P1340 Gut microbiota changes are associated with type of advanced therapy in patients with Inflammatory Bowel Disease: baseline data from the Australian IBD Microbiome study
Authors: Little R , Jayawardana T , Zhang F , Koentgen S , Wu N , 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
Gut microbiota are associated with both disease course and treatment outcomes in inflammatory bowel disease (IBD)1. This study aimed to characterise differences in gut microbial signatures according to medication use in the Australian IBD Microbiome (AIM) study2.

Methods
Faecal and oral samples alongside participant characteristics were collected at baseline from all patients with IBD enrolled in the AIM study from June 2019 to November 2023. Faecal and oral microbial samples were collected in DNA stabilising buffer, aliquoted 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 observed genera between medication groups were assessed using Mann-Whitney U and Kruskal-Wallis 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) with patient and disease characteristics presented in Table 1. No differences in faecal calprotectin were observed between patients on advanced therapy vs. patients who were not, nor between each advanced therapy class. Patients on advanced therapy had lower alpha diversity (p = 0.003) and distinct beta diversity (R2 0.64, p = 0.002) than those not on advanced therapy. Patients on anti-TNF therapy had lower alpha (p &lt; 0.001) and distinct beta diversity (R2 1.75, p = 0.008) compared to patients on no advanced therapy (Figure 1AB). Alpha diversity remained lower when comparing those on either infliximab (p = 0.008) or adalimumab (p = 0.012) to patients on no therapy. There were no differences in alpha or beta diversity between other advanced therapy classes, between types of immunomodulator and between patients on 5-ASA compared to patients who were not. Pairwise comparisons between patients on no therapy and each class of advanced therapy demonstrated significantly different relative abundances of multiple genera observed in faecal samples (Figure 1C). No differences were observed in oral samples.

Conclusion
Distinct differences in both community structure and the relative abundance of multiple genera were observed in IBD patients according to type of advanced therapy despite no significant difference in biochemical activity. No microbiota differences were observed according to conventional 5-ASA or immunomodulator use. Future analysis including longitudinal samples and treatment outcomes may allow identification of unique microbial signatures predictive of treatment response.

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