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      Human gut microbiome viewed across age and geography

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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.

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          Most cited references20

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          Mucosal glycan foraging enhances fitness and transmission of a saccharolytic human gut bacterial symbiont.

          The distal human gut is a microbial bioreactor that digests complex carbohydrates. The strategies evolved by gut microbes to sense and process diverse glycans have important implications for the assembly and operation of this ecosystem. The human gut-derived bacterium Bacteroides thetaiotaomicron forages on both host and dietary glycans. Its ability to target these substrates resides in 88 polysaccharide utilization loci (PULs), encompassing 18% of its genome. Whole genome transcriptional profiling and genetic tests were used to define the mechanisms underlying host glycan foraging in vivo and in vitro. PULs that target all major classes of host glycans were identified. However, mucin O-glycans are the principal host substrate foraged in vivo. Simultaneous deletion of five genes encoding ECF-sigma transcription factors, which activate mucin O-glycan utilization, produces defects in bacterial persistence in the gut and in mother-to-offspring transmission. Thus, PUL-mediated glycan catabolism is an important component in gut colonization and may impact microbiota ecology.
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            What are the consequences of the disappearing human microbiota?

            Humans and our ancestors have evolved since the most ancient times with a commensal microbiota. The conservation of indicator species in a niche-specific manner across all of the studied human population groups suggests that the microbiota confer conserved benefits on humans. Nevertheless, certain of these organisms have pathogenic properties and, through medical practices and lifestyle changes, their prevalence in human populations is changing, often to an extreme degree. In this Essay, we propose that the disappearance of these ancestral indigenous organisms, which are intimately involved in human physiology, is not entirely beneficial and has consequences that might include post-modern conditions such as obesity and asthma.
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              A molecular sensor that allows a gut commensal to control its nutrient foundation in a competitive ecosystem.

              Little is known about how members of the indigenous microflora interact with their mammalian hosts to establish mutually beneficial relationships. We have used a gnotobiotic mouse model to show that Bacteroides thetaiotaomicron, a component of the intestinal microflora of mice and humans, uses a repressor, FucR, as a molecular sensor of L-fucose availability. FucR coordinates expression of an operon encoding enzymes in the L-fucose metabolic pathway with expression of another locus that regulates production of fucosylated glycans in intestinal enterocytes. Genetic and biochemical studies indicate that FucR does this by using fucose as an inducer at one locus and as a corepressor at the other locus. Coordinating this commensal's immediate nutritional requirements with production of a host-derived energy source is consistent with its need to enter and persist within a competitive ecosystem.
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                Author and article information

                Journal
                0410462
                6011
                Nature
                Nature
                Nature
                0028-0836
                1476-4687
                22 March 2012
                09 May 2012
                14 December 2012
                : 486
                : 7402
                : 222-227
                Affiliations
                [1 ]Center for Genome Sciences and Systems Biology, Washington University in St. Louis
                [2 ]Department of Pediatrics, Washington University in St. Louis
                [3 ]Department of Psychiatry, Washington University in St. Louis
                [4 ]Department of Biology, University of Puerto Rico Rio Piedras, Puerto Rico
                [5 ]Venezuelan Institute of Scientific Research (IVIC), Caracas
                [6 ]Venezuela, Amazonic Center for Research and Control of Tropical Diseases (CAICET), Puerto Ayacucho, Amazonas, Venezuela
                [7 ]Department of Pediatrics, University of Pennsylvania
                [8 ]Department of Chemistry and Biochemistry, University of Colorado, Boulder
                [9 ]Howard Hughes Medical Institute, University of Colorado, Boulder
                Author notes
                Address correspondence to: jgordon@ 123456wustl.edu
                [*]

                Current address: Department of Computer Science, Northern Arizona University, Flagstaff, AZ 86011, USA

                Article
                NIHMS365354
                10.1038/nature11053
                3376388
                22699611
                57e39bcb-5e39-40bc-ae9a-6f8fdea2986e

                Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms

                History
                Funding
                Funded by: National Institute of Diabetes and Digestive and Kidney Diseases : NIDDK
                Award ID: P01 DK078669-05 || DK
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