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      A core gut microbiome in obese and lean twins

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          Abstract

          The human distal gut harbors a vast ensemble of microbes (the microbiota) that provide us with important metabolic capabilities, including the ability to extract energy from otherwise indigestible dietary polysaccharides 16. Studies of a small number of unrelated, healthy adults have revealed substantial diversity in their gut communities, as measured by sequencing 16S rRNA genes 68, yet how this diversity relates to function and to the rest of the genes in the collective genomes of the microbiota (the gut microbiome) remains obscure. Studies of lean and obese mice suggest that the gut microbiota affects energy balance by influencing the efficiency of calorie harvest from the diet, and how this harvested energy is utilized and stored 35. To address the question of how host genotype, environmental exposures, and host adiposity influence the gut microbiome, we have characterized the fecal microbial communities of adult female monozygotic and dizygotic twin pairs concordant for leanness or obesity, and their mothers. Analysis of 154 individuals yielded 9,920 near full-length and 1,937,461 partial bacterial 16S rRNA sequences, plus 2.14 gigabases from their microbiomes. The results reveal that the human gut microbiome is shared among family members, but that each person’s gut microbial community varies in the specific bacterial lineages present, with a comparable degree of co-variation between adult monozygotic and dizygotic twin pairs. However, there was a wide array of shared microbial genes among sampled individuals, comprising an extensive, identifiable ‘core microbiome’ at the gene, rather than at the organismal lineage level. Obesity is associated with phylum-level changes in the microbiota, reduced bacterial diversity, and altered representation of bacterial genes and metabolic pathways. These results demonstrate that a diversity of organismal assemblages can nonetheless yield a core microbiome at a functional level, and that deviations from this core are associated with different physiologic states (obese versus lean).

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          Error-correcting barcoded primers for pyrosequencing hundreds of samples in multiplex.

          We constructed error-correcting DNA barcodes that allow one run of a massively parallel pyrosequencer to process up to 1,544 samples simultaneously. Using these barcodes we processed bacterial 16S rRNA gene sequences representing microbial communities in 286 environmental samples, corrected 92% of sample assignment errors, and thus characterized nearly as many 16S rRNA genes as have been sequenced to date by Sanger sequencing.
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            Functional metagenomic profiling of nine biomes.

            Microbial activities shape the biogeochemistry of the planet and macroorganism health. Determining the metabolic processes performed by microbes is important both for understanding and for manipulating ecosystems (for example, disruption of key processes that lead to disease, conservation of environmental services, and so on). Describing microbial function is hampered by the inability to culture most microbes and by high levels of genomic plasticity. Metagenomic approaches analyse microbial communities to determine the metabolic processes that are important for growth and survival in any given environment. Here we conduct a metagenomic comparison of almost 15 million sequences from 45 distinct microbiomes and, for the first time, 42 distinct viromes and show that there are strongly discriminatory metabolic profiles across environments. Most of the functional diversity was maintained in all of the communities, but the relative occurrence of metabolisms varied, and the differences between metagenomes predicted the biogeochemical conditions of each environment. The magnitude of the microbial metabolic capabilities encoded by the viromes was extensive, suggesting that they serve as a repository for storing and sharing genes among their microbial hosts and influence global evolutionary and metabolic processes.
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              Genetic and environmental factors in relative body weight and human adiposity.

              We review the literature on the familial resemblance of body mass index (BMI) and other adiposity measures and find strikingly convergent results for a variety of relationships. Results from twin studies suggest that genetic factors explain 50 to 90% of the variance in BMI. Family studies generally report estimates of parent-offspring and sibling correlations in agreement with heritabilities of 20 to 80%. Data from adoption studies are consistent with genetic factors accounting for 20 to 60% of the variation in BMI. Based on data from more than 25,000 twin pairs and 50,000 biological and adoptive family members, the weighted mean correlations are .74 for MZ twins, .32 for DZ twins, .25 for siblings, .19 for parent-offspring pairs, .06 for adoptive relatives, and .12 for spouses. Advantages and disadvantages of twin, family, and adoption studies are reviewed. Data from the Virginia 30,000, including twins and their parents, siblings, spouses, and children, were analyzed using a structural equation model (Stealth) which estimates additive and dominance genetic variance, cultural transmission, assortative mating, nonparental shared environment, and special twin and MZ twin environmental variance. Genetic factors explained 67% of the variance in males and females, of which half is due to dominance. A small proportion of the genetic variance was attributed to the consequences of assortative mating. The remainder of the variance is accounted for by unique environmental factors, of which 7% is correlated across twins. No evidence was found for a special MZ twin environment, thereby supporting the equal environment assumption. These results are consistent with other studies in suggesting that genetic factors play a significant role in the causes of individual differences in relative body weight and human adiposity.
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                Author and article information

                Journal
                0410462
                6011
                Nature
                Nature
                0028-0836
                1476-4687
                24 October 2008
                30 November 2008
                22 January 2009
                22 July 2009
                : 457
                : 7228
                : 480-484
                Affiliations
                [1 ]Center for Genome Sciences, Washington University School of Medicine, St Louis MO 63108, USA
                [2 ]Department of Psychiatry, Washington University School of Medicine, St Louis MO 63108, USA
                [3 ]Department of Computer Science, University of Colorado, Boulder, CO 80309, USA
                [4 ]Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80309, USA
                [5 ]CNRS, UMR6098 Marseille, France
                [6 ]Josephine Bay Paul Center, Marine Biological Laboratory, Woods Hole, MA 02543, USA
                [7 ]Environmental Genomics Core Facility, University of South Carolina, Columbia, SC 29208, USA
                [8 ]Department of Chemistry and Biochemistry and the Advanced Center for Genome Technology, University of Oklahoma, Norman, OK 73019, USA
                [9 ]454 Life Sciences, Branford, CT 06405, USA.
                Author notes
                [* ]Correspondence and requests for materials should be addressed to J.I.G. ( jgordon@ 123456wustl.edu )
                Article
                nihpa74182
                10.1038/nature07540
                2677729
                19043404
                6f07f76d-8d45-49da-b462-c06f3b5dde3a
                History
                Funding
                Funded by: National Institute of General Medical Sciences : NIGMS
                Funded by: National Institute of Child Health & Human Development : NICHD
                Funded by: National Institute on Alcohol Abuse and Alcoholism : NIAAA
                Funded by: National Institute of Environmental Health Sciences : NIEHS
                Funded by: National Institute of Diabetes and Digestive and Kidney Diseases : NIDDK
                Award ID: T32 GM065103-07 ||GM
                Funded by: National Institute of General Medical Sciences : NIGMS
                Funded by: National Institute of Child Health & Human Development : NICHD
                Funded by: National Institute on Alcohol Abuse and Alcoholism : NIAAA
                Funded by: National Institute of Environmental Health Sciences : NIEHS
                Funded by: National Institute of Diabetes and Digestive and Kidney Diseases : NIDDK
                Award ID: R01 HD049024-01 ||HD
                Funded by: National Institute of General Medical Sciences : NIGMS
                Funded by: National Institute of Child Health & Human Development : NICHD
                Funded by: National Institute on Alcohol Abuse and Alcoholism : NIAAA
                Funded by: National Institute of Environmental Health Sciences : NIEHS
                Funded by: National Institute of Diabetes and Digestive and Kidney Diseases : NIDDK
                Award ID: R01 AA009022-10 ||AA
                Funded by: National Institute of General Medical Sciences : NIGMS
                Funded by: National Institute of Child Health & Human Development : NICHD
                Funded by: National Institute on Alcohol Abuse and Alcoholism : NIAAA
                Funded by: National Institute of Environmental Health Sciences : NIEHS
                Funded by: National Institute of Diabetes and Digestive and Kidney Diseases : NIDDK
                Award ID: P50 ES012742-049001 ||ES
                Funded by: National Institute of General Medical Sciences : NIGMS
                Funded by: National Institute of Child Health & Human Development : NICHD
                Funded by: National Institute on Alcohol Abuse and Alcoholism : NIAAA
                Funded by: National Institute of Environmental Health Sciences : NIEHS
                Funded by: National Institute of Diabetes and Digestive and Kidney Diseases : NIDDK
                Award ID: P30 DK056341-08 ||DK
                Funded by: National Institute of General Medical Sciences : NIGMS
                Funded by: National Institute of Child Health & Human Development : NICHD
                Funded by: National Institute on Alcohol Abuse and Alcoholism : NIAAA
                Funded by: National Institute of Environmental Health Sciences : NIEHS
                Funded by: National Institute of Diabetes and Digestive and Kidney Diseases : NIDDK
                Award ID: P30 DK056341-07 ||DK
                Funded by: National Institute of General Medical Sciences : NIGMS
                Funded by: National Institute of Child Health & Human Development : NICHD
                Funded by: National Institute on Alcohol Abuse and Alcoholism : NIAAA
                Funded by: National Institute of Environmental Health Sciences : NIEHS
                Funded by: National Institute of Diabetes and Digestive and Kidney Diseases : NIDDK
                Award ID: P01 DK078669-01 ||DK
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