Individuals with PSC had fewer genes involved in synthesis of B vitamins and branched chain amino acids (BCAAs), and lower serum levels of vitamin B6 and BCAAs, which were associated with worse liver transplant-free survival, Dr. Johannes R. Hov of the Norwegian PSC Research Center at Oslo University Hospital Rikshospitalet and colleagues found.
Previous cross-sectional studies found differences in the composition of the fecal bacterial microbiome in PSC patients compared with healthy individuals, Dr. Hov and his team note.
"Overall, both human and experimental evidence suggest that gut microbes may act as disease modifiers in PSC," they write in Gastroenterology. "The mechanisms underlying these effects are so far not known, but current data suggest that altered bile acid homeostasis, increased bacterial translocation or uncharacterized immune alterations could be relevant."
The authors performed full shotgun metagenomic sequencing in two cohorts of PSC patients to better characterize microbial species linked to PSC and identify any changes in microbial function. One cohort, from Norway, included 69 PSC patients and 38 healthy controls, and another, from Germany, consisted of 67 PSC patients and 120 healthy controls.
The overall analysis included fecal DNA from 136 PSC patients, 58% of whom had inflammatory bowel disease (IBD); 158 HCs; and 93 patients with IBD but no PSC.
Overall, PSC patients had significantly fewer microbial genes than HCs. The PSC group had an increased prevalence of Clostridium species and depletion of several other species, including Eubacterium spp and Ruminococcus obeum. There were nine species with a higher prevalence and five species with a lower prevalence in PSC compared to HCs.
Out of 121 metabolic pathways identified including 424 enzyme families, there were 53 pathways and 106 families differentially abundant in PSC compared to HC.
Metabolic pathways associated with isoleucine synthesis and enzyme families associated with isoleucine, valine and leucine were depleted in PSC compared to HCs. Patients with IBD showed a similar pattern to PSC. Metabolic pathways associated with B vitamin synthesis were also differentially abundant in PSC.
The authors also looked at vitamin B and BCAA metabolites in plasma from a separate cohort of 191 PSC patients and 48 HCs. The PSC patients had reduced levels of PLP, the main active form of vitamin B6, and lower levels of isoleucine, leucine and valine. PLP patients who reached one of the study's endpoints (liver transplantation or death) had lower concentrations of PLP and BCAAs.
The microbiome in PSC patients was similar whether or not they also had IBD.
"Taken together, identification of altered bacterial functions pointed us to important biology that was altered also systemically. It should be emphasized that we do not show a direct link between the gut and blood, but further studies should investigate such a link and whether PLP represents a mechanism or only a marker of disease activity and severity in PSC," Dr. Hov and colleagues conclude.
Dr. Hov was not available for an interview by press time.
SOURCE: https://bit.ly/38hjydK Gastroenterology, online December 30, 2020.
By Reuters Staff
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