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      Implications of the Human Microbiome Project for Epidemiology

        ,
      American Journal of Epidemiology
      Oxford University Press (OUP)

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          Abstract

          The structure and function of microorganisms that live in and on us, the human microbiota, are a tremendous resource. Microbiota may help to explain individual variability in health outcomes and be a source of new biomarkers for environmental exposures and of novel prognostic and diagnostic indicators. The increase in availability of low-cost, high-throughput techniques makes it relatively straightforward to include microbiota assessments in epidemiologic studies. With the recent joint publications of the findings of the Human Microbiome Consortium and related studies, the consequent surge of interest in microbiome research, and remarkable media attention, the time is ripe for epidemiologists to contribute their expertise to and translate results of microbiota research for population health.

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          Most cited references28

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          A Metagenomic Approach to Characterization of the Vaginal Microbiome Signature in Pregnancy

          While current major national research efforts (i.e., the NIH Human Microbiome Project) will enable comprehensive metagenomic characterization of the adult human microbiota, how and when these diverse microbial communities take up residence in the host and during reproductive life are unexplored at a population level. Because microbial abundance and diversity might differ in pregnancy, we sought to generate comparative metagenomic signatures across gestational age strata. DNA was isolated from the vagina (introitus, posterior fornix, midvagina) and the V5V3 region of bacterial 16S rRNA genes were sequenced (454FLX Titanium platform). Sixty-eight samples from 24 healthy gravidae (18 to 40 confirmed weeks) were compared with 301 non-pregnant controls (60 subjects). Generated sequence data were quality filtered, taxonomically binned, normalized, and organized by phylogeny and into operational taxonomic units (OTU); principal coordinates analysis (PCoA) of the resultant beta diversity measures were used for visualization and analysis in association with sample clinical metadata. Altogether, 1.4 gigabytes of data containing >2.5 million reads (averaging 6,837 sequences/sample of 493 nt in length) were generated for computational analyses. Although gravidae were not excluded by virtue of a posterior fornix pH >4.5 at the time of screening, unique vaginal microbiome signature encompassing several specific OTUs and higher-level clades was nevertheless observed and confirmed using a combination of phylogenetic, non-phylogenetic, supervised, and unsupervised approaches. Both overall diversity and richness were reduced in pregnancy, with dominance of Lactobacillus species (L. iners crispatus, jensenii and johnsonii, and the orders Lactobacillales (and Lactobacillaceae family), Clostridiales, Bacteroidales, and Actinomycetales. This intergroup comparison using rigorous standardized sampling protocols and analytical methodologies provides robust initial evidence that the vaginal microbial 16S rRNA gene catalogue uniquely differs in pregnancy, with variance of taxa across vaginal subsite and gestational age.
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            Regulated virulence controls the ability of a pathogen to compete with the gut microbiota.

            The virulence mechanisms that allow pathogens to colonize the intestine remain unclear. Here, we show that germ-free animals are unable to eradicate Citrobacter rodentium, a model for human infections with attaching and effacing bacteria. Early in infection, virulence genes were expressed and required for pathogen growth in conventionally raised mice but not germ-free mice. Virulence gene expression was down-regulated during the late phase of infection, which led to relocation of the pathogen to the intestinal lumen where it was outcompeted by commensals. The ability of commensals to outcompete C. rodentium was determined, at least in part, by the capacity of the pathogen and commensals to grow on structurally similar carbohydrates. Thus, pathogen colonization is controlled by bacterial virulence and through competition with metabolically related commensals.
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              Experimental and analytical tools for studying the human microbiome.

              The human microbiome substantially affects many aspects of human physiology, including metabolism, drug interactions and numerous diseases. This realization, coupled with ever-improving nucleotide sequencing technology, has precipitated the collection of diverse data sets that profile the microbiome. In the past 2 years, studies have begun to include sufficient numbers of subjects to provide the power to associate these microbiome features with clinical states using advanced algorithms, increasing the use of microbiome studies both individually and collectively. Here we discuss tools and strategies for microbiome studies, from primer selection to bioinformatics analysis.
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                Author and article information

                Journal
                American Journal of Epidemiology
                Oxford University Press (OUP)
                1476-6256
                0002-9262
                February 1 2013
                February 01 2013
                January 7 2013
                February 1 2013
                February 01 2013
                January 7 2013
                : 177
                : 3
                : 197-201
                Article
                10.1093/aje/kws449
                3626050
                23296358
                2de219b8-a9fc-44de-9a14-47fab4d52670
                © 2013
                History

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