{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T20:53:10Z","timestamp":1788900790504,"version":"build-2803163510"},"reference-count":18,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T00:00:00Z","timestamp":1773792000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease worldwide and a key-model to illustrate dysregulation of innate immunity, etiologically determined by pathogenic variants in the\n                    <jats:italic>MEFV<\/jats:italic>\n                    gene, encoding pyrin, leading to uncontrolled interleukin-1\u03b2 and interleukin-18 release. Despite its genetic basis, FMF shows marked clinical heterogeneity in all-aged patients, mostly in children, suggesting a role of potential environmental modifiers which are far to be exactly unraveled. Recent medical literature has increasingly illuminated the importance of gut microbiota in maintaining overall health and immune functions, and its contribution has been claimed also to explain both FMF inflammatory activity and heterogeneous disease expression. This narrative review summarizes current evidence on the interaction between gut microbiota and FMF, with a specific focus on differences between children and adults. Pediatric studies dedicated to FMF have reported intestinal dysbiosis in terms of reduced microbial diversity and depletion of short-chain fatty acid-producing bacteria, with subsequent enrichment of pro-inflammatory taxa: such alteration could modulate pyrin-inflammasome activation and contribute to systemic inflammation, disease phenotype, and response to colchicine or to other drugs specifically used in colchicine-resistant FMF. Geographic and lifestyle factors may shape intestinal microbiota composition early in life, reinforcing the relevance of gut flora and confirming its activity as a crucial tessera to determine FMF sceneries, mostly in children, and a potential target for future add-on therapeutic strategies. In addition, colchicine therapy appears to partially remodel the gut microbiome, empowering a local beneficial anti-inflammatory microbial profile.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1814103","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T06:56:07Z","timestamp":1773816967000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Gut microbiota alliance to shape sceneries of familial Mediterranean fever: a scoping review detailing difference between children and adults"],"prefix":"10.3389","volume":"17","author":[{"given":"Camilla Maria","family":"Pisa","sequence":"first","affiliation":[{"name":"Pediatric Clinic, University Hospital, Department of Medicine and Surgery, University of Parma","place":["Parma, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo","family":"Verrone","sequence":"additional","affiliation":[{"name":"Pediatric Clinic, University Hospital, Department of Medicine and Surgery, University of Parma","place":["Parma, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martha","family":"Mazuy","sequence":"additional","affiliation":[{"name":"Pediatric Clinic, University Hospital, Department of Medicine and Surgery, University of Parma","place":["Parma, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Ientile","sequence":"additional","affiliation":[{"name":"Pediatric Clinic, University Hospital, Department of Medicine and Surgery, University of Parma","place":["Parma, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donato","family":"Rigante","sequence":"additional","affiliation":[{"name":"Department of Life Sciences and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS","place":["Rome, Italy"]},{"name":"Periodic Fevers Research Center, Universit\u00e0 Cattolica Sacro Cuore","place":["Rome, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanna","family":"Esposito","sequence":"additional","affiliation":[{"name":"Pediatric Clinic, University Hospital, Department of Medicine and Surgery, University of Parma","place":["Parma, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1007\/s11916-024-01345-0","article-title":"Familial Mediterranean fever (FMF): emerging concepts in diagnosis, pain management, and novel treatment options: a narrative review","volume":"29","author":"Kaye","year":"2025","journal-title":"Curr Pain Headache Rep"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2135380100","article-title":"Pyrin binds the PSTPIP1\/CD2BP1 protein, defining familial Mediterranean fever and PAPA syndrome as disorders in the same pathway","volume":"100","author":"Shoham","year":"2003","journal-title":"Proc Natl Acad Sci USA"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1080\/1744666X.2017.1280396","article-title":"A systematic approach to autoinflammatory syndromes: a spelling booklet for the beginner","volume":"13","author":"Rigante","year":"2017","journal-title":"Expert Rev Clin Immunol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"3","DOI":"10.4274\/balkanmedj.galenos.2025.2025-11-133","article-title":"Familial Mediterranean fever: a comprehensive review of pathogenesis, genetics, and epigenetic regulation","volume":"43","author":"Ugurlu","year":"2026","journal-title":"Balkan Med J"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.5152\/TurkArchPediatr.2024.24188","article-title":"Familial Mediterranean fever in childhood","volume":"59","author":"Kisla Ekinci","year":"2024","journal-title":"Turk Arch Pediatr"},{"key":"B6","doi-asserted-by":"publisher","first-page":"999","DOI":"10.3748\/wjg.v31.i5.99913","article-title":"Unlocking the secrets of the human gut microbiota: comprehensive review on its role in different diseases","volume":"31","author":"Paul","year":"2025","journal-title":"World J Gastroenterol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2026.103036","article-title":"Gut microbiota-derived metabolites as immune modulators in aging and age-related chronic inflammatory diseases","volume":"116","author":"Chen","year":"2026","journal-title":"Ageing Res Rev"},{"key":"B8","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1111\/imr.12907","article-title":"The pyrin inflammasome and the Yersinia effector interaction","volume":"297","author":"Malik","year":"2020","journal-title":"Immunol Rev"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kead322","article-title":"Gut microbiota alterations are associated with phenotype and genotype in familial Mediterranean fever","volume":"63","author":"Delplanque","year":"2024","journal-title":"Rheumatol (Oxford)"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2019-215258","article-title":"Specific changes in faecal microbiota are associated with familial Mediterranean fever","volume":"78","author":"Deshayes","year":"2019","journal-title":"Ann Rheum Dis"},{"key":"B11","doi-asserted-by":"publisher","first-page":"47","DOI":"10.55563\/clinexprheumatol\/olvbyd","article-title":"Microbiome is not linked to clinical disease severity of familial Mediterranean fever in an international cohort of children","volume":"39","author":"Ozen","year":"2021","journal-title":"Clin Exp Rheumatol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1007\/s12602-021-09779-3","article-title":"The effect of immunobiotic\/psychobiotic Lactobacillus acidophilus strain INMIA 9602 Er 317\/402 Narine on gut Prevotella in familial Mediterranean fever: gender-associated effects","volume":"13","author":"Pepoyan","year":"2021","journal-title":"Probiotics Antimicrob Proteins"},{"key":"B13","article-title":"The pharmacologic basis of treatment with colchicine in children with familial Mediterranean fever","volume":"10","author":"Rigante","year":"2006","journal-title":"Eur Rev Med Pharmacol Sci"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2024.105454","article-title":"Involvement of Mediterranean fever gene mutations in colchicine-responsive enterocolitis: a retrospective cohort study","volume":"110","author":"Nakase","year":"2024","journal-title":"EBioMedicine"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2013.00002","article-title":"Management of familial Mediterranean fever by colchicine does not normalize the altered profile of microbial long chain fatty acids in the human metabolome","volume":"3","author":"Ktsoyan","year":"2013","journal-title":"Front Cell Infect Microbiol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/939847","article-title":"Biological treatments: new weapons in the management of monogenic autoinflammatory disorders","volume":"2013","author":"Vitale","year":"2013","journal-title":"Mediators Inflammation"},{"key":"B17","first-page":"1","article-title":"The protean visage of systemic autoinflammatory syndromes: a challenge for inter-professional collaboration","volume":"14","author":"Rigante","year":"2010","journal-title":"Eur Rev Med Pharmacol Sci"},{"key":"B18","doi-asserted-by":"publisher","first-page":"600","DOI":"10.1016\/j.chom.2018.09.009","article-title":"Compositional and temporal changes in the gut microbiome of pediatric ulcerative colitis patients are linked to disease course","volume":"24","author":"Schirmer","year":"2018","journal-title":"Cell Host Microbe"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1814103\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T06:56:09Z","timestamp":1773816969000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1814103\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,18]]},"references-count":18,"alternative-id":["10.3389\/fimmu.2026.1814103"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1814103","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,18]]},"article-number":"1814103"}}