Skip to main content
SpringerLink
Log in

Recent advances in systemic lupus erythematosus and microbiota: from bench to bedside

  • Review
  • Published:
Frontiers of Medicine Aims and scope Submit manuscript

Abstract

Systemic lupus erythematosus (SLE) is a complicated autoimmune disease affecting multiple systems and organs. It is highly heterogeneous, and it preferentially affects women at childbearing age, causing worldwide social burden. The pathogenesis of SLE mostly involves genetic predisposition, epigenetic dysregulation, overactivation of the immune system, and environment factors. Human microbiome, which is mostly composed of microbiota colonized in the gut, skin, and oral cavity, provides a natural microbiome barrier against environmental risks. The past decade of research has demonstrated a strong association between microbiota and metabolic diseases or gastrointestinal diseases. However, the role of microbiota in autoimmunity remains largely unknown until recently, when the technological and methodological progress facilitates further microbiota research in SLE. In this review, the latest research about the role and mechanisms of microbiota in SLE and the advances in the development of diagnostic and therapeutic strategies based on microbiota for SLE were summarized.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Tsokos GC. Systemic lupus erythematosus. N Engl J Med 2011; 365(22): 2110–2121

    Article  CAS  PubMed  Google Scholar 

  2. Dema B, Charles N. Autoantibodies in SLE: specificities, isotypes and receptors. Antibodies (Basel) 2016; 5(1): 2

    Article  Google Scholar 

  3. Tsokos GC, Lo MS, Costa Reis P, Sullivan KE. New insights into the immunopathogenesis of systemic lupus erythematosus. Nat Rev Rheumatol 2016; 12(12): 716–730

    Article  CAS  PubMed  Google Scholar 

  4. Espéli M, Smith KG, Clatworthy MR. FcγRIIB and autoimmunity. Immunol Rev 2016; 269(1): 194–211

    Article  PubMed  Google Scholar 

  5. Honda K, Littman DR. The microbiota in adaptive immune homeostasis and disease. Nature 2016; 535(7610): 75–84

    Article  CAS  PubMed  Google Scholar 

  6. Fu R, Xia Y, Li M, Mao R, Guo C, Zhou M, Tan H, Liu M, Wang S, Yang N, Zhao J. Pim-1 as a therapeutic target in human lupus nephritis. Arthritis Rheumatol 2019; 71(8): 1308–1318

    Article  CAS  PubMed  Google Scholar 

  7. Singh S, Li SSL. Epigenetic effects of environmental chemicals bisphenol A and phthalates. Int J Mol Sci 2012; 13(8): 10143–10153

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Wu SE, Hashimoto-Hill S, Woo V, Eshleman EM, Whitt J, Engleman L, Karns R, Denson LA, Haslam DB, Alenghat T. Microbiota-derived metabolite promotes HDAC3 activity in the gut. Nature 2020; 586(7827): 108–112

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Sánchez B, Hevia A, González S, Margolles A. Interaction of intestinal microorganisms with the human host in the framework of autoimmune diseases. Front Immunol 2015; 6: 594

    Article  PubMed  PubMed Central  Google Scholar 

  10. Gensollen T, Iyer SS, Kasper DL, Blumberg RS. How colonization by microbiota in early life shapes the immune system. Science 2016; 352(6285): 539–544

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Bach JF. The hygiene hypothesis in autoimmunity: the role of pathogens and commensals. Nat Rev Immunol 2018; 18(2): 105–120

    Article  CAS  PubMed  Google Scholar 

  12. Huang C, Yi X, Long H, Zhang G, Wu H, Zhao M, Lu Q. Disordered cutaneous microbiota in systemic lupus erythematosus. J Autoimmun 2020; 108: 102391

    Article  PubMed  Google Scholar 

  13. Luo S, Long H, Lu Q. Recent advances in understanding pathogenesis and therapeutic strategies of systemic lupus erythematosus. Int Immunopharmacol 2020; 89 (Pt A): 107028

    Article  CAS  PubMed  Google Scholar 

  14. Biliouris K, Nestorov I, Naik H, Dai D, Xiao G, Wang Q, Pellerin A, Rabah D, Lesko LJ, Trame MN. A pre-clinical quantitative model predicts the pharmacokinetics/pharmacodynamics of an anti-BDCA2 monoclonal antibody in humans. J Pharmacokinet Pharmacodyn 2018; 45(6): 817–827

    Article  CAS  PubMed  Google Scholar 

  15. Markham A. Baricitinib: first global approval. Drugs 2017; 77(6): 697–704

    Article  CAS  PubMed  Google Scholar 

  16. Mathian A, Pha M, Haroche J, Cohen-Aubart F, Hié M, Pineton de Chambrun M, Boutin THD, Miyara M, Gorochov G, Yssel H, Cherin P, Devilliers H, Amoura Z. Withdrawal of low-dose prednisone in SLE patients with a clinically quiescent disease for more than 1 year: a randomised clinical trial. Ann Rheum Dis 2020; 79(3): 339–346

    Article  CAS  PubMed  Google Scholar 

  17. Rahbar Saadat Y, Hejazian M, Bastami M, Hosseinian Khatibi SM, Ardalan M, Zununi Vahed S. The role of microbiota in the pathogenesis of lupus: dose it impact lupus nephritis? Pharmacol Res 2019; 139: 191–198

    Article  CAS  PubMed  Google Scholar 

  18. Human Microbiome Project Consortium. Structure, function and diversity of the healthy human microbiome. Nature 2012; 486(7402): 207–214

    Article  Google Scholar 

  19. Andoh A. Physiological role of gut microbiota for maintaining human health. Digestion 2016; 93(3): 176–181

    Article  CAS  PubMed  Google Scholar 

  20. Choi SC, Brown J, Gong M, Ge Y, Zadeh M, Li W, Croker BP, Michailidis G, Garrett TJ, Mohamadzadeh M, Morel L. Gut microbiota dysbiosis and altered tryptophan catabolism contribute to autoimmunity in lupus-susceptible mice. Sci Transl Med 2020; 12(551): eaax2220

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Zhang L, Qing P, Yang H, Wu Y, Liu Y, Luo Y. Gut microbiome and metabolites in systemic lupus erythematosus: link, mechanisms and intervention. Front Immunol 2021; 12: 686501

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Neish AS. Microbes in gastrointestinal health and disease. Gastroenterology 2009; 136(1): 65–80

    Article  PubMed  Google Scholar 

  23. Heintz-Buschart A, Wilmes P. Human gut microbiome: function matters. Trends Microbiol 2018; 26(7): 563–574

    Article  CAS  PubMed  Google Scholar 

  24. Apperloo-Renkema HZ, Bootsma H, Mulder BI, Kallenberg CG, van der Waaij D. Host-microflora interaction in systemic lupus erythematosus (SLE): circulating antibodies to the indigenous bacteria of the intestinal tract. Epidemiol Infect 1995; 114(1): 133–141

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Hevia A, Milani C, López P, Cuervo A, Arboleya S, Duranti S, Turroni F, González S, Suárez A, Gueimonde M, Ventura M, Sánchez B, Margolles A. Intestinal dysbiosis associated with systemic lupus erythematosus. MBio 2014; 5(5): e01548–14

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Boerner BP, Sarvetnick NE. Type 1 diabetes: role of intestinal microbiome in humans and mice. Ann N Y Acad Sci 2011; 1243(1): 103–118

    Article  CAS  PubMed  Google Scholar 

  27. Brown CT, Davis-Richardson AG, Giongo A, Gano KA, Crabb DB, Mukherjee N, Casella G, Drew JC, Ilonen J, Knip M, Hyöty H, Veijola R, Simell T, Simell O, Neu J, Wasserfall CH, Schatz D, Atkinson MA, Triplett EW. Gut microbiome metagenomics analysis suggests a functional model for the development of autoimmunity for type 1 diabetes. PLoS One 2011; 6(10): e25792

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Kasselman LJ, Vernice NA, DeLeon J, Reiss AB. The gut microbiome and elevated cardiovascular risk in obesity and autoimmunity. Atherosclerosis 2018; 271: 203–213

    Article  CAS  PubMed  Google Scholar 

  29. López P, de Paz B, Rodríguez-Carrio J, Hevia A, Sánchez B, Margolles A, Suárez A. Th17 responses and natural IgM antibodies are related to gut microbiota composition in systemic lupus erythematosus patients. Sci Rep 2016; 6(1): 24072

    Article  PubMed  PubMed Central  Google Scholar 

  30. Wei F, Xu H, Yan C, Rong C, Liu B, Zhou H. Changes of intestinal flora in patients with systemic lupus erythematosus in northeast China. PLoS One 2019; 14(3): e0213063

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. He Z, Shao T, Li H, Xie Z, Wen C. Alterations of the gut microbiome in Chinese patients with systemic lupus erythematosus. Gut Pathog 2016; 8(1): 64

    Article  PubMed  PubMed Central  Google Scholar 

  32. Gerges MA, Esmaeel NE, Makram WK, Sharaf DM, Gebriel MG. Altered profile of fecal microbiota in newly diagnosed systemic lupus erythematosus Egyptian patients. Int J Microbiol 2021; 2021: 9934533

    Article  PubMed  PubMed Central  Google Scholar 

  33. Zhu WF. Alteration of gut microbiome in patients with systemic lupus erythematosus. Doctoral dissertation. Hangzhou: Zhejiang University, 2018 (in Chinese)

    Google Scholar 

  34. Luo XM, Edwards MR, Mu Q, Yu Y, Vieson MD, Reilly CM, Ahmed SA, Bankole AA. Gut microbiota in human systemic lupus erythematosus and a mouse model of lupus. Appl Environ Microbiol 2018; 84(4): e02288–17

    Article  PubMed  PubMed Central  Google Scholar 

  35. Azzouz D, Omarbekova A, Heguy A, Schwudke D, Gisch N, Rovin BH, Caricchio R, Buyon JP, Alekseyenko AV, Silverman GJ. Lupus nephritis is linked to disease-activity associated expansions and immunity to a gut commensal. Ann Rheum Dis 2019; 78(7): 947–956

    Article  CAS  PubMed  Google Scholar 

  36. Li Y, Wang HF, Li X, Li HX, Zhang Q, Zhou HW, He Y, Li P, Fu C, Zhang XH, Qiu YR, Li JL. Disordered intestinal microbes are associated with the activity of systemic lupus erythematosus. Clin Sci (Lond) 2019; 133(7): 821–838

    Article  CAS  Google Scholar 

  37. Lu Q, Wu A, Tesmer L, Ray D, Yousif N, Richardson B. Demethylation of CD40LG on the inactive X in T cells from women with lupus. J Immunol 2007; 179(9): 6352–6358

    Article  CAS  PubMed  Google Scholar 

  38. Mu Q, Cabana-Puig X, Mao J, Swartwout B, Abdelhamid L, Cecere TE, Wang H, Reilly CM, Luo XM. Pregnancy and lactation interfere with the response of autoimmunity to modulation of gut microbiota. Microbiome 2019; 7(1): 105

    Article  PubMed  PubMed Central  Google Scholar 

  39. Mu Q, Zhang H, Luo XM. SLE: another autoimmune disorder influenced by microbes and diet? Front Immunol 2015; 6: 608

    Article  PubMed  PubMed Central  Google Scholar 

  40. Guo M, Wang H, Xu S, Zhuang Y, An J, Su C, Xia Y, Chen J, Xu ZZ, Liu Q, Wang J, Dan Z, Chen K, Luan X, Liu Z, Liu K, Zhang F, Xia Y, Liu X. Alteration in gut microbiota is associated with dysregulation of cytokines and glucocorticoid therapy in systemic lupus erythematosus. Gut Microbes 2020; 11(6): 1758–1773

    Article  PubMed  PubMed Central  Google Scholar 

  41. Wen M, Liu T, Zhao M, Dang X, Feng S, Ding X, Xu Z, Huang X, Lin Q, Xiang W, Li X, He X, He Q. Correlation analysis between gut microbiota and metabolites in children with systemic lupus erythematosus. J Immunol Res 2021; 2021: 5579608

    Article  PubMed  PubMed Central  Google Scholar 

  42. Sonnenburg JL, Bäckhed F. Diet-microbiota interactions as moderators of human metabolism. Nature 2016; 535(7610): 56–64

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Rojo D, Hevia A, Bargiela R, López P, Cuervo A, González S, Suárez A, Sánchez B, Martínez-Martínez M, Milani C, Ventura M, Barbas C, Moya A, Suárez A, Margolles A, Ferrer M. Ranking the impact of human health disorders on gut metabolism: systemic lupus erythematosus and obesity as study cases. Sci Rep 2015; 5(1): 8310

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Rodríguez-Carrio J, López P, Sánchez B, González S, Gueimonde M, Margolles A, de Los Reyes-Gavilán CG, Suárez A. Intestinal dysbiosis is associated with altered short-chain fatty acids and serum-free fatty acids in systemic lupus erythematosus. Front Immunol 2017; 8: 23

    Article  PubMed  PubMed Central  Google Scholar 

  45. González S, Gutie Rrez-Díaz I, Lo Pez P, Suárez A, Fernández-Navarro T, Sánchez B, Margolles A. Microbiota and oxidant-antioxidant balance in systemic lupus erythematosus. Nutr Hosp 2017; 34(4): 934–941

    PubMed  Google Scholar 

  46. Manfredo Vieira S, Hiltensperger M, Kumar V, Zegarra-Ruiz D, Dehner C, Khan N, Costa FRC, Tiniakou E, Greiling T, Ruff W, Barbieri A, Kriegel C, Mehta SS, Knight JR, Jain D, Goodman AL, Kriegel MA. Translocation of a gut pathobiont drives autoimmunity in mice and humans. Science 2018; 359(6380): 1156–1161

    Article  CAS  PubMed  Google Scholar 

  47. Bellocchi C, Fernández-Ochoa Á, Montanelli G, Vigone B, Santaniello A, Quirantes-Piné R, Borrás-Linares I, Gerosa M, Artusi C, Gualtierotti R, Segura-Carrettero A, Alarcón-Riquelme ME, Beretta L. Identification of a shared microbiomic and metabolomic profile in systemic autoimmune diseases. J Clin Med 2019; 8(9): 1291

    Article  CAS  PubMed Central  Google Scholar 

  48. Tomofuji Y, Maeda Y, Oguro-Igashira E, Kishikawa T, Yamamoto K, Sonehara K, Motooka D, Matsumoto Y, Matsuoka H, Yoshimura M, Yagita M, Nii T, Ohshima S, Nakamura S, Inohara H, Takeda K, Kumanogoh A, Okada Y. Metagenome-wide association study revealed disease-specific landscape of the gut microbiome of systemic lupus erythematosus in Japanese. Ann Rheum Dis 2021; 80(12): 1575–1583

    Article  CAS  PubMed  Google Scholar 

  49. Chen BD, Jia XM, Xu JY, Zhao LD, Ji JY, Wu BX, Ma Y, Li H, Zuo XX, Pan WY, Wang XH, Ye S, Tsokos GC, Wang J, Zhang X. An autoimmunogenic and proinflammatory profile defined by the gut microbiota of patients with untreated systemic lupus erythematosus. Arthritis Rheumatol 2021; 73(2): 232–243

    Article  CAS  PubMed  Google Scholar 

  50. de la Visitación N, Robles-Vera I, Toral M, Duarte J. Protective effects of probiotic consumption in cardiovascular disease in systemic lupus erythematosus. Nutrients 2019; 11(11): 2676

    Article  PubMed Central  Google Scholar 

  51. Mu Q, Zhang H, Liao X, Lin K, Liu H, Edwards MR, Ahmed SA, Yuan R, Li L, Cecere TE, Branson DB, Kirby JL, Goswami P, Leeth CM, Read KA, Oestreich KJ, Vieson MD, Reilly CM, Luo XM. Control of lupus nephritis by changes of gut microbiota. Microbiome 2017; 5(1): 73

    Article  PubMed  PubMed Central  Google Scholar 

  52. de la Visitación N, Robles-Vera I, Toral M, Gómez-Guzmán M, Sánchez M, Moleón J, González-Correa C, Martín-Morales N, O’Valle F, Jiménez R, Romero M, Duarte J. Gut microbiota contributes to the development of hypertension in a genetic mouse model of systemic lupus erythematosus. Br J Pharmacol 2021; 178(18): 3708–3729

    Article  PubMed  Google Scholar 

  53. Egert M, Simmering R, Riedel CU. The association of the skin microbiota with health, immunity, and disease. Clin Pharmacol Ther 2017; 102(1): 62–69

    Article  CAS  PubMed  Google Scholar 

  54. Flowers L, Grice EA. The skin microbiota: balancing risk and reward. Cell Host Microbe 2020; 28(2): 190–200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Ribero S, Sciascia S, Borradori L, Lipsker D. The cutaneous spectrum of lupus erythematosus. Clin Rev Allergy Immunol 2017; 53(3): 291–305

    Article  PubMed  Google Scholar 

  56. Zhou HY, Cao NW, Guo B, Chen WJ, Tao JH, Chu XJ, Meng X, Zhang TX, Li BZ. Systemic lupus erythematosus patients have a distinct structural and functional skin microbiota compared with controls. Lupus 2021; 30(10): 1553–1564

    Article  CAS  PubMed  Google Scholar 

  57. van der Meulen TA, Harmsen HJM, Vila AV, Kurilshikov A, Liefers SC, Zhernakova A, Fu J, Wijmenga C, Weersma RK, de Leeuw K, Bootsma H, Spijkervet FKL, Vissink A, Kroese FGM. Shared gut, but distinct oral microbiota composition in primary Sjögren’s syndrome and systemic lupus erythematosus. J Autoimmun 2019; 97: 77–87

    Article  PubMed  Google Scholar 

  58. Clancy RM, Marion MC, Ainsworth HC, Blaser MJ, Chang M, Howard TD, Izmirly PM, Lacher C, Masson M, Robins K, Buyon JP, Langefeld CD. Salivary dysbiosis and the clinical spectrum in anti-Ro positive mothers of children with neonatal lupus. J Autoimmun 2020; 107: 102354

    Article  CAS  PubMed  Google Scholar 

  59. Corrêa JD, Calderaro DC, Ferreira GA, Mendonça SM, Fernandes GR, Xiao E, Teixeira AL, Leys EJ, Graves DT, Silva TA. Subgingival microbiota dysbiosis in systemic lupus erythematosus: association with periodontal status. Microbiome 2017; 5(1): 34

    Article  PubMed  PubMed Central  Google Scholar 

  60. Rutter-Locher Z, Smith TO, Giles I, Sofat N. Association between systemic lupus erythematosus and periodontitis: a systematic review and meta-analysis. Front Immunol 2017; 8: 1295

    Article  PubMed  PubMed Central  Google Scholar 

  61. Pessoa L, Aleti G, Choudhury S, Nguyen D, Yaskell T, Zhang Y, Li W, Nelson KE, Neto LLS, Sant’Ana ACP, Freire M. Host-microbial interactions in systemic lupus erythematosus and periodontitis. Front Immunol 2019; 10: 2602

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Marques CP, Victor EC, Franco MM, Fernandes JM, Maor Y, de Andrade MS, Rodrigues VP, Benatti BB. Salivary levels of inflammatory cytokines and their association to periodontal disease in systemic lupus erythematosus patients. A case-control study. Cytokine 2016; 85: 165–170

    Article  CAS  PubMed  Google Scholar 

  63. Fabbri C, Fuller R, Bonfá E, Guedes LK, D’Alleva PS, Borba EF. Periodontitis treatment improves systemic lupus erythematosus response to immunosuppressive therapy. Clin Rheumatol 2014; 33(4): 505–509

    Article  PubMed  Google Scholar 

  64. Liu F, Ren T, Li X, Zhai Q, Xu X, Zhang N, Jiang P, Niu Y, Lv L, Shi G, Feng N. Distinct microbiomes of gut and saliva in patients with systemic lupus erythematous and clinical associations. Front Immunol 2021; 12: 626217

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Li BZ, Zhou HY, Guo B, Chen WJ, Tao JH, Cao NW, Chu XJ, Meng X. Dysbiosis of oral microbiota is associated with systemic lupus erythematosus. Arch Oral Biol 2020; 113: 104708

    Article  CAS  PubMed  Google Scholar 

  66. Potgieter M, Bester J, Kell DB, Pretorius E. The dormant blood microbiome in chronic, inflammatory diseases. FEMS Microbiol Rev 2015; 39(4): 567–591

    Article  PubMed  PubMed Central  Google Scholar 

  67. Kiyohara H, Sujino T, Teratani T, Miyamoto K, Arai MM, Nomura E, Harada Y, Aoki R, Koda Y, Mikami Y, Mizuno S, Naganuma M, Hisamatsu T, Kanai T. Toll-like receptor 7 agonist-induced dermatitis causes severe dextran sulfate sodium colitis by altering the gut microbiome and immune cells. Cell Mol Gastroenterol Hepatol 2019; 7(1): 135–156

    Article  PubMed  Google Scholar 

  68. Shi L, Zhang Z, Yu AM, Wang W, Wei Z, Akhter E, Maurer K, Costa Reis P, Song L, Petri M, Sullivan KE. The SLE transcriptome exhibits evidence of chronic endotoxin exposure and has widespread dysregulation of non-coding and coding RNAs. PLoS One 2014; 9(5): e93846

    Article  PubMed  PubMed Central  Google Scholar 

  69. Fotis L, Shaikh N, Baszis KW, Samson CM, Lev-Tzion R, French AR, Tarr PI. Serologic evidence of gut-driven systemic inflammation in juvenile idiopathic arthritis. J Rheumatol 2017; 44(11): 1624–1631

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Greiling TM, Dehner C, Chen X, Hughes K, Iñiguez AJ, Boccitto M, Ruiz DZ, Renfroe SC, Vieira SM, Ruff WE, Sim S, Kriegel C, Glanternik J, Chen X, Girardi M, Degnan P, Costenbader KH, Goodman AL, Wolin SL, Kriegel MA. Commensal orthologs of the human autoantigen Ro60 as triggers of autoimmunity in lupus. Sci Transl Med 2018; 10(434): eaan2306

    Article  PubMed  PubMed Central  Google Scholar 

  71. Corrêa JD, Calderaro DC, Ferreira GA, Mendonça SM, Fernandes GR, Xiao E, Teixeira AL, Leys EJ, Graves DT, Silva TA. Subgingival microbiota dysbiosis in systemic lupus erythematosus: association with periodontal status. Microbiome 2017; 5(1): 34

    Article  PubMed  PubMed Central  Google Scholar 

  72. Zegarra-Ruiz DF, El Beidaq A, Iñiguez AJ, Lubrano Di Ricco M, Manfredo Vieira S, Ruff WE, Mubiru D, Fine RL, Sterpka J, Greiling TM, Dehner C, Kriegel MA. A diet-sensitive commensal lactobacillus strain mediates TLR7-dependent systemic autoimmunity. Cell Host Microbe 2019; 25(1): 113–127.e6

    Article  CAS  PubMed  Google Scholar 

  73. Ruff WE, Greiling TM, Kriegel MA. Host-microbiota interactions in immune-mediated diseases. Nat Rev Microbiol 2020; 18(9): 521–538

    Article  CAS  PubMed  Google Scholar 

  74. Belkaid Y, Hand TW. Role of the microbiota in immunity and inflammation. Cell 2014; 157(1): 121–141

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Zhang S, Wang J, Chen J, Zhang M, Zhang Y, Hu F, Lv Z, Gao C, Li Y, Li X. The level of peripheral regulatory T cells is linked to changes in gut commensal microflora in patients with systemic lupus erythematosus. Ann Rheum Dis 2021; 80(11): e177

    Article  PubMed  Google Scholar 

  76. Naik S, Bouladoux N, Linehan JL, Han SJ, Harrison OJ, Wilhelm C, Conlan S, Himmelfarb S, Byrd AL, Deming C, Quinones M, Brenchley JM, Kong HH, Tussiwand R, Murphy KM, Merad M, Segre JA, Belkaid Y. Commensal-dendritic-cell interaction specifies a unique protective skin immune signature. Nature 2015; 520(7545): 104–108

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Coit P, Sawalha AH. The human microbiome in rheumatic autoimmune diseases: a comprehensive review. Clin Immunol 2016; 170: 70–79

    Article  CAS  PubMed  Google Scholar 

  78. Katz-Agranov N, Zandman-Goddard G. The microbiome and systemic lupus erythematosus. Immunol Res 2017; 65(2): 432–437

    Article  CAS  PubMed  Google Scholar 

  79. Toral M, Gómez-Guzmán M, Jiménez R, Romero M, Sánchez M, Utrilla MP, Garrido-Mesa N, Rodríguez-Cabezas ME, Olivares M, Gálvez J, Duarte J. The probiotic Lactobacillus coryniformis CECT5711 reduces the vascular pro-oxidant and pro-inflammatory status in obese mice. Clin Sci (Lond) 2014; 127(1): 33–45

    Article  Google Scholar 

  80. Zhao Y, Zhang B, Liu C, Ren G. Method for accurate diagnose of lupus erythematosus skin lesions based on microbial rDNA sequencing. Saudi J Biol Sci 2020; 27(8): 2111–2115

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. He Z, Kong X, Shao T, Zhang Y, Wen C. Alterations of the gut microbiota associated with promoting efficacy of prednisone by bromofuranone in MRL/lpr mice. Front Microbiol 2019; 10: 978

    Article  PubMed  PubMed Central  Google Scholar 

  82. Toral M, Robles-Vera I, Romero M, de la Visitación N, Sánchez M, O’Valle F, Rodriguez-Nogales A, Gálvez J, Duarte J, Jiménez R. Lactobacillus fermentum CECT5716: a novel alternative for the prevention of vascular disorders in a mouse model of systemic lupus erythematosus. FASEB J 2019; 33(9): 10005–10018

    Article  CAS  PubMed  Google Scholar 

  83. de la Visitación N, Robles-Vera I, Moleón-Moya J, Sánchez M, Jiménez R, Gómez-Guzmán M, González-Correa C, Olivares M, Toral M, Romero M, Duarte J. Probiotics prevent hypertension in a murine model of systemic lupus erythematosus induced by Tolllike receptor 7 activation. Nutrients 2021; 13(8): 2669

    Article  PubMed  PubMed Central  Google Scholar 

  84. Hsu TC, Huang CY, Liu CH, Hsu KC, Chen YH, Tzang BS. Lactobacillus paracasei GMNL-32, Lactobacillus reuteri GMNL-89 and L. reuteri GMNL-263 ameliorate hepatic injuries in lupus-prone mice. Br J Nutr 2017; 117(8): 1066–1074

    Article  CAS  PubMed  Google Scholar 

  85. Yeh YL, Lu MC, Tsai BC, Tzang BS, Cheng SM, Zhang X, Yang LY, Mahalakshmi B, Kuo WW, Xiang P, Huang CY. Heat-killed Lactobacillus reuteri GMNL-263 inhibits systemic lupus erythematosus-induced cardiomyopathy in NZB/W F1 mice. Probiotics Antimicrob Proteins 2021; 13(1): 51–59

    Article  CAS  PubMed  Google Scholar 

  86. Tzang BS, Liu CH, Hsu KC, Chen YH, Huang CY, Hsu TC. Effects of oral Lactobacillus administration on antioxidant activities and CD4+CD25+forkhead box P3 (FoxP3)+ T cells in NZB/W F1 mice. Br J Nutr 2017; 118(5): 333–342

    Article  CAS  PubMed  Google Scholar 

  87. Esmaeili SA, Mahmoudi M, Rezaieyazdi Z, Sahebari M, Tabasi N, Sahebkar A, Rastin M. Generation of tolerogenic dendritic cells using Lactobacillus rhamnosus and Lactobacillus delbrueckii as tolerogenic probiotics. J Cell Biochem 2018; 119(9): 7865–7872

    Article  CAS  PubMed  Google Scholar 

  88. Mardani F, Mahmoudi M, Esmaeili SA, Khorasani S, Tabasi N, Rastin M. In vivo study: Th1-Th17 reduction in pristane-induced systemic lupus erythematosus mice after treatment with tolerogenic Lactobacillus probiotics. J Cell Physiol 2019; 234(1): 642–649

    Article  CAS  Google Scholar 

  89. Khorasani S, Mahmoudi M, Kalantari MR, Lavi Arab F, Esmaeili SA, Mardani F, Tabasi N, Rastin M. Amelioration of regulatory T cells by Lactobacillus delbrueckii and Lactobacillus rhamnosus in pristane-induced lupus mice model. J Cell Physiol 2019; 234(6): 9778–9786

    Article  CAS  PubMed  Google Scholar 

  90. Cuervo A, Hevia A, López P, Suárez A, Sánchez B, Margolles A, González S. Association of polyphenols from oranges and apples with specific intestinal microorganisms in systemic lupus erythematosus patients. Nutrients 2015; 7(2): 1301–1317

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Johnson BM, Gaudreau MC, Al-Gadban MM, Gudi R, Vasu C. Impact of dietary deviation on disease progression and gut microbiome composition in lupus-prone SNF1 mice. Clin Exp Immunol 2015; 181(2): 323–337

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Wolter M, Grant ET, Boudaud M, Steimle A, Pereira GV, Martens EC, Desai MS. Leveraging diet to engineer the gut microbiome. Nat Rev Gastroenterol Hepatol 2021; 18(12): 885–902

    Article  CAS  PubMed  Google Scholar 

  93. Schäfer AL, Eichhorst A, Hentze C, Kraemer AN, Amend A, Sprenger DTL, Fluhr C, Finzel S, Daniel C, Salzer U, Rizzi M, Voll RE, Chevalier N. Low dietary fiber intake links development of obesity and lupus pathogenesis. Front Immunol 2021; 12: 696810

    Article  PubMed  PubMed Central  Google Scholar 

  94. Mocanu V, Zhang Z, Deehan EC, Kao DH, Hotte N, Karmali S, Birch DW, Samarasinghe KK, Walter J, Madsen KL. Fecal microbial transplantation and fiber supplementation in patients with severe obesity and metabolic syndrome: a randomized double-blind, placebo-controlled phase 2 trial. Nat Med 2021; 27(7): 1272–1279

    Article  CAS  PubMed  Google Scholar 

  95. Rinott E, Youngster I, Yaskolka Meir A, Tsaban G, Zelicha H, Kaplan A, Knights D, Tuohy K, Fava F, Scholz MU, Ziv O, Reuven E, Tirosh A, Rudich A, Blüher M, Stumvoll M, Ceglarek U, Clement K, Koren O, Wang DD, Hu FB, Stampfer MJ, Shai I. Effects of diet-modulated autologous fecal microbiota transplantation on weight regain. Gastroenterology 2021; 160(1): 158–173.e10

    Article  CAS  PubMed  Google Scholar 

  96. de Groot PF, Frissen MN, de Clercq NC, Nieuwdorp M. Fecal microbiota transplantation in metabolic syndrome: History, present and future. Gut Microbes 2017; 8(3): 253–267

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Ma Y, Xu X, Li M, Cai J, Wei Q, Niu H. Gut microbiota promote the inflammatory response in the pathogenesis of systemic lupus erythematosus. Mol Med 2019; 25(1): 35

    Article  PubMed  PubMed Central  Google Scholar 

  98. Ma Y, Niu H. In Gut Microbiota Can Promote the Inflammatory Response in The Pathogenesis of Systemic Lupus Erythematosus. Summary of the 13th National Conference on Immunology, 2018

  99. Zhang Y, Liu Q, Yu Y, Wang M, Wen C, He Z. Early and short-term interventions in the gut microbiota affects lupus severity, progression, and treatment in MRL/lpr mice. Front Microbiol 2020; 11: 628

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Danne C, Rolhion N, Sokol H. Recipient factors in faecal microbiota transplantation: one stool does not fit all. Nat Rev Gastroenterol Hepatol 2021; 18(7): 503–513

    Article  PubMed  Google Scholar 

  101. Abbasi J. Are bacteria transplants the future of eczema therapy? JAMA 2018; 320(11): 1094–1095

    Article  PubMed  Google Scholar 

  102. Nakatsuji T, Hata TR, Tong Y, Cheng JY, Shafiq F, Butcher AM, Salem SS, Brinton SL, Rudman Spergel AK, Johnson K, Jepson B, Calatroni A, David G, Ramirez-Gama M, Taylor P, Leung DYM, Gallo RL. Development of a human skin commensal microbe for bacteriotherapy of atopic dermatitis and use in a phase 1 randomized clinical trial. Nat Med 2021; 27(4): 700–709

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work is supported by CAMS Innovation Fund for Medical Sciences (No. 2021-I2M-1-059) and the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences (Nos. 2020-RC320-003 and 2021-RC320-001).

Author information

Authors and Affiliations

  1. Key Laboratory of Basic and Translational Research on Immune-Mediated Skin Diseases, Chinese Academy of Medical Sciences, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, 210042, China

    Yijing Zhan, Qianmei Liu, Bo Zhang & Qianjin Lu

  2. Department of Dermatology, The Second Xiangya Hospital of Central South University, Institute of Dermatology and Venereology of Central South University, Hunan Clinical Medicine Research Center for Major Skin Diseases and Skin Health, Changsha, 410011, China

    Xin Huang

Authors
  1. Yijing Zhan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Qianmei Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bo Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xin Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Qianjin Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Xin Huang or Qianjin Lu.

Ethics declarations

Yijing Zhan, Qianmei Liu, Bo Zhang, Xin Huang, and Qianjin Lu declare that they have no conflicts of interest. This manuscript is a review article and does not involve a research protocol requiring approval by the relevant institutional review board or ethics committee.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhan, Y., Liu, Q., Zhang, B. et al. Recent advances in systemic lupus erythematosus and microbiota: from bench to bedside. Front. Med. 16, 686–700 (2022). https://doi.org/10.1007/s11684-022-0957-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11684-022-0957-7

Keywords

Search

Navigation