Dynamics of tissue and fecal microbiota in active Crohn’s disease and their ability to predict disease state

Abstract

BACKGROUND

Simultaneous assessment of gut microbiota in stool and tissue samples is crucial for a better understanding of their role in Crohn’s disease (CD), yet most reports have focused on fecal microbiota alone. Additionally, gut microbiota may serve as a clinically useful diagnostic biomarker of CD although data on this is limited.

AIM

To evaluate gut microbiota in tissue and stool samples in patients with active CD to understand the structure and function compared to healthy controls (HC). We also assessed their utility as a diagnostic biomarker of CD.

METHODS

Adult patients with active CD and HC were prospectively recruited for this study. The clinical and investigation details were recorded. Rectal mucosal biopsy and stool samples were obtained to assess the bacterial population. DNA was extracted, the V3-V4 region of the 16S rRNA gene was amplified, and library preparation was done and sequenced on the Illumina MiSeq platform. The bacterial diversity, composition, dysbiosis, predicted function, and predictors of disease state were estimated using the QIIME 2 pipeline and R packages.

RESULTS

We recruited 66 patients with CD (age 39.7 ± 11.1 years, 65.2% males) and 69 HC. Comparison of tissue with fecal microbiota in active CD showed significant differences in composition and predicted function. Both tissue and fecal microbiota from active CD showed reduced microbial diversity and compositional differences compared to HC, and disease state was a key determinant of bacterial population. Differences (CD vs HC) were noted in the abundance of several predicted synthetic and degradation pathways in both tissue and stool bacteria. Tissue microbiota was a superior predictor of active CD than stool (area under receiver operating characteristic curve 0.8 vs 0.62).

CONCLUSION

Gut microbial characteristics revealed significant structural and functional differences between CD and HC in both tissue and stool. Tissue bacteria performed well as a microbial biomarker for clinical diagnosis of CD.

Keywords: Fecal microbiota; Mucosal microbiota; Crohn’s disease; Dysbiosis; Biomarker; Functional difference

Core Tip: Gut microbiota is emerging as a key player in the pathogenesis of Crohn’s disease (CD). The mucosal gut microbiota differs in structure and function compared to fecal microbiota, yet most studies have focused on fecal microbiota alone. We evaluated both mucosal and fecal microbiota in adults with active CD and compared this with the healthy controls. Our results show striking differences in bacterial structural and functional characteristics between mucosal and fecal samples in Crohn's disease. Additionally, the mucosal microbiota proved to be a good predictor of disease state and can serve as a novel potential biomarker for diagnosis of CD.