Fig. 5: Microbial gene-families and pathways with functional relevance to PD.
From: Metagenomics of Parkinson’s disease implicates the gut microbiome in multiple disease mechanisms
Analysis included N = 724 biologically independent samples from 490 PD and 234 neurologically healthy control (NHC) subjects. Overall, 15% of microbial gene-families (KO groups) and 30% of pathways (MetaCyc) tested were elevated or depleted in PD, a conservative estimate derived from consensus at FDR < 0.05 by two statistical methods (MaAsLin2 and ANCOM-BC) (Supplementary Data 9, 10). Examples are shown here, grouped by inferred functional relevance to PD (left panel). Data show increased levels of microbial activities that could contribute to PD pathogenesis (immunogenicity, alpha-synuclein aggregation, and creation of toxic metabolites), and reduced levels of protective mechanisms (anti-inflammation, and neuroactive and neuroprotective molecules). a Relative abundances (used in MaAsLin2). b Bias-corrected observed abundances (used in ANCOM-BC). c Fold change in PD vs. NHC as estimated by MaAsLin2 and ANCOM-BC. Y-axis: KO groups (identifiers begin with “K”, gene symbol in parentheses) and pathways (“PWY”). X-axis: Log2 transformed relative abundances (used in MaAsLin2) (a), or natural log transformed bias-corrected observed abundances (used in ANCOM-BC) (b), with untransformed relative abundances in parenthesis for easier interpretation; (c) fold change in differential abundance in PD vs. NHC (squares and circles) with 95% confidence interval (CI; solid and dashed lines), calculated from beta and standard errors estimated by MaAsLin2 and ANCOM-BC. Content in (a and b): Boxplots show frequency distribution of each KO and pathway in PD (blue green) and NHC (orange) metagenomes. Left, middle, and right vertical boundaries of each box represent first, second (median), and third quartiles of the data. The absence of a box indicates >75% of samples had zero abundance. The lines extending from the two ends of each box represent 1.5x outside the interquartile range (range=(abundance value at 75% minus abundance value at 25%)x1.5). Points beyond the lines are outlier samples. Content in (c): Fold change difference between PD and NHC in log2-transformed relative abundance (square with solid line of 95% CI, MaAsLin2), or natural log transformed bias-corrected observed abundances (circle with dotted line of 95% CI, ANCOM-BC). Blue: elevated in PD, red: reduced in PD. LPS: Lipopolysaccharide. LTA: Lipoteichoic acid. BLP: murein/bacterial lipoprotein. SCFA: short-chain fatty-acid. TMA: Trimethylamine.
