Biliary microbial patterns in primary sclerosing cholangitis are linked to poorer transplant-free survival

Abstract

Background: Factors that determine individual disease course of patients with primary sclerosing cholangitis (PSC) are poorly understood. Although an association between gut microbes and disease outcome has been suggested, little is known about the role of microbes in the biliary tract.

Methods: We analyzed microbial cultures from bile specimens obtained during routine endoscopic retrograde cholangiopancreatography (ERCP) and intraoperatively before liver transplantation in 114 patients with PSC in our tertiary academic center. The presence of bacterial and fungal species was correlated with clinical characteristics and outcome data.

Results: A total of 87 patients (76%) had positive bile culture results. The presence of concomitant inflammatory bowel disease (IBD) was associated with positive bile culture results in multivariate analysis (OR, 4.707; 95% CI, 1.688-13.128; p=0.003). Enterococcus spp. in the bile was associated with a more frequent occurrence of liver transplantation and/or death (OR, 2.778; 95% CI, 1.147-6.728; p=0.021) and recurrent (≥3) cholangitis episodes (OR, 2.839; 95% CI, 1.037-7.768; p=0.037). Biliary candidiasis was linked to a higher frequency of recurrent (≥3) cholangitis episodes (OR, 5.677; 95% CI, 1.940-16.616; p=0.001). Proton pump inhibitor intake conferred a clinical feature associated with biliary candidiasis in multivariate analysis (OR, 3.559; 95% CI, 1.275-9.937; p=0.016).

Conclusions: Our data indicate that in patients with PSC, presence of Enterococcus spp. and Candida spp. in bile is associated with an adverse outcome. Concomitant IBD is linked to presence of microbes in bile, and proton pump inhibitor intake is a feature associated with biliary candidiasis in patients with PSC.

FIGURE 1

Flowchart with overview of outcome parameters of the total cohort and subcohorts. The p-values are based on the Pearson χ² test. Significant results (p < 0.05) are underlined and shown in bold type. Abbreviation: spp., species.

FIGURE 2

Flowchart with overview of outcome parameters of particular pathobionts. The p-values are based on the Pearson χ² test. Significant results (p < 0.05) are underlined and shown in bold type. Abbreviation: spp., species.

FIGURE 3

Presence of Enterococcus spp. is associated with poorer transplant-free survival and recurrent cholangitis episodes. (A) and (B) demonstrate the link between presence of Enterococcus spp. in bile and occurrence of liver transplant and/or liver-related death (OR, 2.778; 95% CI, 1.147–6.728; p = 0.021) (A) and recurrent cholangitis episodes (≥3) (OR, 2.839; 95% CI, 1.037–7.768; p = 0.037) (B). No significant correlation was found between biliary candidiasis and liver transplant and/or liver-related death (OR, 2.195; 95% CI, 0.804–5.996; p = 0.119) (C). There was a strong correlation between biliary candidiasis and recurrent cholangitis episodes (≥3) (OR, 5.677; 95% CI, 1.940–16.616; p < 0.001) (D). A p-value < 0.05 was considered significant. Abbreviation: spp., species.

FIGURE 4

Presence of IBD is associated with positive bile culture results, and PPI intake is linked to biliary candidiasis. Presence of IBD is significantly associated with presence of microbes in bile (OR, 3.560; 95% CI, 1.424–8.896; p = 0.005) (A). PPI intake was significantly associated with biliary candidiasis (OR, 4.111; 95% CI, 1.540–10.973; p = 0.003) (B). A p-value < 0.05 was considered significant. Abbreviations: IBD, inflammatory bowel disease; PPI, Proton pump inhibitor; spp., species.