Figure 6.

Colonization of the liver by circulating intestinal microbes impairs liver regeneration

(A) SPF Rorc(γt)^−/+ and Rorc(γt)^−/− littermate mice were subjected to sham or PH. Immediately after the operation, 10⁷ CFU of E. coli JM83 were injected i.v. and E. coli titers (CFU; geometric mean ± SD) were assessed in the blood.

(B) E. coli titers (CFU) were assessed in the blood 5 min after PH.

(C) Experimental scheme: SPF wild-type mice were i.v. injected with 10⁷ CFU E. coli JM83 6 and 2 days prior to and 12 h after PH (in D and E).

(D–H) Hepatic regeneration 48 h after surgery was assessed by analyzing the percentage of Ki-67⁺ hepatocytes or the expression of cell cycle regulatory genes (Foxm1b and Ccna2). Representative images are presented on the right and quantification of proliferation is presented on the left. (F–H) SPF wild-type, Rag1^−/−, and Rag2^−/−Il2rg^−/− mice underwent PH. (H) Correlation of hepatic bacterial load and liver regeneration in SPF Rag2^−/−Il2rg^−/− mice. Scale bars in the pictures indicate 100 μm. Geometric means for log scales and arithmetic means for linear scales are shown. Data in (A) and (B) are representative of n = 3–7 mice per group in two independent experiments, and data in (D)–(H) are pooled based on n = 6–14 mice from two or more independent experiments. The p values are indicated as follows: ^∗p ≤ 0.05, ^∗∗p ≤ 0.01, ^∗∗∗p ≤ 0.001, and ^∗∗∗∗p ≤ 0.0001.