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. 2020 Jul 16;106(8):2131–2146. doi: 10.3324/haematol.2019.242990

Figure 3.

Figure 3.

Bile acid treatment improves acute graft-versus-host disease outcome in mice. (A) Transplantation model with BALB/c (H-2kd) as donor and C57BL/6 (H- 2kb) as recipient. Recipient animals were treated with 200 mg/kg body weight tauroursodeoxycholic acid (TUDCA) or an equal volume of vehicle from day 0 until day 10 after bone marrow transplantation (BMT) by a daily intraperitoneal injection. (B) Survival of C57BL/6 mice transplanted as shown in (A). Numbers (N) represent individual mice, the P-value was calculated using the two-sided Mantel-Cox test. (C) Transplantation model with C57BL/6 (H-2kb) as donor and BALB/c (H-2kd) as recipient. Recipient animals were treated with 200 mg/kg body weight TUDCA or an equal volume of vehicle from day 0 until day 10 after BMT by a daily intraperitoneal injection. (D) Survival of BALB/c mice transplanted as described in (C). Data were pooled from three independent experiments, numbers (N) represent individual mice. The P-value was calculated using the two-sided Mantel-Cox test. (E) Graft-versus-host disease (GvHD) histopathology scores of liver, small intestine and colon assessed on day 7 after BMT (C57BL/6 in BALB/c model). Data were pooled from two independent experiments, numbers (N) represent individual mice. P-values were calculated using the ordinary one-way ANOVA test with correction for multiple comparisons. (F) Serum cytokine concentrations in untreated mice and transplanted mice determined on day 14 after BMT (C57BL/6 in BALB/c model). Numbers (N) represent individual mice. P-values were calculated using the ordinary one-way ANOVA test with correction for multiple comparisons. (G and I) Fecal samples were collected for microbial analysis on day 5 after BMT. Numbers (N) represent individual mice. Data were pooled from two independent experiments. P-values were calculated using the ordinary one-way ANOVA test with correction for multiple comparisons; ns: not significant. (G) The Shannon index as a surrogate parameter for microbial diversity. (H) The reversed Simpson index as a surrogate parameter for microbial diversity. (I) Relative abundance of specified bacterial genera. (J) C57BL/6 mice were treated with an antibiotic cocktail comprising 1 mg/mL cefoxitin, metronidazole, neomycin and gentamycin for 2 weeks before they underwent BMT as described in (A). (K) Survival of C57BL/6 mice transplanted and treated as described in (J). Numbers (N) represent individual mice. Data were pooled from two independent experiments. Statistical analysis was performed using the two-sided Mantel-Cox test.