Management of familial Mediterranean fever by colchicine does not normalize the altered profile of microbial long chain fatty acids in the human metabolome

Abstract

In our previous works we established that in an autoinflammatory condition, familial Mediterranean fever (FMF), the gut microbial diversity is specifically restructured, which also results in the altered profiles of microbial long chain fatty acids (LCFAs) present in the systemic metabolome. The mainstream management of the disease is based on oral administration of colchicine to suppress clinical signs and extend remission periods and our aim was to determine whether this therapy normalizes the microbial LCFA profiles in the metabolome as well. Unexpectedly, the treatment does not normalize these profiles. Moreover, it results in the formation of new distinct microbial LCFA clusters, which are well separated from the corresponding values in healthy controls and FMF patients without the therapy. We hypothesize that the therapy alters the proinflammatory network specific for the disease, with the concomitant changes in gut microbiota and the corresponding microbial LCFAs in the metabolome.

Keywords: colchicine; discriminant function analysis; familial Mediterranean fever; gas chromatography/mass spectrometry (GC/MS); metabolome; microbial long chain fatty acids.

Figure 1

Scatterplot of DA model based on systemic concentration of microbial components of the metabolome. Number of variables in the model—30 and grouping consists of five groups. Root 1, 2—discriminant functions 1 and 2 (1st and 2nd canonical roots). , Healthy subjects; , FMF patients in attack period without colchicine treatment; , FMF patients in attack period under colchicine treatment; , FMF patients in remission period without colchicine treatment; , FMF patients in remission period under colchicine treatment; , group centroid.