Background: After liver transplantation (LT) for Primary Sclerosing Cholangitis (PSC), patients have a risk of up to 27% at recurrence of their liver disease (rPSC) with a negative impact on survival. The pathogenesis of both PSC and rPSC are largely unknown, but the idea of a multifactorial concept is broadly accepted. The gut microbiome is suggested to be one of these factors, by either altering the immune system and/or affecting the bile acid-gut microbiome axis. Coexisting Inflammatory Bowel Disease (IBD) in numerous patients with PSC emphasizes this theory. We have investigated whether the gut microbiome differs at time of transplant between patients with and without rPSC.
Materials and Methods: All patients who receive a LT at our center undergo a screening colonoscopy with biopsies. These biopsies, stored in FFPE, were used to extract bacterial DNA using the RTP Bacteria DNA Mini Kit (Stratec®). This DNA was used for 16S rRNA gene sequencing, revealing the microbiome of each patient. Using shrinkage-based variable selection we identified bacteria associated with rPSC. Recurrence PSC was defined according to the Mayo criteria, excluding secondary causes of post-LT biliary disease.
Results and Discussion: A total of 100 FFPE samples were available from patients who received a LT between 1987 and 2015 for PSC. Median time between colon sampling and LT was 7.2 months (range 1.7-32.8). The recurrence rate in this cohort was 14% (n=14) after a median of 5.0 years (range 0.5-10.1). We identified two bacteria (genus level) from different phyla that were significantly more abundant in the rPSC group: Microbacterium (phylum Actinobacteria) and Thermicanus (phylum Firmicutes). Log odds ratios were 174 and 55, respectively.
Conclusion: Despite similar disease pre-LT, we found that two genera, the Microbacterium and Thermicanus, were significantly more abundant in the pre-LT colon of patients who developed rPSC post-LT as compared to those who did not. This difference in the colon microbiome may contribute to the pathogenesis of rPSC, and might help to understand the link between IBD and rPSC.