Figure 4.
GVHD and antibiotic treatment promote gastrointestinal dysbiosis. (A) The Bray-Curtis metric test shows the dissimilarity of the microbiome β diversity between the 3 groups (untreated, vehicle-treated, and teduglutide-treated mice). Stool samples from colon were isolated on day 5 after allo-HCT from BALB/c mice. Mice were treated with teduglutide or vehicle from day −3 until day +3 unless differently specified. Representative data from 2 independent experiments. (B-C) Relative abundance of specific bacteria at the genus level. Increased Firmicutes bacterial load has been associated with GVHD. We observed an upregulation of Flintibacter bacteria (belonging to the Firmicutes phylum) in the BALB/c allo-HCT vehicle-treated group (n = 6), and those decline after teduglutide treatment (n = 6). On the other hand, the loss of unclassified Bacteroidales due to GVHD was compensated by the treatment with teduglutide (n = 6 per group). Representative data from 2 independent experiments. The P values were calculated using a 2-sided Mann-Whitney U test. (D) Percentage survival of C57BL/6 mice undergoing allo-HCT treated with teduglutide from day −3 to day 3 + broad spectrum antibiotics or normal water (vehicle) from day −14 to day −1 (n = 10 per group). Data are derived from 2 independent experiments. P value was calculated using the Mantel-Cox test. (E) Gene expression of interferon-related genes in the intestinal tract of BALB/c mice treated from day −3 until day 10 with teduglutide compared with mice treated with vehicle. *Nonadjusted value of P < .05. The experiment was performed once.