Review Article

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

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

Disclosures

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

In This Article

Conclusions/Future Perspectives

It is now clear that inflammatory bowel disease is intimately linked to changes in the composition of the gut microbiota. The existing therapeutic approaches presented in this review broadly fall into 3 categories, namely: accession (faecal microbial transplantation and probiotics), reduction (antibiotics) or indirect modulation (exclusive enteral nutrition and prebiotics; Figure 2).[179] In paediatric patients, exclusive enteral nutrition is an established treatment in CD and the focus should now be on maximising the evidence supporting this strategy and bringing this into clinical practice. The available evidence for other strategies is sparse and should only be implemented within the clinical trial setting. In adults, faecal microbial transplantation appears to hold the most promise, with several randomised control trials reporting clinical efficacy. However, the differences in study design and methodology mean that it is currently not possible to elegantly translate these results into clinical practice. Faecal microbial transplantation dramatically alters the structure and function of the whole microbial community, which means that faecal microbial transplantation could have therapeutic effects on numerous host targets. There are, however, many unanswered questions and, in the light of the fact that our understanding of what constitutes a healthy microbiota is still in its infancy, a robust donor selection and screening program is essential. Future research should focus on standardising faecal microbiota processing protocols and placebo selection. Furthermore, it is now incumbent on researchers to focus on the stratification of responders and detailed interrogation of the associated microbial changes in these patients. This will be fundamental in unravelling the pathogenesis of inflammatory bowel disease and the mechanism of action of faecal microbial transplantation. Multifaceted longitudinal observation of patients before, during and after treatment as well as robust randomised controlled trials will need to be performed to refine and improve on the evidence that is currently available.

Figure 2.

The future of microbiome-modulating therapeutics. Existing therapeutic approaches to modulate the gut microbiome are relatively unrefined and primitive, broadly falling into 3 categories, namely: accession (faecal microbiota transplantation and probiotics), reduction (antibiotics) or indirect modulation (exclusive enteral nutrition and prebiotics). Future therapeutic approaches will be more targeted and personalised to treat the underlying disease pathophysiology. Strategies that are currently being investigated include live biotherapeutics containing single strains or consortia of bacteria that have been rationally selected and bacteria that have been engineered to produce therapeutic proteins. Alongside this, developing personalised dietary manipulation strategies and small molecule delivery will also likely feature

The existing therapeutic approaches to modulate the gut microbiome are relatively unrefined and primitive (Figure 2). However, looking forward, the future of microbiome modulating therapeutics looks bright. There are several novel strategies and technologies hurtling towards the clinic. In an effort to develop a more specific form of faecal microbial transplantation, many groups are pursuing single strains of live organisms or characterised communities of microbes (Figure 2).[180,181] Other groups are taking an even more reductionist approach by mining bacteria for small molecules.[182] Finally, advances in the field of synthetic biology may mean that one day each of us will be able to colonise our gut with genetically modified bacteria that knock out "bad bugs" with bacteriophages or secrete anti-inflammatory small molecules. Taken collectively, it is clear that ignoring the microbiome in inflammatory bowel disease is not an option and the current treatment paradigm is on course to change dramatically.

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