Fig. 1: Increased urdA enzyme abundance in the gut microbiome of patients with Parkinson’s disease (PD) and PD key pathologies induced by gut-colonization of imidazole propionate (ImP)-producing Streptococcus mutans (S. mutans).
From: Gut microbial production of imidazole propionate drives Parkinson’s pathologies
a Relative abundance of S. mutans in the gut microbiome of patients with PD (n = 491) and age-matched healthy controls (n = 234). Data were log10-transformed and are presented as box plots showing minimum, 25% quartile, median, 75% quartile, and maximum. b, c Normalized gene copy numbers of urocanate reductase (urdA, b) and histidine ammonia lyase (hutH, c) in the gut microbiome from patients with PD and age-matched healthy controls. Box plots represent the median (centre line), 25%–75% quartile (bounds of box), minima and maxima (whiskers), with all individual data points shown. d Schematic illustration of the experimental procedure showing colonization of germ-free (GF) mice with S. mutans or pasteurized S. mutans (P-S. mutans) via oral gavage. Fecal samples were collected from GF mice before (D0) and 28 days after S. mutans colonization. Created in BioRender. Kim, J. (https://BioRender.com/xsj2j6c). e Quantification of live S. mutans in the feces by assessing viable colony formation from GF mice gavaged with vehicle (Veh), S. mutans, or P-S. mutans (n = 7 mice per Veh and P-S. mutans group, n = 8 mice per S. mutans group). CFU, colony forming unit. f (Left panel) Representative anti-TH (tyrosine hydroxylase) immunohistochemistry images of ventral midbrains from GF mice colonized with S. mutans or P-S. mutans, or vehicle control. Brain sections were counterstained with Nissl. Magnified images showing dopaminergic processes in the substantia nigra pars reticulata (SNr) are also presented below. (Right panel) Stereological counts of TH-positive and Nissl-stained dopaminergic neurons in the substantia nigra pars compacta (SNpc). Relative TH fiber density and Nissl-stained neuronal counts in the SNr (n = 7 mice per group). Scale bar = 100 μm, and 25 μm for enlarged images, respectively. g (Left panel) Representative images of inflammatory astrogliosis in ventral midbrains of GF mice colonized with S. mutans, P-S. mutans, or vehicle control, assessed via GFAP immunohistochemistry. Magnified images of the SNpc were presented on the right. (Right panel) Quantification of GFAP-positive area as percentage of total area (% area fraction) (n = 7 mice per group). Scale bar = 100 μm. h (Left panel) Representative images of inflammatory microgliosis in ventral midbrains of GF mice colonized with S. mutans, P-S. mutans, or vehicle control, assessed via Iba1 immunohistochemistry. Magnified images of the SNpc subregions on the right highlight inflammatory microgliosis. (Right panel) Quantification of Iba1-positive area fraction (%; n = 3 mice per group) and microglial soma size, measured from 10 cells per mouse (n = 3 mice per group). Scale bar = 100 μm. i Assessment of bradykinesia in GF mice colonized with S. mutans or P-S. mutans monitored by measuring latency to reach the base in the pole test (n = 7 mice per Veh and P-S. mutans group, n = 8 mice per S. mutans group). j Quantification of ImP concentration in the plasma from GF mice gavaged with Veh, S. mutans, or P-S. mutans. (n = 7 mice per Veh and P-S. mutans group, n = 8 mice per S. mutans group). k Quantification of ImP concentration in the brains from GF mice gavaged with Veh, S. mutans, or P-S. mutans. (n = 4 mice per Veh and P-S. mutans group, n = 6 mice per S. mutans group). Quantitative data are expressed as the mean ± standard error of the mean (S.E.M). **P < 0.01, ***P < 0.001; ns, not significant. P values were determined by the two-sided Wilcoxon rank-sum test (a-c), two-way ANOVA with Tukey’s post hoc test (e), and one-way ANOVA with Tukey’s post hoc test (f–k). Source data and test statistics are provided as a Source Data file. See also Supplementary Fig. 1.
