Global study reveals gut bacteria changes at the earliest stages of inflammatory bowel disease

Patients experience significant changes in gut bacteria at the onset of inflammatory bowel disease (IBD), a new international study has found - offering new hope for earlier diagnosis and future treatments.

Published in Gastroenterology, the study is the first to combine raw microbiome data from multiple studies. The team analysed data from more than 1,700 children and adults across 11 countries who have been recently diagnosed and before starting any treatment.

The findings reveal that people newly diagnosed with the most common IBD subtypes, Crohn’s disease and ulcerative colitis, lose beneficial anaerobic bacteria that help with digestion of complex carbohydrates. Patients instead experience a rise in oxygen-tolerant bacteria from the mouth that travel in the gut.

“These findings are incredibly important as our research captured as much data from as many studies as possible,” said Dr Richard Hansen from Dundee’s School of Medicine and joint-lead author of the study.

“What surprised us was that almost all the bacteria significantly reduced in IBD at the onset of the disease were anaerobes, meaning they thrive in oxygen-free environments and are sensitive to the presence of oxygen. This brings a renewed focus on the importance of oxygen in changing the IBD microbiome and could potentially offer new opportunities for detecting, treating and perhaps even avoiding IBD. 

“The second important finding we identified was that many of the bacteria that significantly increased were usually associated with the mouth. This potentially means that whatever changes in the microbiome when IBD occurs drives out anaerobes and encourages oral bacteria instead.”

Dr Peter Rimmer from the University of Birmingham and Consultant Gastroenterologist at University Hospitals Birmingham NHS Foundation Trust, and joint lead author of the study said, “While previous research has suggested that a shift toward oxygen-tolerant bacteria and a loss of beneficial anaerobes may be involved in IBD, this is the first study to demonstrate these changes so clearly at the onset of disease - and across multiple international datasets.

“This research gives us a clearer picture of what’s happening in the gut at the very start of IBD. Our findings suggest that changes in gut oxygen levels and the migration of bacteria from the mouth to the gut may play a key role in triggering inflammation – and these patterns could pave the way for earlier diagnosis and new treatments for IBD patients.”

“The study supports the ‘oxygen hypothesis’, the idea that increased oxygen in the gut lining may disrupt the delicate balance of the microbiome, contributing to disease. It also highlights the presence of oral bacteria such as Granulicatella and Haemophilus in the gut, which may offer new targets for treatment or prevention.

Professor Morris Gordon, Co-director of the Biomedical Evidence Synthesis and Translation to practice (BEST) unit and Professor of Evidence Synthesis and Systematic Review at the University of Lancashire added, “This unique study combined significant clinical, scientific and evidence synthesis expertise to identify the unique conditions in the gut at the time of diagnosing this condition. This opens up avenues to investigate regarding screening, diagnosis and therapies.”

These findings could support the development of innovative diagnostic tools for earlier detection of IBD and point to promising new treatment strategies that target the microbiome or modify oxygen levels in the gut, particularly for newly diagnosed patients and those at high risk.

Professor Tariq Iqbal, joint senior author of the study, Director of the University of Birmingham’s Microbiome Treatment Centre, and theme lead for the NIHR Birmingham Biomedical Research Centre’s Oral, Intestinal and Systemic Health research theme said, “This study demonstrates the value of collaborative research in the microbiome field. By combining global data and advanced bioinformatics, we’re moving closer to personalised, non-drug therapies that could transform how we treat chronic gut conditions like IBD.”

The project was delivered through the National Institute for Health and Care Research (NIHR) Birmingham Biomedical Research Centre and collaborators from University of Lancashire, the University of New South Wales (Australia), NHS Greater Glasgow and Clyde, and the University of Dundee.

The NIHR Birmingham Biomedical Research Centre is funded to improve outcomes for people with inflammatory conditions, and among the research themes is a focus on oral, intestinal and systematic health.

The Gut Microbiome at the Onset of Inflammatory Bowel Disease: A Systematic Review and Unified Bioinformatic Synthesis, is available to download.