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Review
. 2019 Aug;17(8):497-511.
doi: 10.1038/s41579-019-0213-6.

Microbial genes and pathways in inflammatory bowel disease

Melanie Schirmer  1 , Ashley Garner  2 , Hera Vlamakis  3   4 , Ramnik J Xavier  5   6
Affiliations
Review

Microbial genes and pathways in inflammatory bowel disease

Melanie Schirmer et al. Nat Rev Microbiol. 2019 Aug.

Abstract

Perturbations in the intestinal microbiome are implicated in inflammatory bowel disease (IBD). Studies of treatment-naive patients have identified microbial taxa associated with disease course and treatment efficacy. To gain a mechanistic understanding of how the microbiome affects gastrointestinal health, we need to move from census to function. Bacteria, including those that adhere to epithelial cells as well as several Clostridium species, can alter differentiation of T helper 17 cells and regulatory T cells. Similarly, microbial products such as short-chain fatty acids and sphingolipids also influence immune responses. Metagenomics and culturomics have identified strains of Ruminococcus gnavus and adherent invasive Escherichia coli that are linked to IBD and gut inflammation. Integrated analysis of multiomics data, including metagenomics, metatranscriptomics and metabolomics, with measurements of host response and culturomics, have great potential in understanding the role of the microbiome in IBD. In this Review, we highlight current knowledge of gut microbial factors linked to IBD pathogenesis and discuss how multiomics data from large-scale population studies in health and disease have been used to identify specific microbial strains, transcriptional changes and metabolic alterations associated with IBD.

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Conflict of interest statement

Competing interests

The authors declare no competing interests.

Supplementary information

Supplementary information is available for this paper at https://doi.org/10.1038/s41579-019-0213-6.

Figures

Figure 1:
Figure 1:. Inflammatory bowel disease and the microbiota.
In health, gut bacterial composition (anaerobes and facultative anaerobes) is maintained in balance with host cell physiology. Alterations in gut microbiome composition during disease include reduced microbial diversity and expansion of facultative anaerobes due to increased nitrosative and oxidative stress in the gut. Current standard treatments, such as 5ASA mesalamine, corticosteroids, immunomodulators, and anti-TNFα biologic therapy, focus on treating and controlling disease symptoms, in particular chronic inflammation.
Figure 2.
Figure 2.. Phylogenetic tree of bacterial species associated with inflammatory bowel disease.
Multiple studies have implicated bacterial species in inflammatory bowel disease (IBD); however, results differ between studies. The association results from metagenomic studies have been summarized in a phylogenetic tree to highlight common pattern across studies. The phylogenetic tree (generated using the software GraPhlAn) was constructed based on all bacterial species identified in samples from PRISM (n=159), LSS (n=271), Lewis, (n=368), and NLIBD in combination with LLDeep controls (n=1,380) and includes all species that were detected in at least 20 samples (nspecies=726). Colored tree leaves indicate species that were differentially abundant (false discovery rate <0.1) in at least two studies, with 6 increased (red circles) and 26 decreased (blue circles) species. The outer rings indicate study-specific results and highlight all microorganisms identified in the respective study (Supplementary Table 1 lists the differentially abundant species for each study, respectively). Background colours indicate all species that belong to the same phylum.
Figure 3.
Figure 3.. Microbiome-based therapies for inflammatory bowel disease.
Microbiome-based therapies for inflammatory bowel disease aim to restore the gut microbial balance, which includes increasing microbial diversity, in particular anaerobic bacteria, reducing facultative anaerobes, and reducing gut inflammation (part a). Current and developing treatments either alter nutrition, administer microbial organisms and/or metabolites, or directly target microorganisms and/or pathways (part b). The effects of these treatments, including reduction of gut inflammation and alterations of the gut microbial communities and metabolites, are either direct or indirect. AIEC, adhesive invasive Escherichia coli.
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