The human microbiome: at the interface of health and disease - PubMed (original) (raw)

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The human microbiome: at the interface of health and disease

Ilseung Cho et al. Nat Rev Genet. 2012.

Abstract

Interest in the role of the microbiome in human health has burgeoned over the past decade with the advent of new technologies for interrogating complex microbial communities. The large-scale dynamics of the microbiome can be described by many of the tools and observations used in the study of population ecology. Deciphering the metagenome and its aggregate genetic information can also be used to understand the functional properties of the microbial community. Both the microbiome and metagenome probably have important functions in health and disease; their exploration is a frontier in human genetics.

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Figures

Figure 1

Figure 1. Compositional differences in the microbiome by anatomic site

High-throughput sequencing has revealed substantial intra-individual microbiome variation at different anatomical sites, and inter-individually for the same anatomical sites ,,,,,. However, higher level (e.g. phylum) taxonomic features display temporal (longitudinal) stability in individuals at specific anatomical sites. Such site-specific differences as well as observed conservation between human hosts provide an important framework to determine the biological and pathological significance of a particular microbiome composition. The figure indicates percentages of sequences at the taxonomic phylum level from selected references. Certain features, such as the presence or absence of Helicobacter pylori, can lead to permanent and marked perturbations in community composition.

Figure 2

Figure 2. Conservation of bacterial genes despite taxonomic variation

A) Turnbaugh et al. studied the distal gut microbiome in lean and obese twins and their mothers. There were substantial and significant taxonomic variations amongst the individuals, although Firmicutes and Bacteroidetes still constituted the majority of the taxa. B) Through metagenomic analyses, the functional characteristics of the microbiomeas identified by COG pathways are largely conserved, despite the taxonomic variation. COG pathways are denoted by: S – Unknown; R – General function; L – DNA; G – Carbohydrates; E – Amino acids; M – Envelope; K – Transcription; J – Translation; C – Energy; T – Signal transduction; P – Inorganic; V – Defense; H – Coenzymes; O – Protein turnover; F – Nucleotides; U – Secretion; I – Lipids; D – Cell cycle; B – Chromatin; Q – Second metabolites; N – Cell motility; W – Extracellular; Z – Cytoskeleton; A – RNA. Reproduced with permission from Turnbaugh et al, Nature and the authors © Macmillan Publishers Ltd

Figure 3

Figure 3. Acquisition of the microbiome in early life by vertical transmission and factors modifying mother-to-child microbial transmission

Through live-birth, mammals have important opportunities for mother → child microbial transmission, via direct-surface contact. However, many modern practices can reduce the organism and gene flow; several examples are illustrated. After initial introductions, there is strong selection by hosts for microbes with specific phenotypes, consistent with the extensive conservation shown in Figure 1. Acquisition is modified by offspring genetic and epigenetic differences (with respect to both maternal and paternal genes) that inform the competition for host resources by the vertically transmitted and environmentally acquired microbes. Ancestral organisms that have particular tissue- and niche-specific adaptations facilitate tissue tropisms and are selected, explaining the conserved niche-specificity compositions.

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