Marion Delplanque1,2,3,†, Nicolas Benech2,3,†, Nathalie Rolhion2,3, Cyriane Oeuvray2,3, Marjolène Straube2,3, Chloé Galbert2,3, Loic Brot2,3, Thomas Henry 4 , Yvan Jamilloux4 , Le´ a Savey1 , Gilles Grateau1 , Harry Sokol 2,3,5, Sophie Georgin-Lavialle1,2,3,*
Link to article: https://pubmed.ncbi.nlm.nih.gov/37402619/
Summary:
The intestinal microbiota has attracted growing interest in recent years due to its involvement in a number of diseases. In Familial Mediterranean Fever (FMF), its role was suspected because certain digestive bacterial infections caused attacks of the disease, such as Helicobacter pylori in the stomach. With the help of Professors Georgin-Lavialle and Sokol from the "Microbiota and Immunity" Avenir Team (INSERM U938 unit), and all the patients and their relatives who agreed to take part, Dr Marion Delplanque, Assistant Clinical Head of the FMF National Reference Centre at Tenon Hospital, conducted research over a year to compare the composition of the intestinal microbiota of patients with FMF with a control group of healthy subjects. The technique used to study the genetic content of the intestine is called metagenomics; it enables the microorganisms present in the faeces to be identified.The faecal microbiota of 119 patients with FMF was compared with that of 61 healthy subjects. Of the FMF patients, 88 carried 2 pathogenic mutations in the MEFV gene and 31 carried a single mutation. Twenty-seven patients (22.7%) were resistant to colchicine, 17 had inflammatory amyloidosis, also known as AA amyloidosis (14.2%) and 10 were on anti-interleukin-1 biotherapy.
We demonstrated an imbalance in the intestinal flora (known as dysbiosis) in patients with FMF compared with healthy subjects. Bacterial diversity, measured by the number of different species present in the intestine, was reduced in patients with FMF. In addition, certain inflammation-promoting bacteria were predominant in FMF patients. In patients with severe FMF, defined by the presence of AA amyloidosis and/or colchicine resistance, inflammation-promoting bacteria were significantly more abundant than in less severe patients. Finally, the composition of the microbiota differed according to the response to colchicine: colchicine-resistant patients had a different structure and composition to colchicine-sensitive patients, and the connectivity of their bacterial network was reduced.
Overall, this is the most important study to date of stool composition in FMF. It confirms that there is an imbalance in the composition of the intestinal flora (or dysbiosis) in patients with FMF compared with healthy controls. Further work is needed to determine whether the intestinal flora could be a therapeutic target in FMF, particularly in the case of colchicine-resistant forms or severe complications such as AA amyloidosis.
Référence :
Delplanque M et al. Gut microbiota alterations are associated with phenotype and genotype in familial Mediterranean fever. Rheumatology (Oxford). 2023 Jul 4 (ahead print). PMID : 37402619
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