IS GUT MICROBIOME DIVERSITY IMPORTANT AT IBD ONSET? A SYSTEMATIC REVIEW OF THE LITERATURE AND META-ANALYSIS OF ALPHA DIVERSITY DATA

Abstract

Introduction Disruption of the gut microbiome has been widely reported in inflammatory bowel disease (IBD), particularly reduced bacterial diversity. Determining the role of this in IBD onset is hampered by a paucity of studies in newly diagnosed disease. We present outputs from a systematic review of the microbiome in pre-treatment IBD.

Methods We searched MEDLINE, Embase between inception and December 2022 for any study presenting microbial analysis of patients diagnosed with IBD in the pre-treatment phase. All screening and extractions were done independently in duplicate. Data extracted included all measures of microbial diversity, the source of samples, any reported controls and clinical/patient parameters. Where appropriate, we performed random-effects meta-analysis of standardised mean difference, reporting 95% CI values and sub-grouped by type of IBD.

Results 10,805 abstracts were screened and 217 full texts reviewed. Ultimately, 92 studies were included. 22 studies based on high-throughput technologies presented alpha diversity indices from IBD and controls. 86% of these offered a Shannon index. This was therefore used for synthesis and included faecal samples from 405 IBD (116 mixed, 225 Crohn’s disease [CD], 64 Ulcerative colitis [UC]) and 324 healthy controls (HC); alongside mucosal biopsies from 171 CD with 172 symptomatic controls (SC) and 42 UC with 60 SC. 68% of studies were paediatric.

12 studies presented Shannon diversity from faeces vs HC cohorts. The studies were highly heterogenous. Nonetheless, alpha diversity was significantly lower in IBD, across both UC and CD. 7 studies presented Shannon diversity from mucosal biopsies vs SC cohorts. No papers presented mixed IBD, so subtypes were reviewed separately. Heterogeneity was lower across these studies but differences in diversity did not reach significance (see figure 1 ).

Conclusions In IBD, faecal bacterial alpha diversity is significantly reduced compared to healthy controls, but mucosal alpha diversity is not in comparison with symptomatic patients without IBD. Factors influencing the faecal stream, such as rapid transit and malabsorption may exaggerate the difference between IBD and healthy. The similarity between mucosal diversity in IBD and symptomatic controls bolsters the view that other factors must be present alongside microbiome disruption to precipitate IBD. These signals will be further explored using secondary analysis of available inception sequencing datasets.