Regarding gut microbiota composition and gut microbial genes, these have been investigated both before and after liver transplantation. We find extensive differences in the microbiome in PSC, which is not improved after liver transplantation. Rather, the gut microbiome seems to be more severe altered after liver transplantation compared with healthy people, irrespective of whether a recurrence of the disease has taken place. Overall, this suggests that gut microbiome after liver transplantation could also be a source of driving factors for the disease, and provides a strong rationale for studying PSC and recurrent PSC further in parallel. Furthermore, the findings suggest that gut microbial functions (gut signals) are of importance.
Following the characterisation of the altered gut microbial functions, we found clear signs of reduced potential to produce of certain essential nutrients in the gut bacteria, including some vitamins and amino acids. Importantly, we found that the corresponding levels of these nutrients in blood are reduced in patients with PSC, and low levels associate with poor prognosis. In particular, this was the case for the essential vitamin B6. Deficiency of active vitamin B6 (pyridoxine-5-phoshate, or PLP) was highly prevalent and associated with increased chanced of liver transplantation-free survival. Vitamin B6 therefore seems to be an important biomarker of disease severity. In addition it is a potential treatment target, and as part of this project we have developed and now opened a clinical trial to test the effect of vitamin B6 therapy in PSC.
In addition, we have performed a large scale analysis of >1000 different biochemical substances in blood, some of which are of bacterial origin. Since the liver is a major regulator of the human metabolism, many of the measued biochemicals are altered just because liver disease is present and not because they are important for disease. We have used this project to develop analytical approaches to detect which are really important, and we believe we have detected key microbial factors that could be driving liver disease and thus represent important project in this field.
Although many of these observations are already published, we are still working on some of the findings, thus the project is a rich source of new data on PSC. However, the perhaps most important output is the potential of new biomarkers and therapy, which could influence clinical care within a fairly short timeframe.
