Resolution of systemic inflammatory signatures and improvement of fecal microbiota composition after BMT, and persistence of colonic inflammation after ustekinumab in pRD patients. (A) Scatter plots (mean with SD) showing serum cytokine levels in HD (n = 29) and patients with pRD (n = 7) before and after BMT. Red triangles indicate pRD subjects with IBD. Statistical analysis was performed using a Kruskal–Wallis test to compare HD with pRD before and after BMT (*P < 0.05, ****P < 0.0001), while a paired Wilcoxon test was used to compare pRD before and after BMT (#P < 0.05). (B) Alpha diversity in human fecal microbiota from HD (n = 23) and patients with pRD before and after BMT (n = 2). (C and D) Relative abundance of oral bacteria (C) and of Ruminococcaceae (D) in human fecal microbiota from HD (n = 23) and patients with pRD before and after BMT (n = 2). (E) Immunohistochemical analysis of colon biopsy isolated from one pRD patient (P3) before and after treatment with ustekinumab, showing H&E and CD3 staining, as well as RNAscope analysis for the expression of CXCL9 transcript. All images are 10× magnification (scale bar for H&E pretreatments is 200 μm; other scale bars are 100 μm). HD, healthy donors.
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