Fig. 4: Iron supplementation rescues the impact of entacapone on the gut microbiome.
From: The Parkinson’s disease drug entacapone disrupts gut microbiome homeostasis via iron sequestration
a, Siderophore detection assay showing the change in colour in the presence of 0.1 mM entacapone. The indicator complex changed back to its original colour (blue) after addition of excess ferric iron. b, Growth of B. thetaiotaomicron in the absence of drug or in the presence of: ENT-Hi; ENT-Hi preloaded with FeSO4 (ENT-Hi: Fe(III)), ENT-Hi preloaded with FeCl3 (ENT-Hi: Fe(III)); or ENT-Hi supplemented with Fe(III) (FeSO4) or Cu(II) (CuCl2). No drug and ENT-Hi conditions: n = 6; all other conditions: n = 3 independent growths per condition. Data represent the mean ± s.e.m. The box plots in the middle and right refer to the same data as displayed on the left plot but split by incubation time. c. Total cell loads in faecal samples (mix from 5 donors) incubated with either ENT-Hi, FeSO4 (No drug + 1.0 mM Fe), both (ENT-Hi + 1.0 mM Fe), or ENT-Hi pre-incubated with FeSO4 (ENT-Hi:Fe) in sM9 medium. In b and c, Fe(II) is oxidized to Fe(III), and thus Fe(III) is present. Data represent the mean ± s.e.m. of 3 incubation vials per condition (Supplementary Table 13). d, Relative (left) and absolute (right) genus abundance profiles of microbial communities incubated as described in c and assessed by 16S rRNA gene amplicon sequencing (Supplementary Tables 14 and 15). All genera present at relative abundances below 0.01 or absolute abundances below 1.5 × 106 cells per ml were assigned to the category ‘Other’. Data are from triplicates per condition. e, Alpha diversity metrics in gut microbial communities at 24 h of incubation. f, Bubble plot denoting the fold change (log2FC) in absolute abundance relative to control incubations for the 25 most abundant ASVs. P values (Wald test) were adjusted using the Benjamini–Hochberg method. In b and e, boxes represent the median, first and third quartiles. Whiskers extend to the highest and lowest values that are within 1.5× the interquartile range. In b, c and e: *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001; unpaired two-sided t-test with ‘No drug’ used as the reference group. Only statistically significant differences are indicated.
