The gut microbiome at the onset of inflammatory bowel disease: a systematic review and unified bioinformatic synthesis
Rimmer, Peter Zhang, Fan Scott, Gregor Hold, Georgina L Gordon, Morris Iqbal, Tariq H Hansen, Richard
Rimmer, Peter
Zhang, Fan
Scott, Gregor
Hold, Georgina L
Gordon, Morris
Iqbal, Tariq H
Hansen, Richard
Affiliation
University of Birmingham; University Hospitals Birmingham NHS Foundation Trust; University of New South Wales; NHS Greater Glasgow and Clyde; University of Sydney; University of Queensland; University of Southampton; Western Children's Health Centre; Centrum Unverstieit van Amsterdam; Edith Wolfson Medical Centre; University of Amsterdam; University of Pennsylvania; McMaster University; Mount Sinai Hospital; Shanghai Children's Hospital; University of Zagreb; Sheikh Shakhbout Medical City; University of Central Lancashire; University of Dundee
Other Contributors
Kaakoush, Nadeem
Lewindon, Peter
Ashton, James
Kansal, Shivani
Van Limbergen, Johan
Sigall-Boneh, Rotem
Pail, Nikhil
Croitoru, Ken
Zhang, Ting
Paljetak, Hana Cipcic
Quraishi, Mohammed Nabil
Lewindon, Peter
Ashton, James
Kansal, Shivani
Van Limbergen, Johan
Sigall-Boneh, Rotem
Pail, Nikhil
Croitoru, Ken
Zhang, Ting
Paljetak, Hana Cipcic
Quraishi, Mohammed Nabil
Publication date
2025-12-23
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Abstract
Background & aims: Few studies describe gut microbiome signatures in treatment-naïve new-onset inflammatory bowel disease (IBD). We present a novel secondary bioinformatic reanalysis of sequence outputs mapped to the latest microbial taxonomy.
Methods: MEDLINE and Embase searches were performed for microbiome studies in treatment-naïve IBD. Appraisal was completed with Risk Of Bias In Non-randomized Studies - of Exposures (ROBINS-E). Available 16S ribosomal RNA sequence data sets were downloaded and missing data sets requested. Integrated data were run through a unified QIIME2 bioinformatics pipeline. Multivariable models adjusting for methodologic differences were developed using MaAsLin2.
Results: There were 36 eligible studies; 18 contributed to bioinformatic reanalysis and 24 to supplementary meta-analysis. Samples from 1743 patients were included, comprising 678 from individuals with Crohn's disease (CD), 399 with ulcerative colitis (UC), 130 healthy controls (HCs), and 405 symptomatic controls (SCs); 990 of which were biopsy samples. Alpha diversity was reduced: feces-pediatric UC vs SCs, adult CD and UC vs HCs, and pediatric SCs vs HCs; pediatric biopsy samples-CD vs SCs, CD vs UC, and UC vs SCs. Beta diversity demonstrated clear distinctions between fecal and mucosal biopsy communities, least evident in UC, in addition to community separation by geography. Multivariate modeling revealed depletion of anaerobic and enrichment of aerobic and facultative anaerobic bacteria, alongside enrichment of oral genera across both CD and UC.
Conclusions: Core microbial perturbations at onset of CD and UC are depletion of anaerobes and enrichment of oxygen-tolerant, orally associated bacteria. As we place greater emphasis on early diagnosis and prediction of IBD risk, this finding may support innovative diagnostic approaches. Microbiome-targeted intervention and alteration of luminal oxygen availability may offer novel therapeutic avenues for new-onset patients and identified high-risk groups.
Citation
Peter Rimmer, Zhang F, Scott G; Microbiome Data Provision Group; Hold GL, Gordon M, Iqbal TH, Hansen R. The Gut Microbiome at the Onset of Inflammatory Bowel Disease: A Systematic Review and Unified Bioinformatic Synthesis. Gastroenterology. 2025 Dec 23:S0016-5085(25)06015-9. doi: 10.1053/j.gastro.2025.09.014. Epub ahead of print.
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Article