Fig. 4: Enhanced microbiome protein metabolism associated with peanut oral immunotherapy failure.

a Difference in module eigenvectors of UMM5, UMM7 and UMM50 AA modules between POIT-outcome groups (n = 129; D+R+ = 33, D+R− = 78, D−R− = 18). Data are presented as mean values ± SEM. Boxplots show the median (center line), 25th and 75th percentiles (box bounds), and whiskers extend to values within 1.5× the interquartile range. Statistical comparisons were performed using the two-sided Wilcoxon rank-sum test. b Fecal AA metabolite composition is distinct between POIT outcome groups at b, baseline (n = 43, R² =  0.08; P  =  0.006), and c end of avoidance (n = 43, R² =  0.07; P  =  0.041). PERMANOVA analyses (two-sided) based on Euclidean distance matrix. d Z-scores of all AA metabolite abundance in nine modules associated with POIT outcomes. e POIT responders have an elevated ptpA gene copy number in their fecal microbiome at the end of avoidance compared to POIT non-responders (P.FDR < 0.05, two-sided linear mixed-effects models adjusted for multiple comparisons). Exact P values are provided in Supplementary Data 15. f ptpA gene copy number positively correlates with Ara h2-specific IgE levels at baseline (n = 57, p = 0.004, R² = 0.37), g end of treatment (n = 39, p = 0.0004, R² = 0.53) and h end of avoidance (n = 35, p = 0.05, R² = 0.32). Two-sided Pearson correlation. i Fecal microbiome from children who did not achieve POIT-induced remission showed a greater capacity to metabolize peanut Ara h 2 protein than those who achieved remission (P = 0.032). Ara h 2 concentrations shown are averages of two independent experiments per sample. Each data point represents one biologically independent participant (remission n = 6, no remission = 12), and comparisons were made using a two-sided Wilcoxon rank-sum test. Boxplots show the median (center line), 25th and 75th percentiles (box bounds), and whiskers extend to values within 1.5× the interquartile range. Statistical comparisons were performed using the two-sided Wilcoxon rank-sum test. The control group refers to the BHI medium supplemented with peanut extract and incubated for 48 h with other samples without the microbiome inoculation. BA: bile acid. AA: amino acid. Source data are provided as a Source Data file.