Figure 1.
DMF treatment specifically recomposes the gut microbiota. (a) In this prospective observational study, serum metabolome, gastrointestinal microbiota as well as clinical and paraclinical parameters were assessed in 20 individuals during the first year of oral DMF treatment to delineate markers of clinical outcomes. (b) Random Forest analysis of longitudinal changes within all 805 identified serum metabolites. Higher mean decrease accuracy suggest more relevant longitudinal changes (top 30 metabolites shown), citrate cycle metabolites are marked in purple. (c) Glycolysis and citrate cycle metabolites, as measured by mass spectrometry, compared between baseline and 3 months timepoints. (d) Non-metric multidimensional representation (NMDS) of the gastrointestinal microbiota composition of baseline (blue) and 3 months (purple) samples (stress: 0.17). Circles represent confidence interval of 95%. (e) Volcano plot of 3 months/baseline microbial species, significantly (padj<0.05) overrepresented species at baseline (left) or 3 months (right) illustrated in red. (f) Box plots of log10-transformed normalized relative abundances of the four most affected (according to volcano plot, 1E) microbial species at baseline (blue) and 3 months (purple). (g) Venn diagram from AMON analysis for baseline vs. 3 months for metabolic pathways of the gastrointestinal microbiota. (h) Visualization of AMON analysis of putative origin of metabolites (circles) and enzymatic reactions (rectangles) of the citrate cycle, with dark blue indicating exclusive bacterial origin, yellow indicating exclusive human origin, and orange indicating compounds detected in serum. Green color labels compounds of either human or bacterial origin without certain attribution.