P1345 Association of gut microbiota changes and disease activity in patients with Crohn’s disease and ulcerative colitis: baseline data from the Australian IBD Microbiome study
Authors: Little R , Jayawardana T , Zhang F , Houshyar Y , Koentgen S , Wu N , Ellepola A , Tavakoli P , Chung A , Ho A , Read S , Boussioutas A , Ward M , Sparrow M , Gibson P , Ghaly S , Corte C , Talley N , Leach S , Lemberg D , Dutt S , Paramsothy S , Leong R , Connor S , Hold G 
Published: January 2025

Abstract

Background
Identifying microbial changes associated with active inflammation and inflammatory bowel disease (IBD) phenotype may improve understanding of drivers of disease activity1. This study aimed to characterise differences in gut microbial signatures according to inflammatory activity amongst patients enrolled in the Australian IBD Microbiome (AIM) study2.

Methods
Paired faecal and oral samples alongside participant and disease characteristics were collected at baseline from all patients with Crohn’s disease (CD) and ulcerative colitis (UC) enrolled in the AIM study from June 2019 to November 2023. Clinically active disease was defined as Crohn’s disease activity index (CDAI) score &gt;150 or partial Mayo score &gt;1. Biochemical activity was defined as faecal calprotectin (FCP) ≥150 μg/g. Faecal and oral microbial samples were collected in DNA stabilising buffer and stored at -80oC. Samples underwent 16S rRNA sequencing with annotation of DNA sequences to operational taxonomic units at the genus level. Differences in alpha diversity (Shannon index) and relative abundance of identified genera between the groups were assessed using Mann-Whitney U tests. Beta diversity (Bray-Curtis dissimilarity) between bacterial communities were shown using the Principal Coordinate Analysis (PCoA), and significance of variance tested using ADONIS within R.

Results
446 participants (232 CD, 214 UC) returned baseline faecal (n = 403) and/or oral samples (n = 436). The majority of patients were in clinical and biochemical remission with patient and disease characteristics presented in Table 1. Oral and faecal microbial analyses showed no statistical differences in alpha or beta diversity between CD and UC patients with clinical or biochemical activity vs. those in remission. In CD, lower faecal alpha diversity was observed in patients with a stricturing phenotype (p = 0.017) and isolated ileal disease (p = 0.043) in comparison to an inflammatory phenotype and colonic CD, respectively. No differences were observed according to UC extent. There were 17 and 39 genera with significantly different relative abundances between FCP activity vs. FCP remission in CD and UC patients, respectively (Figure 1).

Conclusion
There were no differences in broad measures of oral or faecal microbial community structure between IBD patients in clinical or biochemical remission compared to those with active disease. However, relative abundances at the genus-level distinguished IBD patients according to biochemical activity. Increasing the sequencing depth, as well as analysing serial biological sampling and their relationship to longitudinal changes in disease activity may allow identification of microbial signatures associated with both flare and pre-flare states.

References
1. Little RD, Jayawardana T, Koentgen S, et al. Pathogenesis and precision medicine for predicting response in inflammatory bowel disease: advances and future directions. eGastroenterology 2024;2:e100006. doi:10.1136/ egastro-2023-100006
2. Williams A, Paramsothy R, Wu N, et al. Australia IBD Microbiome (AIM) Study: protocol for a multicentre longitudinal prospective cohort study. BMJ Open 2021;11:e042493. doi: 10.1136/bmjopen-2020-042493