Microbiome in IBD: what do we know?

IBD, including Crohn’s disease and ulcerative colitis affects millions of people and is increasing in incidence worldwide. It is characterized by immune-mediated intestinal inflammation, driven by genetic predisposition and environmental factors (ie. diet, antibiotic use, socioeconomic development)

General consensus exists that inflammatory bowel disease (IBD) is associated with compositional and metabolic changes in the gut microbiota, leading it to dysbiosis. However, a direct causal relationship between dysbiosis and IBD, as with other diseases, has not been established in humans. 

Microbiome in IBD pathogenesis

That the gut microbiota plays a role in the pathogenesis of IBD has long been postulated. This has been supported by various observations:

1. IBD can respond to antibiotic treatment

2. Predisposition of inflammation in regions with faecal stasis (terminal ileum and rectum)

3. Effectiveness of faecal diversion in Cronh’s disease

4. Increase in incidence associated with industrialization, changes in environment and diet

Nevertheless, it is difficult to study the microbiome in humans, especially in IBD patients. Limitations, that extend across most studies in the field, include:

1. Wide clinical spectrum of CD and UC can’t be represented by single studies

2. Many microbial taxa are difficult to culture

3. Microbiota composition widely differ between faecal and mucosal samples

4. Most studies focus on composition rather than microbial function

5. Research can be confounded by active treatments

Changes in microbiome composition

Studies have shown differences between healthy and IBD patients regarding the composition of gut microbiota. The phylum Firmicutes is often reduced in proportional abundance, and the Proteobacteria phylum (ie. E. coli) is increased. 

The timeline of the gut changes is not well established. Studies have shown dysbiosis in pediatric patients, suggesting it may play a role in the onset of the disease. 

Evidence for the existence of specific pathogens causing IBD is limited, but correlations have been found between certain strains of invasive E. coli and Crohn’s disease, for example. 

Changes in microbiome function

Changes in the gut microbiota composition can lead to metabolite alterations that are likely to have a role in IBD pathogenesis. 12% of metabolic pathways are different in IBD patients. Aminoacid biosynthesis and carbohydrate metabolism pathways were reduced, in favor of nutrient uptake, virulence and secretion pathways. 

These reflect the microbial response to the inflammatory intestinal environment and are possibly more informative than what composition reflects. Dysbiosis affects the hosts in additional ways: bile production and SCFA production.

Effect of IBD medication on microbiome

Medication for IBD also affects the composition of gut microbiota. Nevertheless, favorable changes in microbiome might be due to the medication or a result of the improvement of intestinal inflammation. 

Treatment strategies for dysbiosis

The gut microbiome has been on the spot as a possible therapeutic target. To this day, there are two main treatment options: probiotics or fecal microbiome transplantation.