Fig. 5. Host–microbiome interactions at prodromal and early α-synucleinopathy.

a The associations between taxa abundance and host factors were assessed by using MaAsLin 2. Only significant results were shown in the heatmap (Benjamini–Hochberg adjusted P values <0.25). For detailed descriptions and results of MaAsLin 2, see Supplementary Dataset 10. b Interactions of overall microbial composition and host factors. Boxplot displayed the inter-individual variation explained by each host factor in whole samples by using PERMANOVA test (i.e., PERMANOVA R², permutations = 99,999). “***”, “**”, and “*” represented Benjamini–Hochberg adjusted P values <0.001, <0.01, and <0.05, respectively. Heatmap showed the stage-specific (i.e., each stage versus control) impact of host factors. All significant associations were highlighted with red color (q value <0.05 from the PERMANOVA model). See also Supplementary Dataset 4. c MaAsLin 2 test revealed significant correlations between BMF score and short-chain fatty acids-producing bacteria Butyricicoccus, as well as the co-occurrence of antidepressant use and RBD/early PD-enriched genera Akkermansia. Beta and P value (without Benjamini–Hochberg adjustment) were derived from MaAsLin 2 (two-sided test, see also Supplementary Dataset 10). The thick line in box represents the median values, while the lower and upper boundaries represent the first and third quartiles, respectively; whiskers extend up to values within 1.5 times of the interquartile range; outliers are plotted as individual points beyond the whiskers. RBD REM sleep behavior disorder, RBD-FDR first-degree relatives of patients with RBD, PD Parkinson’s disease, PERMANOVA permutational multivariate analysis of variance, BMF bowel movement frequency, PPIs proton pump inhibitors, CLR centered log ratio, MaAsLin 2 Microbiome multivariable associations with linear model, ns not significant, na not applicable. Source data are provided as a Source Data file.