New research supports the contribution of the gut microbiota in Crohn’s disease pathogenesis

The fact that healthy relatives of patients with inflammatory bowel disease (IBD) have a higher risk of developing IBD and display mucosal microbiota dysbiosis indicates that both genetic background and alterations of the gut microbiome might trigger disease phenotype.

A study, led by Prof. Kevin Whelan from the Faculty of Life Sciences & Medicine at King’s College London (United Kingdom), has found that healthy people at risk of Crohn’s disease exhibit a mucosa-associated microbiota dysbiosis with a lower abundance of Faecalibacterium prausnitzii.

The researchers studied the influence of genotypic and phenotypic factors on the gut microbiota and characterized the mucosal microbiota in 21 patients with quiescent Crohn’s disease (CD), 17 young healthy siblings of CD patients and 19 unrelated healthy controls.

The core gut microbiota of both CD patients and their healthy siblings were significantly less diverse compared with healthy unrelated controls. Indeed, the composition of the whole and core microbiota was more similar between patients and their healthy siblings than between healthy siblings and healthy controls. These findings suggest that gut microbiota dysbiosis in healthy but genetically predisposed relatives of CD patients might influence disease pathogenesis, rather than merely being a consequence of the established disease.

Reduced Faecalibacterium prausnitzii contributed the most to mucosa-associated microbiota composition difference between patients and siblings when compared with controls. In line with these results, the same researchers have shown in a previous study that fecal concentrations of F. prausnitzii, Clostridial cluster IV, Ruminococci and Roseburia spp. were significantly lower in patients and siblings compared with controls. In contrast, in pediatric populations, an increase in F. prausnitzii has been reported, which does not allow for clear conclusions regarding the role of this bacterium in CD development and pathogenesis. The researchers hypothesized on the paper that this sibling mucosa-associated microbiota dysbiosis may represent an incomplete version of the full CD dysbiosis, which deserves further exploration in long-term longitudinal studies.

On the other hand, increased Escherichia coli contributed to the dissimilarity between patients and healthy controls, which suggest this change might be a consequence of chronic intestinal inflammation in patients with CD.

The researchers also sought to study the influence of genotypic and phenotypic factors on gut microbiota dysbiosis in patients with CD and their healthy relatives. Among phenotype and genotype markers of CD risk that can influence microbiota variation between and within groups, genotype—a composite score of genotypic risk across 72 loci related with CD—had the strongest effect on microbiota variation between and within patients, healthy siblings and controls.

In conclusion, this study shows that alterations in the mucosal gut microbiota composition may occur both in patients with CD and in their healthy relatives. These findings highlight that the microbiota dysbiosis is not only a consequence of inflammation, but that it may also play a relevant role in CD pathogenesis.

 

Reference:

Hedin CR, van der Gast CJ, Stagg AJ, et al. The gut microbiota of siblings offers insights into microbial pathogenesis of inflammatory bowel disease. Gut Microbes. 2017; 8(4):359-65. doi: 10.1080/19490976.2017.1284733.

Andreu Prados
Andreu Prados
Andreu Prados holds a Bachelor of Science Degree in Pharmacy & Human Nutrition and Dietetics. Science writer specialised in gut microbiota and probiotics, working also as lecturer and consultant in nutrition and healthcare. Follow Andreu on Twitter @andreuprados