y. (2026) · Open Medicine · doi:10.1515/med-2026-1483
“Concurrently, butyrate improves the intestinal barrier through upregulation of tight junction proteins (e.g., Claudin-1, Occludin) and mucin MUC2 expression, which could limits milk protein antigen penetration and alleviates clinical symptoms [13, 14].”
Microbiota-derived metabolites in hematopoietic regulation and disease: mechanisms, context, and therapeutic perspectives
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“In a study, Kim et al. (2016) assessed this discovery further, demonstrating that SCFAs boost antibody responses by modulating gene expression via HDAC inhibition.”
Oral vaccine delivery systems: Gastrointestinal barriers, gut microbiota, and emerging engineering strategies
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Investigation of Oral Toxicity Mechanisms of Low-Molecular-Weight Polycyclic Aromatic Hydrocarbons and Probiotic Interventions Under the Framework of the “Gut–Lung Axis”
Hu, Y.-X., Chen, Z.-X., Luo, D., Tang, Z.-Q., Jiang, S.-Y., Pan, J.-B., Zhao, Y.-Z., Wang, J.-L., & Pan, Y.-X. (2026) · Foods · doi:10.3390/foods15193446
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Gut Microbiota–Mucosal Immune Interactions Underlying Intestinal Homeostasis in Weaned Piglets
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“SCFAs have substantial preclinical mechanistic support, but the molecules differ and direct human vaccine mediation remains unestablished.”
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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.
ORCID: Kim, Myunghoo
Park, Jeongho
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)
DOI: 10.1016/j.chom.2016.07.001
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: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 374 d)
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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Gut Microbial Metabolites Fuel Host Antibody Responses

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