Review Articles
Vol. 18 No. 1 (2026): Mediterranean Journal of Hematology and Infectious Diseases
HIGHLIGHTS ON THE CONTRIBUTION OF GUT MICROBIOTA TO IMMUNE-MEDIATED DISEASES IN CHILDHOOD
Gut microbiota in childhood immune-mediated diseases
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All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Published: February 28, 2026
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The gut microbiota, a huge community of symbiont microorganisms inhabiting our gut, has been recognized as a key-lever for human health, shaping resiliency for immune system development and being essential for immunologic homeostasis during the entire life course. Gut microbiota composition influences both initiation and/or perpetuation of intestinal inflammation, but recent research has highlighted its contribution to both rising and progression of protean non-intestinal inflammatory diseases: indeed, a perturbation of such microbiota during critical developmental stages like early childhood can directly condition many cellular dynamics and impact long-term health. This narrative review explores the interactions between gut microbiota, physiologic healthy equilibrium, dysbiosis, and immune-mediated non-intestinal inflammatory diseases occurring in childhood like inflammasome-based disorders, juvenile idiopathic arthritis, Kawasaki disease, and IgA vasculitis, focusing on how microbial changes may alter disease outcome and suggesting potentially novel therapeutic approaches. Additionally, this review examines the evolution of immune recognition mechanisms and their role in maintaining gut microbiota-host mutualism as a result of millennia of human co-evolution with their microbial counterpart.
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Cai J, Sun L, Gonzalez F. Gut microbiota-derived bile acids in intestinal immunity, inflammation, and tumorigenesis. Cell Host Microbe 2022;3:289-300. https://doi.org/10.1016/j.chom.2022.02.004 PMid: 35271802
Wu H, Tremaroli V, Schmidt C, et al. Bäckhed, F. The gut microbiota in prediabetes and diabetes: a population-based cross-sectional study. Cell Metab 2020;32:379-90.e3. https://doi.org/10.1016/j.cmet.2020.06.011 PMid: 32652044
Dzik JM. The ancestry and cumulative evolution of immune reactions. Acta Biochim Pol 2010;57:443-66. PMid: 21046016
Janeway CA, Medzhitov R. Innate immune recognition. Annu Rev Immunol 2002;20:197-216. https://doi.org/10.1146/annurev.immunol.20.083001.084359 PMid: 11861602
Li D, Wu M. Pattern recognition receptors in health and diseases. Signal Transuct Target Ther 2021;6:291.
doi: 10.1038/s41392-021-00687-0 PMid: 34344870
Hoffmann JA, Reichhart JM. Drosophila innate immunity: an evolutionary perspective. Nat Immunol 2002;3:121-6. https://doi.org/10.1038/ni0202-121 PMid: 11812988
Litman GW, Cannon JP, Dishaw LJ. Reconstructing immune phylogeny: new perspectives. Nat Rev Immunol 2005;5:866-79. https://doi.org/10.1038/nri1712 PMid: 16261174
Pancer Z, Cooper MD. The evolution of adaptive immunity. Annu Rev Immunol 2006;24:497-518. https://doi.org/10.1146/annurev.immunol.24.021605.090542 PMid: 16551257
Hand TW, Vujkovic-Cvijin I, Ridaura VK, et al. Linking the microbiota, chronic disease, and the immune system. Trends Endocrinol Metab 2016;27:831-43. https://doi.org/10.1016/j.tem.2016.08.003 PMid: 27623245
Belkaid Y, Hand TW. Role of the microbiota in immunity and inflammation. Cell 2014;157:121-31. https://doi.org/10.1016/j.cell.2014.03.011 PMid: 24679531
McFall-Ngai M. Adaptive immunity: care for the community. Nature 2007;445(7124):153. https://doi.org/10.1038/445153a PMid: 17215830
Capaldo CT, Beeman N, Hilgarth RS, et al. IFN-γ and TNF-α-induced GBP-1 inhibits epithelial cell proliferation through suppression of β-catenin/TCF signaling. Mucosal Immunol 2012;5:681-90. https://doi.org/10.1038/mi.2012.41 PMId: 22692453
Gueddouri D, Caüzac M, Fauveau V, et al. Insulin resistance per se drives early and reversible dysbiosis-mediated gut barrier impairment and bactericidal dysfunction. Mol Metab 2022;57:101438. https://doi.org/10.1016/j.molmet.2022.101438 PMid: 35007789
Camilleri M. Leaky gut: mechanisms, measurement and clinical implications in humans. Gut 2019;68:1516-26. https://doi.org/10.1136/gutjnl-2019-318427 PMid: 31076401
Guittar J, Shade A. Trait-based community assembly and succession of the infant gut microbiome. Nat Commun 2019;10:512. https://doi.org/10.1038/s41467-019-08377-w PMid: 30710083
Faith JJ, Guruge JL, Charbonneau M, et al. The long-term stability of the human gut microbiota. Science 2013;341:1237439. https://doi.org/10.1126/science.1237439 PMid: 23828941
Liberty IA, Hanifah L, Rachmat HF, et al. Implication of taxonomic abundance of gut microbiota in prediabetes: a systematic review. Front Nutr 2025;12:1577528. https://doi.org/10.3389/fnut.2025.1577528 PMid: 40308637
He M, Liu L, Li Y, et al. Formation of gut microbiota and application of microecological regulators in children. Transl Pediatr 2025;14:2023-41. https://doi.org/10.21037/tp-2025-303 PMid: 40949907
Zhou W, Sailani MR, Contrepois K, et al. Longitudinal multi-omics of host-microbe dynamics in prediabetes. Nature 2019;569:663-71. https://doi.org/10.1038/s41586-019-1236-x PMid: 31142858
Cantarini L, Iacoponi F, Lucherini OM, et al. Validation of a diagnostic score for the diagnosis of autoinflammatory diseases in adults. Int J Immunopathol Pharmacol 2011;24:695-702. https://doi.org/10.1177/039463201102400315 PMid: 21978701
Sarı İ, Birlik M, Kasifoğlu T. Familial Mediterranean fever: an updated review. Eur J Rheumatol 2014;1:21-33. https://doi.org/10.5152/eurjrheum.2014.006 PMid: 27708867
Rigante D, Frediani B, Galeazzi M, et al. From the Mediterranean to the sea of Japan: the transcontinental odyssey of autoinflammatory diseases. Biomed Res Int 2013;2013:485103. https://doi.org/10.1155/2013/485103 PMid: 23971037
Ozen S, Lutz HL, Rivera VM, et al. Microbiome is not linked to clinical disease severity of familial Mediterranean fever in an international cohort of children. Clin Exp Rheumatol 2021;39 Suppl 132(5):102-8. https://doi.org/10.55563/clinexprheumatol/olvbyd PMid: 34251310
Delplanque M, Benech N, Rolhion N, et al. Gut microbiota alterations are associated with phenotype and genotype in familial Mediterranean fever. Rheumatology (Oxford) 2024;63:1039-48. https://doi.org/10.1093/rheumatology/kead322 PMid: 37402619
Pepoyan AZ, Balayan MH, Manvelyan AM, et al. Lactobacillus acidophilus INMIA 9602 Er-2 strain 317/402 probiotic regulates growth of commensal Escherichia coli in gut microbiota of familial Mediterranean fever disease subjects. Lett Appl Microbiol 2017;64:254-60. https://doi.org/10.1111/lam.12722 PMid: 28140472
Pepoyan A, Balayan M, Manvelyan A, et al. Probiotic Lactobacillus acidophilus strain INMIA 9602 Er 317/402 administration reduces the numbers of Candida albicans and abundance of enterobacteria in the gut microbiota of familial Mediterranean fever patients. Front Immunol 2018;9:1426. https://doi.org/10.3389/fimmu.2018.01426 PMid: 29997616
Pepoyan E, Marotta F, Manvelyan A, et al. Placebo-resistant gut bacteria: Akkermansia muciniphila spp. and familial Mediterranean fever disease. Front Cell Infect Microbiol 2024;14:1336752. https://doi.org/10.3389/fcimb.2024.1336752 PMid: 38465231
Rigante D. The protean visage of systemic autoinflammatory syndromes: a challenge for inter-professional collaboration. Eur Rev Med Pharmacol Sci 2010;14:1-18. PMid: 20184084
Mafra D, Alvarenga L, Cardozo LFMF, et al. Gut microbiota and NLRP3 inflammasome activation in hemodialysis patients: exploring the link with systemic inflammation. Mol Biol Rep 2025;52:465. https://doi.org/10.1007/s11033-025-10562-8 PMid: 40387945
Deng L, He R, Mao J, et al. Modulation of NLRP3 inflammasome and uric acid metabolism by small molecule pectin from Premna ligustroides Hemsl leaves: Implications for hyperuricemia management. Int J Biol Macromol 2025;331(Pt 1):148214. https://doi.org/10.1016/j.ijbiomac.2025.14821 PMid: 41075904
Rigante D. A systematic approach to autoinflammatory syndromes: a spelling booklet for the beginner. Expert Rev Clin Immunol 2017;13:571-97. https://doi.org/10.1080/1744666X.2017.1280396 PMid: 28064547
Eeckhout E, Asaoka T, Van Gorp H, et al. The autoinflammation-associated NLRC4V341A mutation increases microbiota-independent IL-18 production but does not recapitulate human autoinflammatory symptoms in mice. Front Immunol 2023;14:1272639. https://doi.org/10.3389/fimmu.2023.1272639 PMid: 38090573
Bracaglia C, Marucci G, Del Chierico F, et al. Microbiota transplant to control inflammation in a patient with NLRC4 gain-of-function–induced disease. J Allergy Clin Immunol 2023;152:302-3. https://doi.org/10.1016/j.jaci.2023.03.031 PMid: 37178069
Verwoerd A, ter Haar NM, de Roock S, et al. The human microbiome and juvenile idiopathic arthritis. Pediatr Rheumatol Online J 2016;14:55. https://doi.org/10.1186/s12969-016-0114-4 PMid: 27650128
Rigante D. The fresco of autoinflammatory diseases from the pediatric perspective. Autoimmun Rev 2012;11:348-56. https://doi.org/10.1016/j.autrev.2011.10.008 PMid: 22024500
Han EJ, Ahn JS, Chae YJ, et al. Immunomodulatory roles of Faecalibacterium prausnitzii and Akkermansia muciniphila in autoimmune diseases: mechanistic insights and therapeutic potential. Clin Rev Allergy Immunol 2025;68:77. https://doi.org/10.1007/s12016-025-09093-8 PMid: 40759811
Tejesvi MV, Arvonen M, Kangas SM, et al. Faecal microbiome in new‐onset juvenile idiopathic arthritis. Eur J Clin Microbiol Infect Dis 2016;35:363-70. https://doi.org/10.1007/s10096-015-2548-x PMid: 26718942
Aggarwal A, Sarangi AN, Gaur P, et al. Gut microbiome in children with enthesitis-related arthritis in a developing country and the effect of probiotic administration. Clin Exp Immunol 2017;187:480-9. https://doi.org/10.1111/cei.12900 PMid: 27861762
van Dijkhuizen EHP, Del Chierico F, Malattia C, et al. Microbiome analytics of the gut microbiota in patients with juvenile idiopathic arthritis: a longitudinal observational cohort study. Arthritis Rheumatol 2019;71:1000-10. https://doi.org/10.1002/art.40827 PMid: 30592383
Rigante D. Autoinflammatory syndromes behind the scenes of recurrent fevers in children. Med Sci Monit 2009;15:RA179-87. PMid: 19644432
Rigante D. The broad-ranging panorama of systemic autoinflammatory disorders with specific focus on acute painful symptoms and hematologic manifestations in children. Mediterr J Hematol Infect Dis 2018;10(1):e2018067. https://doi.org/10.4084/MJHID.2018.067 PMid: 30416699
Dong YQ, Wang W, Li J, et al. Characterization of microbiota in systemic-onset juvenile idiopathic arthritis with different disease severities. World J Clin Cases 2019;7:2734-45. https://doi.org/10.12998/wjcc.v7.i18.2734 PMid: 31616689
Gao B, Wang Z, Wang K, et al. Relationships among gut microbiota, plasma metabolites, and juvenile idiopathic arthritis: a mediation Mendelian randomization study. Front Microbiol 2024;15:1363776. https://doi.org/10.3389/fmicb.2024.1363776 PMid: 38605717
Picchianti-Diamanti A, Panebianco C, Salemi S, et al. Analysis of gut microbiota in rheumatoid arthritis patients: disease-related dysbiosis and modifications induced by etanercept. Int J Mol Sci 2018;19:2938. https://doi.org/10.3390/ijms19102938 PMid: 30261687
Federico G, Rigante D, Pugliese AL, et al. Etanercept induces improvement of arthropathy in chronic infantile neurological cutaneous articular (CINCA) syndrome. Scand J Rheumatol 2003;32:312-4. https://doi.org/10.1080/03009740310003974 PMid: 14690147
Cantarini L, Rigante D, Lucherini OM, et al. Role of etanercept in the treatment of tumor necrosis factor receptor-associated periodic syndrome: personal experience and review of the literature. Int J Immunopathol Pharmacol 2010;23:701-7. https://doi.org/10.1177/039463201002300303 PMid: 20943039
De Rosa G, Pardeo M, Rigante D. Current recommendations for the pharmacologic therapy in Kawasaki syndrome and management of its cardiovascular complications. Eur Rev Med Pharmacol Sci 2007;11:301-8. PMid: 18074939
Rigante D, Valentini P, Rizzo D, et al. Responsiveness to intravenous immunoglobulins and occurrence of coronary artery abnormalities in a single-center cohort of Italian patients with Kawasaki syndrome. Rheumatol Int 2010;30:841-6. https://doi.org/10.1007/s00296-009-1337-1 PMid: 20049445
Rigante D. Kawasaki disease as the immune-mediated echo of a viral infection. Mediterr J Hematol Infect Dis 2020;12(1):e2020039. https://doi.org/10.4084/MJHID.2020.039 PMid: 32670517
Rigante D, Tarantino G, Valentini P. Non-infectious makers of Kawasaki syndrome: tangible or elusive triggers? Immunol Res 2016;64:51-4. https://doi.org/10.1007/s12026-015-8679-4 PMid: 26232895
Esposito S, Polinori I, Rigante D. The gut microbiota-host partnership as a potential driver of Kawasaki syndrome. Front Pediatr 2019;7:124. https://doi.org/10.3389/fped.2019.00124 PMid: 31024869
Yang Q, Kang Y, Tang W, et al. Interplay of gut microbiota in Kawasaki disease: role of gut microbiota and potential treatment strategies. Future Microbiol 2025;20:357-69. https://doi.org/10.1080/17460913.2025.2469432 PMid: 40013895
Teramoto Y, Akagawa S, Hori SI, et al. Dysbiosis of the gut microbiota as a susceptibility factor for Kawasaki disease. Front Immunol 2023;14:1268453. https://doi.org/10.3389/fimmu.2023.1268453 PMid: 38022552
Gül A. Pathogenesis of Behçet's disease: autoinflammatory features and beyond. Semin Immunopathol 2015;37:413-8. https://doi.org/10.1007/s00281-015-0502-8 PMId: 26068404
Consolandi C, Turroni S, Emmi G, et al. Behçet's syndrome patients exhibit specific microbiome signature. Autoimmun Rev 2015;14:269-76. https://doi.org/10.1016/j.autrev.2014.11.009 PMid: 25435420
Chen JY, Mao JH. Henoch-Schönlein purpura nephritis in children: incidence, pathogenesis and management. World J Pediatr 2015;11:29-34. https://doi.org/10.1007/s12519-014-0534-5 PMid: 25557596
Wen M, Dang X, Feng S, et al. Integrated analyses of gut microbiome and host metabolome in children with Henoch-Schönlein purpura. Front Cell Infect Microbiol 2022;11:796410. https://doi.org/10.3389/fcimb.2021.796410 PMid: 35145922
Wang X, Zhang L, Wang Y, et al. Gut microbiota dysbiosis is associated with Henoch-Schönlein purpura in children. Int Immunopharmacol 2018;58:1-8. https://doi.org/10.1016/j.intimp.2018.03.003 PMId: 29525681
Liang M, Deng Z, Wu W, et al. Study on the correlation between intestinal flora and cytokines in children with Henoch-Schönlein purpura. Cytokine 2025;191:156959. https://doi.org/10.1016/j.cyto.2025.156959 PMid: 40373421
Liang Y, Zhao C, Zhao L, et al. Taxonomic and functional shifts of gut microbiome in immunoglobulin A vasculitis children and their mothers. Front Pediatr 2024;12:1356529. https://doi.org/10.3389/fped.2024.1356529 PMid: 38410769
Mazziotta C, Tognon M, Martini F, et al. Probiotics mechanism of action on immune cells and beneficial effects on human health. Cells 2023;12:184. https://doi.org/10.3390/cells12010184 PMid: 36611977
Bettocchi S, Comotti A, Elli M, et al. Probiotics and fever duration in children with upper respiratory tract infections: a randomized clinical trial. JAMA Netw Open 2025;8:e2500669. https://doi.org/10.1001/jamanetworkopen.2025.0669 PMid: 40085083
Bermudez-Brito M, Plaza-Díaz J, Muñoz-Quezada S, et al. Probiotic mechanisms of action. Ann Nutr Metab 2012;61:160-74. https://doi.org/10.1159/000342079 PMid: 23037511
Hao Q, Dong BR, Wu T. Probiotics for preventing acute upper respiratory tract infections. Cochrane Database Syst Rev 2022;8:CD006895. https://doi.org/10.1002/14651858.CD006895.pub4 PMid: 32670517
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“HIGHLIGHTS ON THE CONTRIBUTION OF GUT MICROBIOTA TO IMMUNE-MEDIATED DISEASES IN CHILDHOOD: Gut microbiota in childhood immune-mediated diseases” (2026) Mediterranean Journal of Hematology and Infectious Diseases, 18(1), p. e2026025. doi:10.4084/MJHID.2026.025.
Copyright (c) 2026 Donato Rigante
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