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   Nature. Author manuscript; available in PMC 2012 Dec 14.    
      
   Published in final edited form as:    
   Nature. 2012 May 9; 486(7402): 222–227.    
      
   Published online 2012 May 9. doi:  10.1038/nature11053    
   PMCID: PMC3376388    
   NIHMSID: NIHMS365354    
      
      
   Human gut microbiome viewed across age and geography    
      
   Tanya Yatsunenko,1 Federico E. Rey,1 Mark J. Manary,2 Indi Trehan,2 Maria   
   Gloria Dominguez-Bello,4 Monica Contreras,5 Magda Magris,6 Glida Hidalgo,6   
   Robert N. Baldassano,7 Andrey P. Anokhin,3 Andrew C. Heath,3 Barbara Warner,2   
   Jens Reeder,8 Justin    
   Kuczynski,8 J. Gregory Caporaso,8,* Catherine A. Lozupone,8 Christian Lauber,8   
   Jose Carlos Clemente,8 Dan Knights,8 Rob Knight,8,9 and Jeffrey I. Gordon1    
   Author information ► Copyright and License information ►   
   The publisher's final edited version of this article is available at Nature    
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   Abstract    
   Gut microbial communities represent one source of human genetic and metabolic   
   diversity. To examine how gut microbiomes differ between human populations   
   when viewed from the perspective of component microbial lineages, encoded   
   metabolic functions, stage    
   of postnatal development, and environmental exposures, we characterized   
   bacterial species present in fecal samples obtained from 531 individuals   
   representing healthy Amerindians from the Amazonas of Venezuela, residents of   
   rural Malawian communities, and    
   inhabitants of USA metropolitan areas, as well as the gene content of 110 of   
   their microbiomes. This cohort encompassed infants, children, teenagers and   
   adults, parents and offspring, and included mono- and dizygotic twins. Shared   
   features of the    
   functional maturation of the gut microbiome were identified during the first   
   three years of life in all three populations, including age-associated changes   
   in the representation of genes involved in vitamin biosynthesis and   
   metabolism. Pronounced    
   differences in bacterial species assemblages and functional gene repertoires   
   were noted between individuals residing in the USA compared to the other two   
   countries. These distinctive features are evident in early infancy as well as   
   adulthood. In addition,   
    the similarity of fecal microbiomes among family members extends across   
   cultures. These findings underscore the need to consider the microbiome when   
   evaluating human development, nutritional needs, physiological variations, and   
   the impact of    
   Westernization.    
      
   Genetic variation between human populations is typically viewed as differences   
   in the allele frequencies of shared Homo sapiens genes. Another source of   
   genetic and metabolic diversity resides in differences in the representation   
   of the millions of genes    
   and myriad gene functions within our gut microbial communities1–3. Sampling   
   a broad population of healthy humans representing different ages and cultural   
   traditions offers an opportunity to discover how our gut microbiomes evolve   
   within a lifespan,    
   vary between populations, and respond to our changing lifestyles4–9.   
   Therefore, we conducted a demonstration project to address the question of   
   whether there are discernible patterns of functional maturation of the gut   
   communities of healthy infants    
   and children living in geographically and culturally distinct settings.    
      
   Fecal samples were obtained from individuals in families of Guahibo   
   Amerindians residing in two villages (Platanillal and Coromoto), separated by   
   10 miles, located near Puerto Ayacucho in the Amazonas State of Venezuela (see   
   Table S1a,b for information    
   about their diets). Fecal samples were also procured from members of families   
   living in four rural communities of Malawi located within 10–70 miles of one   
   another (Chamba, Makwhira, Mayaka, Mbiza). Lifestyles in these villages are   
   very similar, and    
   diets are relatively monotonous, dominated by maize (Table S1c). In addition,   
   we sampled families distributed across the USA, including the greater   
   metropolitan areas of St. Louis, Philadelphia and Boulder. The sampled   
   populations included parents and    
   siblings, and, in the USA and Malawi, monozygotic (MZ) and dizygotic (DZ) twin   
   pairs. A total of 531 individuals (151 families) were studied: 115 individuals   
   (34 families) from Malawi; 100 individuals (19 families) from Venezuela; and   
   316 individuals (98    
   families) from the USA (see Table S2 for subject characteristics; note that   
   all except 35 adults and one child from the USA were explicitly recruited for   
   this study).    
      
   DNA was extracted from a single fecal sample donated by each person. Variable   
   region 4 (V4) of bacterial 16S rRNA genes present in each fecal community was   
   amplified by PCR and the resulting amplicons sequenced on an Illumina HiSeq   
   2000 instrument (n=1,   
   803,250±562,877 reads/fecal sample; 1,093,740,274 total reads, Table S2a) to   
   define the phylogenetic types (phylotypes) present. Species-level bacterial   
   phylotypes were defined as organisms sharing ≥97% nucleotide sequence   
   identity (%ID) in the V4    
   regions of their 16S rRNA genes10. In addition, we characterized functions   
   encoded in community DNA by performing multiplex shotgun 454 pyrosequencing of   
   fecal DNA from a subset of 110 fecal samples, encompassing 43 families with   
   members matched as    
   closely as possible for age (155,890±87,083 reads/sample; total size of   
   dataset, 5.9 Gb; Table S2b). The resulting shotgun reads were annotated with   
   KEGG Orthology group (KO) assignments and with enzyme classification (EC)   
   numbers (KEGG version 58).    
      
   Go to:    
   Changes in the taxonomic/phylogenetic composition of fecal communities as a   
   function of age and population    
      
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