PT - JOURNAL ARTICLE AU - Adrian Tett AU - Kun D. Huang AU - Francesco Asnicar AU - Hannah Fehlner-Peach AU - Edoardo Pasolli AU - Nicolai Karcher AU - Federica Armanini AU - Paolo Manghi AU - Kevin Bonham AU - Moreno Zolfo AU - Francesca De Filippis AU - Cara Magnabosco AU - Richard Bonneau AU - John Lusingu AU - John Amuasi AU - Karl Reinhard AU - Thomas Rattei AU - Fredrik Boulund AU - Lars Engstrand AU - Albert Zink AU - Maria Carmen Collado AU - Dan R. Littman AU - Daniel Eibach AU - Danilo Ercolini AU - Omar Rota-Stabelli AU - Curtis Huttenhower AU - Frank Maixner AU - Nicola Segata TI - The <em>Prevotella copri</em> complex comprises four distinct clades that are underrepresented in Westernised populations AID - 10.1101/600593 DP - 2019 Jan 01 TA - bioRxiv PG - 600593 4099 - http://biorxiv.org/content/early/2019/04/09/600593.short 4100 - http://biorxiv.org/content/early/2019/04/09/600593.full AB - Prevotella copri is a common inhabitant of the human gut. Interest in P. copri has gathered pace due to conflicting reports on whether it is beneficial or detrimental to health. In a cross-continent meta-analysis exploiting &gt;6,500 available metagenomes supported by new isolate sequencing and recovery of high-quality genomes from metagenomes, we obtained &gt;1,000 P. copri genomes. This 100-fold increase over existing isolate genomes allowed the genetic and global population structure of P. copri to be explored at an unprecedented depth. We demonstrate P. copri is not a monotypic species, but encompasses four distinct clades (&gt;10% inter-clade vs. &lt;4% intra-clade average single nucleotide variants) for which we propose the name P. copri complex, comprising clades A, B, C and D. We show the complex is near ubiquitous in non-Westernised populations (95.4% versus 29.6% in Westernised populations), where all four clades are typically co-present within an individual (61.6% of the cases), in contrast to Westernised populations (4.6%). Genomic analysis of the complex reveals substantial and complementary functional diversity, including the potential for utilisation of complex carbohydrates, suggestive that multi-generational dietary modifications may be a driver for the reduced P. copri prevalence in Westernised populations. Analysis of ancient stool microbiomes highlights a similar pattern of P. copri presence consistent with modern non-Westernised populations, allowing us to estimate the time of clade delineation to pre-date human migratory waves out of Africa. Our analysis reveals P. copri to be far more diverse than previously appreciated and this diversity appears to be underrepresented in Western-lifestyle populations.