Intestinal microbiota alterations link subclinical inflammation and clinical phenotypes in familial Mediterranean fever

Introduction Familial Mediterranean fever (FMF) is an autoinflammatory disease caused by mutations in the Mediterranean fever ( MEFV ) gene. Although FMF is classically associated with serosal inflammation, emerging evidence suggests intestinal involvement. We aimed to investigate subclinical intestinal inflammation in patients with FMF by assessing fecal calprotectin (FCP) levels and intestinal microbial and fecal metabolic profiles. Methods Thirty patients with FMF from three hospitals were stratified into the FCP-high (>94 μg/g) and FCP-low (≤94 μg/g) groups. For intestinal microbiota analysis, patients with FMF were also compared with healthy controls and patients with inflammatory bowel disease unclassified (IBDU) from previous multicenter studies. Results Elevated FCP levels were detected in 26.7% patients. The FCP-high group had lower hemoglobin levels and a trend toward lower albumin levels. Compared with healthy controls, patients with FMF showed reduced alpha diversity and differences in overall microbiota composition. A higher relative abundance of Bifidobacterium longum and lower relative abundances of Faecalibacterium , Blautia , and Blautia obeum showed exploratory associations with arthritis, as well as lower albumin and hemoglobin levels. The FCP-high group showed greater depletion in the relative abundance of Blautia and nominally higher fecal 2-amino-2-methyl-1-propanol levels. The relative abundance of Lactobacillus , Streptococcus , and Enterococcus showed stepwise increased from healthy controls to the FCP-low FMF, FCP-high FMF, and IBDU with MEFV mutation groups, whereas that of Fusicatenibacter and Agathobacter showed stepwise decreased across these groups. Discussion This exploratory study identified associations among FMF, elevated FCP, and alterations in the intestinal microbiota. Elevated FCP in a subset of clinically remitted patients may suggest possible subclinical intestinal inflammatory activity.