a, Absence of microbiota characterized by higher PA (Swiss-webster female, 2-tailed Mann-Whitney, n=3 germ free,−5 conventional mice, p=0.04). b, Mouse model of humanization. c, Healthy and low PA microbiota causes host fecal PA drop (n=6 feces/phenotype, dots represent average, presented as mean ± s.d). d, Post-humanization PA is dependent on microbiota. Mice with healthy or low PA PI-IBS microbiota have significantly lower PA compared to high PA humanized mice (383 vs. 246 vs. 1,761 BAEE/mg protein, 2-Way ANOVA Tukey’s, n=6 feces/phenotype, dots represent average, *p=0.03 and *p=0.04 respectively). e, Low PA microbiota suppresses host PA. while mice with high PA microbiota have fecal PA similar to GF mice (% of baseline, healthy 24.5 ± 32.8, low PA 17.8 ± 23.9; high PA 116.3 ± 109.7, One-Way ANOVA-Kruskal-Wallis, n=6 feces/phenotype, dots represent average, *p=0.03). f, Humanized mouse pellet frequency. No difference between humanized groups in pellet production. g, Humanized mouse fecal pellet consistency. High PA humanized mice have significantly looser feces. Scored 0=normal to 4=diarrhea. Two averaged independent observations (One-Way ANOVA-Kruskal-Wallis, n=6 feces/phenotype, dots represent average, *p=0.01 for both). h, Pore pathway permeability. Creatinine levels in high PA humanized mice indicate increased pore pathway permeability (for all permeability pathways, n=6 human feces/phenotype; 3 mice/human feces, dots represent averaged mice; high PA PI-IBS 0.81 ± 0.28 mg/dL; low PA PI-IBS 0.58 ± 0.24; healthy 0.51 ± 0.36, One-Way ANOVA-Kruskal-Wallis, *p=0.05). i, Leak pathway permeability. 4-kDa FITC-dextran levels in high PA humanized mice show increased leak pathway permeability (high PA PI-IBS, 19.1 ± 14.6 mg/dL; low PA PI-IBS 23.9 ± 23.9; healthy 13.7 ± 30.3, One-Way ANOVA-Kruskal-Wallis, *p=0.04). j, Unrestricted pathway permeability. No difference in serum rhodamine levels across humanization states. Boxplots as previously described.