Investigators Research How Variables Impact IBD Studies

A new analysis indicates that stool type is superior to biopsy results in studying inflammatory bowel disease (IBD)-associated dysbiosis.

A team, led by Lama Izzat Hasan Abdel-Rahman, MSc, Department of Microbiology and Immunology, University of Otago, assessed the reproducibility of IBD microbiome research.

Inconsistent Studies

In recent years, several studies have explored the gut microbial ecology of patients with Crohn’s disease and ulcerative colitis. However, 1 issue is IBD-associated taxa and ecological effect sizes have not been consistent between the studies.

“Overwhelming evidence suggests that the microbiome is necessary for the pathogenesis of IBD,” the authors wrote. “It is widely believed, but not universally accepted, that the number of taxa in the gut microbiome of IBD patients are reduced compared with non-IBD control subjects. Other widely reported findings include greater variation within microbiome structure (beta diversity) in IBD patients compared with control subjects, and differences in taxonomic composition in both UC and CD patients.”

Inclusion and Exclusion

In the meta-analysis, the investigators identified 13 studies and analyzed how variables like sample type—stool, biopsy, or lavage—affect results in IBD gut microbiome studies between 2012-2020. The investigators used uniform bioinformatic methods for all primary data.

The studies included in the analysis contained at least 50 human participants. The investigators also excluded studies involving microbiota-altering factors including fecal microbiota transplantation. The studies also all included a set of either healthy or non-IBD control patients, with the exception of 1 study included in the analysis.

The Results

The results show reduced alpha diversity was consistent in studies involving both patients with Crohn’s disease and ulcerative colitis. However, it was more pronounced for patients with Crohn’s disease.

Overall disease contributed significantly to the variation in beta diversity in the majority of studies. While the effect size varied here, the effect of sample type was greater than the effect of disease.

The genus most consistently associated with Crohn’s disease was Fusobacterium, but disease-associated genera were mostly inconsistent between studies. Stool studies also had a lower heterogeneity than biopsy studies, particularly for Crohn’s disease.

“Although we found few consistent taxonomic differences across UC and CD datasets, our results show that IBD has a consistent effect on ecosystem alpha and beta diversity and suggest that stool type may be superior to biopsy in representing IBD-associated dysbiosis due to decreased heterogeneity,” the authors wrote. “We further demonstrate the benefit of applying updated bioinformatic methods to historic data.”

Geographic Location

Geographic location may be a bigger factor in gut microbiota composition than whether or not the individual has IBD, according to data from the 2022 European Crohn’s and Colitis Organisation annual meeting.

A team, led by J. Hu, Icahn School of Medicine at Mount Sinai, Department of Genetics and Genomic Sciences, identified gut microbiome compositions for pregnant women and infants in Hong Kong and the US with or without IBD.

Pregnant women without IBD in Hong Kong had a higher abundance of 15 taxa at the genus level including Bifidobacterium, Faecalibacterium and Bacteroides compared to pregnant women in the US without IBD. On the other hand, pregnant women without IBD in Hong Kong had a lower abundance of 6 taxa including Blautia and Turicibacter in comparison with pregnant women in the US without IBD.

For the infants born to women without IBD, those in Hong Kong had a higher abundance of 3 taxa including Klebstella and Escherichia/Shigella and lower abundance of Enterococcus in comparison with infants born to women without IBD in the US. After comparing the gut microbiome alpha-diversity of both groups of women and infant, both were lower in Hong Kong (with IBD: P = 0.077; without IBD: P = 0.13) and in the US (with IBD: P = 0.0024; without IBD: P = 0.019).

The study, “Searching for a Consensus Among Inflammatory Bowel Disease Studies: A Systematic Meta-Analysis,” was published online in Inflammatory Bowel Diseases.