TY - JOUR
T1 - The Gut Microbiome at the Onset of Inflammatory Bowel Disease
T2 - A Systematic Review and Unified Bioinformatic Synthesis
AU - Rimmer, Peter
AU - Zhang, Fan
AU - Scott, Gregor
AU - Kaakoush, Nadeem
AU - Lewindon, Peter
AU - Ashton, James
AU - Kansal, Shivani
AU - Van Limbergen, Johan
AU - Sigall-Boneh, Rotem
AU - Pai, Nikhil
AU - Croitoru, Ken
AU - Zhang, Ting
AU - Paljetak, Hana Čipčić
AU - Quraishi, Mohammed Nabil
AU - Hold, Georgina L.
AU - Gordon, Morris
AU - Iqbal, Tariq H.
AU - Hansen, Richard
N1 - Publisher Copyright:
© 2025 The Authors
PY - 2025/12/23
Y1 - 2025/12/23
N2 - 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.
AB - 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.
KW - Crohn's Disease
KW - Microbiota
KW - Treatment-Naïve
KW - Ulcerative Colitis
UR - https://www.scopus.com/pages/publications/105025545363
U2 - 10.1053/j.gastro.2025.09.014
DO - 10.1053/j.gastro.2025.09.014
M3 - Article
AN - SCOPUS:105025545363
SN - 0016-5085
JO - Gastroenterology
JF - Gastroenterology
ER -