Fig. 4

MCII+ and MCII− groups display significantly different fold-changes in microbial taxa and biochemical pathways from baseline to follow-up. a Eight microbial taxa showed significant differences in fold-changes (from baseline to follow-up) between the MCII+ and MCII– patient groups (P < 0.05, MLRM). Among these eight, relative abundances diverged in opposite directions in five taxa: Gammaproteobacteria and Oscillibacter increased in relative abundance from baseline to follow-up in the MCII+ patient group, but decreased in MCII– patient group; alternatively, the relative abundances of Coprococcus, Ruminococcus, and Anaerotruncus colihominis decreased at the follow-up visit in MCII+ patients, but increased in MCII– patients. b Seven MetaCyc biochemical pathways were identified as having significantly different fold-changes between the two patient groups (P < 0.05, MLRM). Relative abundances diverged in opposite directions in five biochemical pathways: ADP-L-glycero- and beta-D-manno-heptose Biosynthesis (A) and Lipid IVA biosynthesis (C) increased in the MCII+ group, but decreased in the MCII− group; myo-, chiro- and scyllo-inositol Degradation (E), Chorismate Biosynthesis from 3-dehydroquinate (F), and Superpathway of Aromatic Amino Acid Biosynthesis (G) decreased in the MCII+ group, but increased in the MCII− group. P values shown above the box plots were found using multiple linear regression models (MLRMs) designed to test for the statistical significance of the association between MCII patient group and fold-change in relative abundances of microbial taxa/pathways. These models were controlled for the following patient factors: age group, sex, smoking status, duration (days) between baseline and follow-up visits, and use of csDMARDs. ^*, 0.01 ≤ P < 0.05. Taxonomic ranks: c, class; o, order; f, family; g, genus; s, species. MetaCyc pathways: A, ADP-L-glycero- and beta-D-manno-heptose Biosynthesis; B, L-rhamnose degradation I; C, Lipid IVA biosynthesis; D, GDP-mannose Biosynthesis; E, myo-, chiro- and scillo-inositol Degradation; F, Chorismate Biosynthesis from 3-dehydroquinate; G, Superpathway of Aromatic Amino Acid Biosynthesis