Fecal microbiota of pRD patients and Rag1 ^w/w mice is characterized by a severe restriction of microbial diversity with specific microbial signatures. (A) Alpha diversity in human fecal microbiota from healthy donors (HD, n = 23) and patients with pRD (n = 15). Significance was determined by a Kruskal–Wallis chi-squared test. (B–D) Relative abundance of oral bacteria (B), Ruminococcaceae (C), and Butyricicoccus and Coprococcus (D) in human fecal microbiota from HD (n = 23) and patients with pRD (n = 15). Significance was determined by a Kruskal–Wallis chi-squared test. (E) Principal Coordinates Analysis (PCoA) using the Euclidean distance of the IgA scores of human fecal microbiota from HD, patients with pRD, and patients with pRD and IBD. (F) IgA scores of Coprococcus, Butyricicoccus, and Faecalibacterium from human fecal microbiota of HD and pRD patients. Significance was determined by a Kruskal–Wallis chi-squared test. (G) Alpha diversity of fecal microbiota from littermate wild-type (+/+, n = 4) or Rag1^w/w (W/W, n = 11) mice kept in co-housing conditions and profiled at 12 wk of age by 16S rRNA gene sequencing. Significance was determined by a Kruskal–Wallis chi-squared test. (H) Time course analysis of Shannon index alpha diversity of fecal microbiota from littermate +/+ or W/W mice collected from isolated mice at 3, 5, 10, and 14 wk of age (n = 5/group). (I) Relative abundance of Ruminococcaceae in the fecal microbiota of +/+ or W/W mice collected from isolated mice at 3, 5, 10, and 14 wk of age (n =5/group). Significance in H and I was determined by the linear mixed-effects model Shannon ∼Genotype + AgeInWeeks + (1|SubjectID) with the lmerTest R package. (J) PCoA using the Euclidean distance of the IgA scores of murine fecal microbiota from +/+ (n = 8) and W/W mice (n = 7). (K) IgA scores of Ruminococcaceae from fecal microbiota from +/+ (n = 8) and W/W (n = 7) mice. Significance was determined by a Kruskal–Wallis chi-squared test. (L) Median relative abundance of taxa contributing to PICRUSt-inferred pathways whose abundance is significantly (FDR < 0.05) different between W/W and +/+ mice fecal microbiota (n = 5/group). (M) Parallel univariate analysis comparing the fecal metabolome of W/W mice to +/+ mice (n = 5/group) with notable metabolite families highlighted by color. FDR levels as calculated via a Benjamini–Hochberg correction are indicated. Data are from at least two independent experiments. *P < 0.05, **P < 0.01, ****P < 0.0001. HD, healthy donors.