Specific changes in faecal microbiota are associated with familial Mediterranean fever

Samuel Deshayes (1, 2, 3, 4, 5, 6) , Soraya Fellahi (5, 3, 7, 8) , Jean-Philippe Bastard (5, 3, 7) , Jean-Marie Launay (9, 10) , Jacques Callebert (9, 10) , Thibault Fraisse (5, 8) , David Buob (5) , Jean-Jacques Boffa (5, 8) , Irina Giurgea (11, 12, 11) , Charlotte Dupont (5, 3, 8) , Sarah Jegou (3, 4, 8) , Marjolene Straube (3, 4, 8) , Alexandre Karras (13) , Achille Aouba (14, 2, 1) , Gilles Grateau (5, 8) , Harry Sokol (15, 4, 3, 8, 16) , Sophie Georgin-Lavialle (5, 8)

1 UNICAEN - Université de Caen Normandie
2 Service de médecine interne [CHU Caen]
3 CRSA - Centre de Recherche Saint-Antoine
4 CHU Saint-Antoine [AP-HP]
5 CHU Tenon [AP-HP]
6 NU - Normandie Université
7 ICAN - Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases
8 SU - Sorbonne Université
9 BioCANVAS / U942 - Biomarqueurs CArdioNeuroVASCulaires
10 Hôpital Lariboisière
11 CHU Trousseau [APHP]
12 U933 - Maladies génétiques d'expression pédiatrique
13 Service de Néphrologie et Hémodialyse [CHU HEGP]
14 CHU Caen
15 MICALIS - MICrobiologie de l'ALImentation au Service de la Santé
16 Université Paris-Saclay

OBJECTIVES: Familial Mediterranean fever (FMF) can be complicated by AA amyloidosis (AAA), though it remains unclear why only some patients develop amyloidosis. We examined the gut microbiota composition and inflammatory markers in patients with FMF complicated or not by AAA. METHODS: We analysed the gut microbiota of 34 patients with FMF without AAA, 7 patients with FMF with AAA, 19 patients with AAA of another origin, and 26 controls using 16S ribosomal RNA gene sequencing with the Illumina MiSeq platform. Associations between bacterial taxa and clinical phenotypes were evaluated using multivariate association with linear models statistical method. Blood levels of interleukin (IL)-1β, IL-6, tumour necrosis factor-α and adipokines were assessed by ELISA; indoleamine 2,3-dioxygenase (IDO) activity was determined by high-performance liquid chromatography. RESULTS: Compared with healthy subjects, specific changes in faecal microbiota were observed in FMF and AAA groups. Several operational taxonomic units (OTUs) were associated with FMF. Moreover, two OTUs were over-represented in FMF-related AAA compared with FMF without AAA. Additionally, higher adiponectin levels and IDO activity were observed in FMF-related AAA compared with FMF without AAA (p<0.05). CONCLUSION: The presence of specific changes in faecal microbiota in FMF and in FMF-related AAA suggests that intestinal microorganisms may play a role in the pathogenesis of these diseases. These findings may offer an opportunity to use techniques for gut microbiota manipulation.

Mots clés: indoleamine 2 3-dioxygenase; familial Mediterranean fever; microbiota; AA amyloidosis; adipokines

Domaines: Hépatologie et Gastroentérologie; Rhumatologie et système ostéo-articulaire

Samuel Deshayes, Soraya Fellahi, Jean-Philippe Bastard, Jean-Marie Launay, Jacques Callebert, et al.. Specific changes in faecal microbiota are associated with familial Mediterranean fever. Annals of the Rheumatic Diseases, 2019, 78 (10), pp.1398-1404. ⟨10.1136/annrheumdis-2019-215258⟩. ⟨hal-02291701⟩