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

Defining the Gut Microbiota in Inflammatory Bowel Disease

A change in the normal gut microbiota with a shift away from host:microbial mutualism has been reported in many IBD studies; however, the vast majority of studies to date have focussed on bacterial changes and only recently has consideration of fungal and viral constituents been forthcoming. Some bacterial changes appear to be clearly linked to either CD or ulcerative colitis, while others appear to be attributed more generally to IBD.[14–20] The most consistent changes are reduction in biodiversity (lower number of species), with lower proportions of Firmicutes, consistently reported alongside increases in Proteobacteria[16,21–24] and Bacteroidetes phylum members[19] although reductions have also been reported.[15] Spatial re-organisation of Bacteroides species has also been documented with higher proportions of Bacteroides fragilis being seen in IBD patients.[20] In CD, changes in Firmicutes have particularly documented changes in Faecalibacterium prausnitzii.[25]Faecalibacterium prausnitzii levels have been consistently lower in ileal CD patients, although increases were noted in paediatric CD, potentially suggesting that further assessment is required.[26–28] Additional interrogation of F. prausnitzii has identified that F. prausnitzii populations are patient-specific and there are differing functional capabilities between strains with the tantalising potential that differing phylotypes may be having opposing effects.[28]

Increases in Proteobacteria, especially Escherichia coli, including pathogenic variants, are also reported in ileal CD.[29] Changes in bacterial functional capabilities have been seen in ileal CD with alterations in bacterial carbohydrate metabolism, bacterial:host interactions and host secreted enzymes noted.[30] Perturbations to the structure of the gut microbiota, termed "dysbiosis," have also been shown to impart functional changes within the host creating a pro-inflammatory state.[31] More broadly, microbial functional changes associated with inflammatory bowel disease have identified enrichment in host metabolite uptake, oxidative stress tolerance and immune evasion, alongside decreases in microbial metabolism, including short chain fatty acid (SCFA) biosynthesis and amino acid biosynthesis. Put simply, the changes seen in gut microbial structure are associated with major metabolic impairments, which impart huge functional consequences to the host. Therefore, modulation of gut microbiota, through diet, antibiotics, prebiotics, probiotics and faecal microbiota transplantation (FMT), represent, at least theoretically, a promising therapeutic avenue for the management of inflammatory bowel disease, although available evidence suggest that fine tuning of our therapeutic offerings is still needed (Figure 1).[32] Being able to harness this potential is the fundamental basis of emerging therapeutic approaches to inflammatory bowel disease management, with microbial modulation becoming a major consideration in inflammatory bowel disease management over the last decade.

Figure 1.

Current microbial therapeutic mechanisms of action. Modulation of gut microbiota through diet, antibiotics, prebiotics, probiotics and faecal microbiota transplantation, which reflects the existing microbial therapeutic avenues for inflammatory bowel disease management. The evidence for use of the existing approaches depends on the type of disease present, with ulcerative colitis appearing to benefit most from approaches, such as faecal microbiota transplantation, which dramatically alters gut microbial community structure and function. Dietary modulation through exclusive enteral nutrition demonstrates success in paediatric Crohn's disease and is thought to work by reducing the bacterial diversity within the gut. Overall, however, the balance of evidence suggests that fine tuning of our therapeutic offerings is still needed

Potential drawbacks of most of the current literature, in terms of defining microbial changes in inflammatory bowel disease, are that studies have primarily reported on cohorts with established disease and they often fail to appreciate that mucosal and faecal microbiota are different. The confounding impact of therapeutic regimes (often complex and evolving), disease chronicity and also surgical intervention make it challenging to decipher whether taxonomic changes reflect disease-driven changes or are merely a response to a drastically altered intestinal environment. In order to address this a small number of studies looking at the microbiota of newly diagnosed patients have been published. The first study looked at mucosa-associated changes in newly diagnosed children (13 CD and 12 ulcerative colitis patients), all of whom were assessed at first presentation of active disease. However, importantly for microbiome analysis, the patients had not received systemic antibiotics or steroids in the 3 months prior to investigation or immunosuppression at any time.[33] Microbial diversity was significantly reduced in CD patients, compared to ulcerative colitis and control patients. Higher abundance of F. prausnitzii was also seen in CD patients, in marked contrast to numerous other reports.[26,28,34–37] A larger study comprising of 447 paediatric CD patients, aged 3–17 years, alongside 221 controls demonstrated that several taxa could discriminate disease phenotype, including Enterobacteriaceae, Bacteroidales, Clostridiales, Haemophilus spp., Veillonellaceae, Neisseriaceae and Fusobacteriaceae.[34] Taken collectively, these studies highlight that the microbiota changes associated with treatment naive, new-onset inflammatory bowel disease are different from established disease and require additional/further consideration. Serial follow-up of such patient cohorts potentially offers a unique opportunity to study the purest profile of inflammatory bowel disease-related microbiota changes.

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