Background: Microbial shifts have been associated with disease activity in Crohn's disease (CD), but findings on specific taxa are not always consistent. This may be due to differences in populations included, molecular methods applied, potential confounders and the use of cross-sectional study designs. We aimed to prospectively examine the fecal microbiota, by means of next-generation sequencing, in adult well-characterized CD patients with either changing or stable disease course over time.
Methods: Fecal samples were collected at two time points from 15 healthy individuals (HC), 35 CD patients with stable disease course (remission) and 22 CD patients during remission and subsequent exacerbation. The microbial composition was assessed by sequencing of the V4-region of the 16S rRNA gene. The microbial diversity and richness of fecal samples was assessed by the Shannon index and PD whole tree and the observed species and Chao1 index, respectively. Stability of the microbiota composition within individuals as well as differences in the microbiota composition between individuals were assessed by Bray-Curtis dissimilarity and (un)weighted Unifrac distance.
Results: CD patients at baseline had a significantly lower microbial (median (IQR)) richness (Chao1 index (644.7 (440.1–817.2) and 800.4 (711.0–849.7), respectively; p=0.004) and diversity (Shannon index; 6.0 (5.0–6.4) and 6.3 (6.1–7.1), respectively; p=0.014) as compared to HC. However, the microbial richness and diversity did not significantly change over time in CD patients that subsequently developed an exacerbation when compared to HC and CD patients that remained in remission.
When assessing the overall microbial community structure at baseline, a subset of CD patients clustered apart from HC and were characterized by a low microbial diversity and a low relative abundance of Faecalibacterium spp. Moreover, the microbiota of both CD patients that maintained in remission (RR) and those that developed an exacerbation (RA) was less stable over time when compared to HC [(unweighted Unifrac median (IQR) RR 0.40 (0.36–0.44), RA 0.38 (0.36–0.42), HC 0.35 (0.31–0.37)]. However, no differences in microbiota stability were observed between these two patient groups (p=0.39), nor was the stability impacted by medication use.
Conclusions: CD patients showed a lower temporal stability than healthy controls, but this was not affected by differences in disease course. Furthermore, a subgroup of CD patients harbored a microbiota composition that deviated from the microbiota of HC, which warrants further investigation.