Review Article

The Gut Microbiome in Inflammatory Bowel Disease—Avenues for Microbial Management

J. McIlroy; G. Ianiro; I. Mukhopadhya; R. Hansen; G. L. Hold


Aliment Pharmacol Ther. 2018;47(1):26-42. 

In This Article

Abstract and Introduction


Background The concept of an altered collective gut microbiota rather than identification of a single culprit is possibly the most significant development in inflammatory bowel disease research. We have entered the "omics" era, which now allows us to undertake large-scale/high-throughput microbiota analysis which may well define how we approach diagnosis and treatment of inflammatory bowel disease (IBD) in the future, with a strong steer towards personalised therapeutics.

Aim To assess current epidemiological, experimental and clinical evidence of the current status of knowledge relating to the gut microbiome, and its role in IBD, with emphasis on reviewing the evidence relating to microbial therapeutics and future microbiome modulating therapeutics.

Methods A Medline search including items 'intestinal microbiota/microbiome', 'inflammatory bowel disease', 'ulcerative colitis', 'Crohn's disease', 'faecal microbial transplantation', 'dietary manipulation' was performed.

Results Disease remission and relapse are associated with microbial changes in both mucosal and luminal samples. In particular, a loss of species richness in Crohn's disease has been widely observed. Existing therapeutic approaches broadly fall into 3 categories, namely: accession, reduction or indirect modulation of the microbiome. In terms of microbial therapeutics, faecal microbial transplantation appears to hold the most promise; however, differences in study design/methodology mean it is currently challenging to elegantly translate results into clinical practice.

Conclusions Existing approaches to modulate the gut microbiome are relatively unrefined. Looking forward, the future of microbiome-modulating therapeutics looks bright with several novel strategies/technologies on the horizon. Taken collectively, it is clear that ignoring the microbiome in IBD is not an option.


The gut microbiota comprises a large collection of microbes and the largest within the body, reaching 10[12] cells/g of luminal contents in the colon.[1] In healthy individuals, it is dominated by 2 major bacterial phyla: Bacteroidetes and Firmicutes, with smaller representation from Proteobacteria and Actinobacteria.[2,3] We are relatively ignorant of the functional and structural contributions of microorganisms outside of gut bacteria, with only a handful of publications looking at the gut virome (viruses and bacteriophages), mycome (fungi) and other micro-eukaryotes including protozoa.[4–6] The gut microbiota performs a number of crucial functions for the host including priming the immune system, breakdown of dietary substrates inaccessible to host enzymes, and detoxification of xenobiotics.[7] The healthy gut microbiome exhibits considerable functional diversity and possesses far greater genomic potential compared to its host. Perhaps of most interest, it is inherently modifiable. The implication of this interplay between humans and microbes is that pharmacological therapies, nutrient modifications and associated interventions that are targeted at the host will also significantly impact on the gut microbiota.

Genome-wide association studies (GWAS) have now identified 235 inflammatory bowel disease (IBD)-associated susceptibility loci, substantially expanding our understanding of the biology underlying these diseases.[8,9] Early genetic studies focused on searching protein coding sequences, although it is now recognised that coding variation explains only ~20% of genetic variation associated with IBD GWAS loci.[10] These studies highlighted the pivotal role of host:microbial interactions in IBD pathogenesis, specifically identifying T-cell activation, IL-23/T helper 17 pathway, autophagy and microbial recognition.[11–13] The most recent studies have undertaken low-coverage whole genome sequencing to interrogate low-frequency variants and define how much these variants contribute to IBD susceptibility. This approach has identified a missense variant in ADCY7, with mechanistic interpretation being that loss of function reduces cAMP production leading to an excessive inflammatory response that predisposes to ulcerative colitis but not Crohn's disease (CD).[8]