Descriptive characteristics of the study samples.

<p>Descriptive characteristics of the study samples.</p

The ADHD microbiome contains significantly increased levels of predicted cyclohexadienyl dehydratase (CDT; KEGG Ortholog K01713; EC:4.2.1.51), responsible for phenylalanine synthesis (Fig B in S1 Appendix).

<p>This analysis is based on functional predictions deriving from 16S profiles of the microbiome, as performed by PICRUSt [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0183509#pone.0183509.ref033" target="_blank">33</a>]. Box plots represent the relative abundance of predicted CDT, with 5–95% percentile whiskers (dots represent outliers). The significance was tested with a non-parametric MWU (* p = 0.038), Bonferroni-corrected for 15 K numbers identified.</p

The strongest differentially abundant microbial taxa for ADHD cases (n = 19) versus healthy controls (n = 77), shown in the graphical Cytoscape visualization [32].

<p>Nodes represent taxa (node size represents average relative abundance, for both experimental groups combined), edges (dashed lines) link the different taxonomic levels. The weighed fold-change (node color) is calculated as the 2log of the ratio of the relative abundance between control and ADHD (0 = no difference between genotypes, 1 = twice as abundant in control, etcetera). In other words: yellow to red indicates an overrepresentation in control, hence an underrepresentation in ADHD, and vice versa for light- to dark blue. The significance (node border width) is expressed as the p-value of a Mann–Whitney <i>U</i> test, uncorrected for multiple comparisons.</p

fMRI results.

<p><b>A</b>. Main effect of reward anticipation, cluster-level corrected at the whole-brain level (pFWE < 0.05). Color bars reflect T-values. <b>B</b>. Diagnosis effects in the anatomical region of interest (ROI) of the ventral striatum. <b>C</b>. Negative correlation of the microbiome function CDT (see <b><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0183509#pone.0183509.g004" target="_blank">Fig 4</a></b>) with reward anticipation responses across the whole-brain (n = 28), intensity threshold at p < 0.001 uncorrected (T = 3.45). The clusters in bilateral ventral striatum (x = -11, y = 11, z = -9, cluster size = 8, p(FWE, cluster) = 0.024; x = 11, y = 6, z = -11, cluster size = 2, p(FWE, cluster) = 0.036) are significant after correcting for multiple comparisons across the search volume (cluster-level pFWE < 0.05, SVC), i.e. the anatomically defined ventral striatum shown in panel B. SVC = small volume correction. * indicates p < 0.05.</p

Microbiome sample, fMRI sample, and their overlap.

<p>Microbiome sample, fMRI sample, and their overlap.</p