P1324 Longitudinal Changes in Gut Microbiota During the First Year following diagnosis of Inflammatory Bowel Disease – the IBSEN III study
Authors: Maseng M G , Hansen S H , Bang C , Valeur J , Huppertz-Hauss G , Opheim R , Perminow G , Boyar Cetinkaya R , Detlie T E , Kristensen V A , Asak Ø , Bengtson M B , Hovde Ø , Strande V , Vatn S , Aabrekk T B , Høivik M L , Hov J R ,   IBSEN III study group
Published: January 2025

Background

Despite the well-established involvement of the gut microbiota in inflammatory bowel disease (IBD), little is known about how the gut microbiota changes over time or how it varies with clinical disease activity and faecal calprotectin. To address this gap, we utilized the population-based inception cohort IBSEN III.

Methods

Stool samples from IBD patients and symptomatic controls (SC) were collected at diagnosis and after 3, 6, and 12 months. Comprehensive data collection was performed at baseline and the 12-month follow-up, while faecal calprotectin (f-calprotectin) and patient-reported clinical disease activity data were also gathered at 3 and 6 months. Stool microbiota profiling was performed targeting the V3-V4 region of the 16S rRNA gene, and a consensus-based approach utilizing mixed models was employed for the microbiota analysis.

Results

We included 761 subjects (median age 37, 48 % female) with ulcerative colitis (UC) and 448 subjects (median age 33, 55% female) with Crohn’ s disease (CD) who contributed at least one faecal sample, and respectively 79 and 58 provided samples at all four time points. A smaller proportion of our IBD population donated treatment naïve faecal samples (11% UC, 26% CD).

In the IBD population, the patient-reported disease activity decreased over time, as did F-calprotectin levels (mixed model p &lt; 0.001, median CD from 241 to 128, UC from 188 to 77). We used different thresholds of F-calprotectin for defining remission (50,150 and 250) and observed significant within-diagnosis differences (microbial diversity and consensus-based differential abundance analysis) depending on F-calprotectin status. Comparing F-calprotectin-defined inactive IBD (50,150 and 250) to symptomatic controls, there were significant differences between microbiota profiles from UC remission, but few/no differences to CD microbiota.

Distinct changes in the gut microbiota of IBD subjects were observed throughout the first year, such as increased alpha diversity (Shannon, mixed model p &lt; 0.001) and significant taxonomic changes (consensus-based differential abundance analysis, figure). There was a significant overlap between microbial patterns associated with F-calprotectin and patient-reported disease activity score (Fisher Exact test p &lt; 0.001), and the changes in these scores were reflected in the microbial changes over time (Fisher Exact test p &lt; 0.05). Significant changes comparing microbiota profiles in treatment naïve to post-treatment samples were found, both among subjects with CD and UC (consensus-based differential abundance analysis).

Conclusion

The gut microbiota during the first year after IBD diagnosis showed changes that paralleled inflammation and clinical disease activity.