Functional profiling of the gut microbiome in disease-associated inflammation - PubMed (original) (raw)

Review

Functional profiling of the gut microbiome in disease-associated inflammation

Daniela Börnigen et al. Genome Med. 2013.

Abstract

The microbial residents of the human gut are a major factor in the development and lifelong maintenance of health. The gut microbiota differs to a large degree from person to person and has an important influence on health and disease due to its interaction with the human immune system. Its overall composition and microbial ecology have been implicated in many autoimmune diseases, and it represents a particularly important area for translational research as a new target for diagnostics and therapeutics in complex inflammatory conditions. Determining the biomolecular mechanisms by which altered microbial communities contribute to human disease will be an important outcome of current functional studies of the human microbiome. In this review, we discuss functional profiling of the human microbiome using metagenomic and metatranscriptomic approaches, focusing on the implications for inflammatory conditions such as inflammatory bowel disease and rheumatoid arthritis. Common themes in gut microbial ecology have emerged among these diverse diseases, but they have not yet been linked to targetable mechanisms such as microbial gene and genome composition, pathway and transcript activity, and metabolism. Combining these microbial activities with host gene, transcript and metabolic information will be necessary to understand how and why these complex interacting systems are altered in disease-associated inflammation.

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Figures

Figure 1

Figure 1

A model of functional dysbiosis in the human gut microbiome during initiation and progression of complex disease. Although many current studies focus on microbial composition shifts that occur subsequent to disease establishment, it is critical to differentiate functional from structural changes in the microbiome and their distinct patterns in early versus late disease. (a) An illustration of microbial community structural changes during complex disease progression. Ordinations such as principle coordinate analysis and multidimensional scaling are commonly used to qualitatively visualize microbial community structure among multiple samples (for example, cases and controls). Ordinations project distance measures such as beta diversity among samples into fewer dimensions in such a way that the patterns of greatest change occur on the primary axes (here, x and y). However, particularly in early disease, case/control status is frequently not among the factors with most influence on inter-subject microbial variation. Conversely, later-stage inflammation can have a very large effect on microbial structure, causing other sources of variation to become visually less apparent. (b) Functional profiles of gut microbial communities remain more stable among individuals in health than do microbial profiles, and they can likewise show more concerted differential responses in early and late disease stages. In this illustration, 'case' subject samples exhibit expansion of specific metagenomically encoded functions in their microbial communities during progressive phases of inflammation, as reported in [32]. (c) Representative host histology in different phases of the inflammatory response in Crohn's colitis. Colonic crypts (ring structures) are gradually destroyed by immune infiltration as colitis progresses. Images show transverse sections of human colonic mucosa stained with hematoxylin and eosin; 100 µm scale bars are included for reference (images provided by WSG). CDAC, _Clostridium difficile_-associated diarrhea; PC, principal coordinate.

Figure 2

Figure 2

The core gut microbiome consists of stable pathways present despite variation in microbial abundances. Profiles of 118 stool samples from healthy individuals, showing the relative abundances of microbial organisms (red), inferred microbial pathways [70] (green), and microbial pathways after randomization (blue, all data from [1]). All relative abundances are shown as median and interquartile range across all samples (_y_-axis) ranked by median (_x_-axis) and square-root (sqrt) scaled for visualization. As illustrated by several studies (for example, [1,89]), a stable distribution of habitat-adapted microbial pathways is maintained on a functional level (green) rather than on a phylogenetic level (red). Random assignment of microbes to samples followed by re-inference of functional potential (blue) results in a metagenome that is more variable, more skewed, and of distinct composition from that in the observed 'core' of gut microbiome functions.

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