title: Interpreting Prevotella and Bacteroides as biomarkers of diet and lifestyle.
abstract: BACKGROUND
  In a series of studies of the gut microbiome, "enterotypes" have been used to classify gut microbiome samples that cluster together in ordination analyses. Initially, three distinct enterotypes were described, although later studies reduced this to two clusters, one dominated by Bacteroides or Clostridiales species found more commonly in Western (American and Western European) subjects and the other dominated by Prevotella more often associated with non-Western subjects. The two taxa, Bacteroides and Prevotella, have been presumed to represent consistent underlying microbial communities, but no one has demonstrated the presence of additional microbial taxa across studies that can define these communities.
  
  
  RESULTS
  We analyzed the combined microbiome data from five previous studies with samples across five continents. We clearly demonstrate that there are no consistent bacterial taxa associated with either Bacteroides- or Prevotella-dominated communities across the studies. By increasing the number and diversity of samples, we found gradients of both Bacteroides and Prevotella and a lack of the distinct clusters in the principal coordinate plots originally proposed in the "enterotypes" hypothesis. The apparent segregation of the samples seen in many ordination plots is due to the differences in the samples' Prevotella and Bacteroides abundances and does not represent consistent microbial communities within the "enterotypes" and is not associated with other taxa across studies. The projections we see are consistent with a continuum of values created from a simple mixture of Bacteroides and Prevotella; these two biomarkers are significantly correlated to the projection axes. We suggest that previous findings citing Bacteroides- and Prevotella-dominated clusters are the result of an artifact caused by the greater relative abundance of these two taxa over other taxa in the human gut and the sparsity of Prevotella abundant samples.
  
  
  CONCLUSIONS
  We believe that the term "enterotypes" is misleading because it implies both an underlying consistency of community taxa and a clear separation of sets of human gut samples, neither of which is supported by the broader data. We propose the use of "biomarker" as a more accurate description of these and other taxa that correlate with diet, lifestyle, and disease state.
authors.affiliation: Brown University, Providence, RI, USA.
authors.forename: Anastassia
authors.initials: A
authors.lastname: Gorvitovskaia
authors.affiliation: Sequoia Hall, Stanford University, Stanford, CA, USA. susan@stat.stanford.edu.
authors.forename: Susan P
authors.identifier: http://orcid.org/0000-0002-2208-8168
authors.initials: SP
authors.lastname: Holmes
authors.affiliation: Indigo Agriculture Inc, Cambridge, MA, USA.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Huse
mesh_terms: D044466:Asian People; D001439:Bacteroides / Q000502:physiology*; D015415:Biomarkers / Q000032:analysis; D044383:Black People; D016000:Cluster Analysis; D004032:Diet / Q000145:classification; D000069196:Gastrointestinal Microbiome / Q000502:physiology*; D041981:Gastrointestinal Tract / Q000382:microbiology*; D006801:Humans; D008019:Life Style / Q000208:ethnology*; D018720:Prevotella / Q000502:physiology*; D025341:Principal Component Analysis; D013559:Symbiosis / Q000502:physiology; D044465:White People
chemical_list: D015415:Biomarkers
keywords: Biomarkers; Enterotypes; Human gut; Microbiome