作者
Malte Rühlemann,Shauni Doms,Corinna Bang,Shauni Doms,Lucas Moitinho‐Silva,Louise B. Thingholm,Fabian Frost,Frauke Degenhardt,Michael Wittig,Jan Christian Kässens,Frank Ulrich Weiß,Annette Peters,Klaus Neuhaus,Uwe Völker,Henry Völzke,Georg Homuth,Stefan Weiß,Harald Grallert,Matthias Laudes,Wolfgang Lieb,Dirk Haller,Markus M. Lerch,John F. Baines,André Franke
摘要
The intestinal microbiome is implicated as an important modulating factor in multiple inflammatory1,2, neurologic3 and neoplastic diseases4. Recent genome-wide association studies yielded inconsistent, underpowered and rarely replicated results such that the role of human host genetics as a contributing factor to microbiome assembly and structure remains uncertain5-11. Nevertheless, twin studies clearly suggest host genetics as a driver of microbiome composition11. In a genome-wide association analysis of 8,956 German individuals, we identified 38 genetic loci to be associated with single bacteria and overall microbiome composition. Further analyses confirm the identified associations of ABO histo-blood groups and FUT2 secretor status with Bacteroides and Faecalibacterium spp. Mendelian randomization analysis suggests causative and protective effects of gut microbes, with clade-specific effects on inflammatory bowel disease. This holistic investigative approach of the host, its genetics and its associated microbial communities as a 'metaorganism' broaden our understanding of disease etiology, and emphasize the potential for implementing microbiota in disease treatment and management.