原发性硬化性胆管炎中功能微生物组学的变化 | 热心肠日报
Altered gut microbial metabolism of essential nutrients in primary sclerosing cholangitis
原发性硬化性胆管炎中肠道微生物必需营养代谢的变化
10.1053/j.gastro.2020.12.058
2020-12-30, Article
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Background and Aims: To influence host and disease phenotype, compositional microbiome changes, which have been demonstrated in patients with primary sclerosing cholangitis (PSC), must be accompanied by functional changes. We therefore aimed to characterize the genetic potential of the gut microbiome in PSC compared to healthy controls (HCs) and inflammatory bowel disease (IBD).
Methods: Fecal DNA from two cohorts (one Norwegian and one German), in total comprising 136 patients with PSC (58% with IBD), 158 HCs and 93 IBD patients without PSC were subjected to metagenomic shotgun sequencing, generating 17 billion paired end sequences, which were processed using HUMAnN2 and MetaPhlAn2, and analyzed using generalized linear models and random effects meta-analyses.
Results: PSC patients had fewer microbial genes compared to HC (P<.0001). Compared to HC, PSC patients showed enrichment and increased prevalence of Clostridium species, and a depletion of e.g., Eubacterium spp. and Ruminococcus obeum. Patients with PSC showed marked differences in the abundance of genes related to vitamin B6 synthesis and branched chain amino acid (BCAA) synthesis (Qfdr<.05). Targeted metabolomics of plasma from an independent set of PSC patients and controls found reduced concentrations of vitamin B6 and BCAAs in PSC (P<.0001), which strongly associated with reduced liver transplantation-free survival (log-rank P<.001). No taxonomic or functional differences were detected between PSC patients with and without IBD.
Conclusion: The gut microbiome of PSC patients exhibits large functional differences compared to HC, including microbial metabolism of essential nutrients. Alterations in related circulating metabolites associated with disease course, suggesting that microbial functions may be relevant for the disease process in PSC.
First Authors:
Martin Kummen,Louise B Thingholm
Correspondence Authors:
Andre Franke,Johannes R Hov
All Authors:
Martin Kummen,Louise B Thingholm,Malte C Rühlemann,Kristian Holm,Simen H Hansen,Lucas Moitinho-Silva,Timur Liwinski,Roman Zenouzi,Christopher Storm-Larsen,Øyvind Midttun,Adrian McCann,Per M Ueland,Marte L Høivik,Mette Vesterhus,Marius Trøseid,Matthias Laudes,Wolfgang Lieb,Tom H Karlsen,Corinna Bang,Christoph Schramm,Andre Franke,Johannes R Hov