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Volume 13 Issue 5
Sep.  2022
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JIANG Xu, YANG Huaxia, ZHANG Fengchun. The Role of the Gut Microbial Metabolites in Autoimmune Diseases[J]. Medical Journal of Peking Union Medical College Hospital, 2022, 13(5): 747-752. DOI: 10.12290/xhyxzz.2022-0246
Citation: JIANG Xu, YANG Huaxia, ZHANG Fengchun. The Role of the Gut Microbial Metabolites in Autoimmune Diseases[J]. Medical Journal of Peking Union Medical College Hospital, 2022, 13(5): 747-752. DOI: 10.12290/xhyxzz.2022-0246
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The Role of the Gut Microbial Metabolites in Autoimmune Diseases

  • 1.

    State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases, Ministry of Education Key Laboratory, Beijing 100730, China

  • 2.

    Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases, Ministry of Education Key Laboratory, Beijing 100730, China

Funds: 

CAMS Innovation Fund for Medical Sciences 2020-I2M-C & T-B-011

CAMS Innovation Fund for Medical Sciences 2021-I2M-1-016

National Natural Science Foundation of China 82171799

More Information
  • Corresponding author:

    YANG Huaxia, E-mail: yanghuaxia2013@163.com

  • Received Date: May 01, 2022
  • Accepted Date: July 14, 2022
  • Available Online: July 27, 2022
  • Issue Publish Date: September 29, 2022
    Graphical Abstract
    • Abstract
  • The gut microbiota and their metabolites play a critical role in the maintenance of host immune homeostasis. The dysbiosis and gut microbiota-derived metabolites are closely associated with the initiation and development of multiple autoimmune diseases. Among the microbiota metabolites, short-chain fatty acids, tryptophan and its derivatives, and bile acids are the most widely studied. In this review, the metabolic pathway of the microbiota metabolites, their functions in the immune response and the current findings on their correlation with autoimmune diseases are summarized, with the hope of revealing the role of gut microbiota-derived metabolites on the pathogenesis of autoimmune diseases.
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    • References (55)
  • [1]
    Maynard CL, Elson CO, Hatton RD, et al. Reciprocal interactions of the intestinal microbiota and immune system[J]. Nature, 2012, 489: 231-241. DOI: 10.1038/nature11551
    [2]
    Zhang X, Chen BD, Zhao LD, et al. The Gut Microbiota: Emerging Evidence in Autoimmune Diseases[J]. Trends Mol Med, 2020, 26: 862-873. DOI: 10.1016/j.molmed.2020.04.001
    [3]
    Zhang X, Zhang D, Jia H, et al. The oral and gut microbiomes are perturbed in rheumatoid arthritis and partly normalized after treatment[J]. Nat Med, 2015, 21: 895-905. DOI: 10.1038/nm.3914
    [4]
    Alpizar-Rodriguez D, Lesker TR, Gronow A, et al. Prevotella copri in individuals at risk for rheumatoid arthritis[J]. Ann Rheum Dis, 2019, 78: 590-593. DOI: 10.1136/annrheumdis-2018-214514
    [5]
    Azzouz D, Omarbekova A, Heguy A, et al. Lupus nephritis is linked to disease-activity associated expansions and immunity to a gut commensal[J]. Ann Rheum Dis, 2019, 78: 947-956. DOI: 10.1136/annrheumdis-2018-214856
    [6]
    Chen BD, Jia XM, Xu JY, et al. An Autoimmunogenic and Proinflammatory Profile Defined by the Gut Microbiota of Patients With Untreated Systemic Lupus Erythematosus[J]. Arthritis Rheumatol, 2021, 73: 232-243.
    [7]
    Halfvarson J, Brislawn CJ, Lamendella R, et al. Dynamics of the human gut microbiome in inflammatory bowel disease[J]. Nat Microbiol, 2017, 2: 17004. DOI: 10.1038/nmicrobiol.2017.4
    [8]
    Tang R, Wei Y, Li Y, et al. Gut microbial profile is altered in primary biliary cholangitis and partially restored after UDCA therapy[J]. Gut, 2018, 67: 534-541. DOI: 10.1136/gutjnl-2016-313332
    [9]
    Jangi S, Gandhi R, Cox LM, et al. Alterations of the human gut microbiome in multiple sclerosis[J]. Nat Commun, 2016, 7: 12015. DOI: 10.1038/ncomms12015
    [10]
    Wen C, Zheng Z, Shao T, et al. Quantitative metagenomics reveals unique gut microbiome biomarkers in ankylosing spondylitis[J]. Genome Biol, 2017, 18: 142. DOI: 10.1186/s13059-017-1271-6
    [11]
    Zhou C, Zhao H, Xiao XY, et al. Metagenomic profiling of the pro-inflammatory gut microbiota in ankylosing spondylitis[J]. J Autoimmun, 2020, 107: 102360. DOI: 10.1016/j.jaut.2019.102360
    [12]
    Mandl T, Marsal J, Olsson P, et al. Severe intestinal dysbiosis is prevalent in primary Sjögren's syndrome and is associated with systemic disease activity[J]. Arthritis Res Ther, 2017, 19: 237. DOI: 10.1186/s13075-017-1446-2
    [13]
    Ye Z, Zhang N, Wu C, et al. A metagenomic study of the gut microbiome in Behcet's disease[J]. Microbiome, 2018, 6: 135. DOI: 10.1186/s40168-018-0520-6
    [14]
    Schroeder BO. Fight them or feed them: how the intestinal mucus layer manages the gut microbiota[J]. Gastroenterol Rep (Oxf), 2019, 7: 3-12. DOI: 10.1093/gastro/goy052
    [15]
    Nastasi C, Candela M, Bonefeld CM, et al. The effect of short-chain fatty acids on human monocyte-derived dendritic cells[J]. Sci Rep, 2015, 5: 16148. DOI: 10.1038/srep16148
    [16]
    Schulthess J, Pandey S, Capitani M. et al. The Short Chain Fatty Acid Butyrate Imprints an Antimicrobial Program in Macrophages[J]. Immunity, 2019, 50: 432-445. e7. DOI: 10.1016/j.immuni.2018.12.018
    [17]
    Furusawa Y, Obata Y, Fukuda S, et al. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells[J]. Nature, 2013, 504: 446-450. DOI: 10.1038/nature12721
    [18]
    Smith PM, Howitt MR, Panikov N, et al. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis[J]. Science, 2013, 341: 569-573. DOI: 10.1126/science.1241165
    [19]
    Wu W, Sun M, Chen F, et al. Microbiota metabolite short-chain fatty acid acetate promotes intestinal IgA response to microbiota which is mediated by GPR43[J]. Mucosal Immunol, 2017, 10: 946-956. DOI: 10.1038/mi.2016.114
    [20]
    Sun M, Wu W, Chen L, et al. Microbiota-derived short-chain fatty acids promote Th1 cell IL-10 production to maintain intestinal homeostasis[J]. Nat Commun, 2018, 9: 3555. DOI: 10.1038/s41467-018-05901-2
    [21]
    Bachem A, Makhlouf C, Binger KJ, et al. Microbiota-Derived Short-Chain Fatty Acids Promote the Memory Potential of Antigen-Activated CD8(+) T Cells[J]. Immunity, 2019, 51: 285-297. e5. DOI: 10.1016/j.immuni.2019.06.002
    [22]
    Yang W, Yu T, Huang X, et al. Intestinal microbiota-derived short-chain fatty acids regulation of immune cell IL-22 production and gut immunity[J]. Nat Commun, 2020, 11: 4457. DOI: 10.1038/s41467-020-18262-6
    [23]
    Atarashi K, Tanoue T, Oshima K, et al. Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota[J]. Nature, 2013, 500: 232-236. DOI: 10.1038/nature12331
    [24]
    Rosser EC, Piper CJM, Matei DE, et al. Microbiota-Derived Metabolites Suppress Arthritis by Amplifying Aryl-Hydrocarbon Receptor Activation in Regulatory B Cells[J]. Cell Metab, 2020, 31: 837-851. e10. DOI: 10.1016/j.cmet.2020.03.003
    [25]
    Mizuno M, Noto D, Kaga N, et al. The dual role of short fatty acid chains in the pathogenesis of autoimmune disease models[J]. PLoS One, 2017, 12: e0173032. DOI: 10.1371/journal.pone.0173032
    [26]
    Rodriguez-Carrio J, Lopez P, Sanchez B, et al. Intestinal Dysbiosis Is Associated with Altered Short-Chain Fatty Acids and Serum-Free Fatty Acids in Systemic Lupus Erythe-matosus[J]. Front Immunol, 2017, 8: 23.
    [27]
    Zegarra-Ruiz DF, El Beidaq A, Iniguez AJ, et al. A Diet-Sensitive Commensal Lactobacillus Strain Mediates TLR7-Dependent Systemic Autoimmunity[J]. Cell Host Microbe, 2019, 25: 113-127 e6. DOI: 10.1016/j.chom.2018.11.009
    [28]
    Haghikia A, Jorg S, Duscha A, et al. Dietary Fatty Acids Directly Impact Central Nervous System Autoimmunity via the Small Intestine[J]. Immunity, 2015, 43: 817-829. DOI: 10.1016/j.immuni.2015.09.007
    [29]
    Erny D, Hrabe de Angelis AL, Jaitin D, et al. Host microbiota constantly control maturation and function of microglia in the CNS[J]. Nat Neurosci, 2015, 18: 965-977. DOI: 10.1038/nn.4030
    [30]
    Cano-Ortiz A, Laborda-Illanes A, Plaza-Andrades I, et al. Connection between the Gut Microbiome, Systemic Inflamma-tion, Gut Permeability and FOXP3 Expression in Patients with Primary Sjogren's Syndrome[J]. Int J Mol Sci, 2020, 21: 8733. DOI: 10.3390/ijms21228733
    [31]
    Chen X, Su W, Wan T, et al. Sodium butyrate regulates Th17/Treg cell balance to ameliorate uveitis via the Nrf2/HO-1 pathway[J]. Biochem Pharmacol, 2017, 142: 111-119. DOI: 10.1016/j.bcp.2017.06.136
    [32]
    Lloyd-Price J, Arze C, Ananthakrishnan AN, et al. Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases[J]. Nature, 2019, 569: 655-662. DOI: 10.1038/s41586-019-1237-9
    [33]
    Biagioli M, Carino A, Cipriani S, et al. The Bile Acid Receptor GPBAR1 Regulates the M1/M2 Phenotype of Intes-tinal Macrophages and Activation of GPBAR1 Rescues Mice from Murine Colitis[J]. J Immunol, 2017, 199: 718-733. DOI: 10.4049/jimmunol.1700183
    [34]
    Krautkramer KA, Fan J, Backhed F. Gut microbial metabolites as multi-kingdom intermediates[J]. Nat Rev Microbiol, 2021, 19: 77-94. DOI: 10.1038/s41579-020-0438-4
    [35]
    Singh NP, Singh UP, Rouse M, et al. Dietary Indoles Suppress Delayed-Type Hypersensitivity by Inducing a Switch from Proinflammatory Th17 Cells to Anti-Inflammatory Regulatory T Cells through Regulation of MicroRNA[J]. J Immunol, 2016, 196: 1108-1122. DOI: 10.4049/jimmunol.1501727
    [36]
    Cervantes-Barragan L, Chai JN, Tianero MD, et al. Lactobacillus reuteri induces gut intraepithelial CD4(+)CD8alphaalpha(+) T cells[J]. Science, 2017, 357: 806-810. DOI: 10.1126/science.aah5825
    [37]
    Pongratz G, Lowin T, Sewerin P, et al. Tryptophan metabolism in rheumatoid arthritis is associated with rheumatoid factor and predicts joint pathology evaluated by the Rheumatoid Arthritis MRI Score (RAMRIS)[J]. Clin Exp Rheumatol, 2019, 37: 450-457.
    [38]
    Hasan H, Ismail H, El-Orfali Y, et al. Therapeutic benefits of Indole-3-Carbinol in adjuvant-induced arthritis and its protective effect against methotrexate induced-hepatic toxicity[J]. BMC Complement Altern Med, 2018, 18: 337. DOI: 10.1186/s12906-018-2408-1
    [39]
    Langan D, Perkins DJ, Vogel SN, et al. Microbiota-Derived Metabolites, Indole-3-aldehyde and Indole-3-acetic Acid, Differentially Modulate Innate Cytokines and Stromal Remodeling Processes Associated with Autoimmune Arthritis[J]. Int J Mol Sci, 2021, 22.
    [40]
    Rothhammer V, Mascanfroni ID, Bunse L, et al. Type I interferons and microbial metabolites of tryptophan modulate astrocyte activity and central nervous system inflammation via the aryl hydrocarbon receptor[J]. Nat Med, 2016, 22: 586-597. DOI: 10.1038/nm.4106
    [41]
    Lamas B, Richard ML, Leducq V, et al. CARD9 impacts colitis by altering gut microbiota metabolism of tryptophan into aryl hydrocarbon receptor ligands[J]. Nat Med, 2016, 22: 598-605. DOI: 10.1038/nm.4102
    [42]
    Stockinger B, Shah K, Wincent E. AHR in the intestinal microenvironment: safeguarding barrier function[J]. Nat Rev Gastroenterol Hepatol, 2021, 18: 559-570. DOI: 10.1038/s41575-021-00430-8
    [43]
    Funabashi M, Grove TL, Wang M, et al. A metabolic pathway for bile acid dehydroxylation by the gut microbiome[J]. Nature, 2020, 582: 566-570. DOI: 10.1038/s41586-020-2396-4
    [44]
    Jia W, Xie G, Jia W. Bile acid-microbiota crosstalk in gastrointestinal inflammation and carcinogenesis[J]. Nat Rev Gastroenterol Hepatol, 2018, 15: 111-128. DOI: 10.1038/nrgastro.2017.119
    [45]
    Fiorucci S, Biagioli M, Zampella A, et al. Bile Acids Activated Receptors Regulate Innate Immunity[J]. Front Immunol, 2018, 9: 1853. DOI: 10.3389/fimmu.2018.01853
    [46]
    Hang S, Paik D, Yao L, et al. Bile acid metabolites control TH17 and Treg cell differentiation[J]. Nature, 2019, 576: 143-148. DOI: 10.1038/s41586-019-1785-z
    [47]
    Song X, Sun X, Oh SF, et al. Microbial bile acid metabolites modulate gut RORgamma(+) regulatory T cell homeostasis[J]. Nature, 2020, 577: 410-415. DOI: 10.1038/s41586-019-1865-0
    [48]
    Ma C, Han M, Heinrich B, et al. Gut microbiome-mediated bile acid metabolism regulates liver cancer via NKT cells[J]. Science, 2018, 360: eaan5931. DOI: 10.1126/science.aan5931
    [49]
    Chen W, Wei Y, Xiong A, et al. Comprehensive Analysis of Serum and Fecal Bile Acid Profiles and Interaction with Gut Microbiota in Primary Biliary Cholangitis[J]. Clin Rev Allergy Immunol, 2020, 58: 25-38. DOI: 10.1007/s12016-019-08731-2
    [50]
    Li B, Zhang J, Chen Y, et al. Alterations in microbiota and their metabolites are associated with beneficial effects of bile acid sequestrant on icteric primary biliary Cholangitis[J]. Gut Microbes, 2021, 13: 1946366. DOI: 10.1080/19490976.2021.1946366
    [51]
    Bartikoski BJ, De Oliveira MS, Do Espirito Santo RC, et al. A Review of Metabolomic Profiling in Rheumatoid Arthritis: Bringing New Insights in Disease Pathogenesis, Treatment and Comorbidities[J]. Metabolites, 2022, 12: 394. DOI: 10.3390/metabo12050394
    [52]
    Li ZY, Zhou JJ, Luo CL, et al. Activation of TGR5 alleviates inflammation in rheumatoid arthritis peripheral blood mononuclear cells and in mice with collagen Ⅱinduced arthritis[J]. Mol Med Rep, 2019, 20: 4540-4550.
    [53]
    He J, Chan T, Hong X, et al. Microbiome and Metabolome Analyses Reveal the Disruption of Lipid Metabolism in Systemic Lupus Erythematosus[J]. Front Immunol, 2020, 11: 1703. DOI: 10.3389/fimmu.2020.01703
    [54]
    Lian F, Wang Y, Chen J, et al. Activation of farnesoid X receptor attenuates liver injury in systemic lupus erythema-tosus[J]. Rheumatol Int, 2012, 32: 1705-1710. DOI: 10.1007/s00296-011-1874-2
    [55]
    Gadaleta RM, Garcia-Irigoyen O, Cariello M, et al. Fibroblast Growth Factor 19 modulates intestinal microbiota and inflammation in presence of Farnesoid X Receptor[J]. EBioMedicine, 2020, 54: 102719. DOI: 10.1016/j.ebiom.2020.102719
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