Fig 1: B. fragilis induces excessive bile acid synthesis and inhibits hepatic bile acid excretion through suppression of FXR signaling to promote ICP.a Hepatic mRNA expression levels of bile acids synthetic and bile excretory genes in mice transplanted with fecal microbiota of ICP and healthy controls (n = 6 per group). P values were determined by two-tailed Student’s t-test. b Hepatic mRNA expression levels of bile acids synthetic and bile excretory genes in control group, B. fragilis group and EE2 group (n = 6 per group). c Hepatic mRNA expression levels of bile acids synthetic and bile excretory genes in each group (n = 6 per group). P values were determined by Welch ANOVA with Games-Howell’s multiple comparisons test for b, c. d IHC staining of hepatic bile acids synthetic and bile excretory proteins of mice colonized with B. fragilis together with GDCA or not. Scale bar: 20 μm. e Hepatic mRNA expression levels of bile acids synthetic and bile excretory genes in mice colonized with B. fragilis together with GW4064 (10 mg/kg/d) or not (n = 6 per group). f Hepatic mRNA expression levels of bile acids synthetic and bile excretory genes in WT mice or FXR−/− mice colonized with B. fragilis or not (n = 6 per group). P values were determined by Welch ANOVA with Games-Howell’s multiple comparisons test for e, f. g, h Correlations between B. fragilis abundance and FGF19 (g) or C4 (h) were determined by Spearman’s rank test. i Schematic mechanisms underlying the role of the B. fragilis-bile acid-FXR axis in regulating ICP. Data are presented as mean ± SEM for a-c, e, f. Source data are provided as a Source Data file.
Fig 2: Altered bile acid profiles in patients with PPSLD. (A) The enterohepatic circulation of bile acids. (B) The functional prediction of bacteria was performed using PICRUSt2 analysis in Cohort-1. Estimated copy numbers of the choloylglycine hydrolase gene encoding BSH. (C–E) Serum bile acid composition in Cohort-1. (C) Unconjugated bile acid, (D) conjugated bile acid, and (E) conjugated-to-unconjugated ratio. (F) Serum FGF19 levels in Cohort-1. (G, H) Hematoxylin and eosin staining of (G) normal and (H) PPSLD livers (scale bar: 100 µm). (I, J) Immunohistochemical staining of hepatic CYP7A1 in (I) normal and (J) PPSLD livers (scale bar: 50 µm). (M–P) Bile acid imaging of TCA (M, N) and TCDCA (O, P) was performed by imaging mass spectrometry in (K, M, O) normal and (L, N, P) PPSLD livers. (Q, R) Enlarged views of PPSLD liver sections. (Q) Hematoxylin and eosin staining and (R) bile acid imaging of TCA. Each dot represents one patient, and the bar indicates the median values. Statistical significance was assessed using the Mann–Whitney U test (panels B–F). ∗p < 0.05; ∗∗p < 0.01; ∗∗∗p < 0.001; ∗∗∗∗p < 0.0001; ns, not significant. BSH, bile salt hydrolase; CA, cholic acid; CDCA, chenodeoxycholic acid; DCA, deoxycholic acid; FGF19, fibroblast growth factor 19; LCA, lithocholic acid; PPSLD, post-pancreatectomy steatotic liver disease; TCA, taurocholic acid; TCDCA, taurochenodeoxycholic acid; TDCA, taurodeoxycholic acid; TLCA, taurolithocholic acid.
Supplier Page from Abcam for Human FGF19 ELISA Kit