Authors: Čipčić Paljetak H, Barešić A, Panek M, Perić M, Matijašić M, Lojkić I, Barišić A, Vranešić Bender D, Ljubas Kelečić D, Brinar M, Kalauz M, Miličević M, Grgić D, Turk N, Karas I, Čuković-Čavka S, Krznarić Ž, Verbanac D. Published in Gut Microbes, 2022. DOI: 10.1080/19490976.2022.2083419
Background & Rationale
Crohn’s disease (CD) and ulcerative colitis (UC), together forming inflammatory bowel disease (IBD), and irritable bowel syndrome (IBS) share overlapping symptoms but differ in pathology: IBD involves mucosal inflammation, while IBS is functional. Gut dysbiosis has been implicated in IBD, but most evidence comes from treated patients, where medication can independently alter microbiota. This study aimed to characterise mucosal and fecal microbiota in newly diagnosed, treatment-naïve patients across multiple gut locations, separating disease-related signatures from treatment effects, and comparing IBD-associated dysbiosis with that of IBS.
Study Design
This prospective, single-centre, observational case-control study enrolled treatment-naïve adults with CD, UC, or IBS, plus healthy controls (HC). Colonoscopy with mucosal biopsies from multiple gastrointestinal sites, alongside fecal sampling, was performed, and microbiota were characterised via 16S rRNA sequencing. The primary aim was comparing mucosal and fecal composition and diversity across groups; secondary aims covered regional mucosal variation and associations with clinical/endoscopic features. Blinding was not applicable. Analysis included alpha/beta diversity metrics and differential abundance testing.
Patient Population
Adults newly diagnosed with CD, UC, or IBS, untreated at enrolment, were compared with healthy controls. Baseline demographics and, for CD/UC, disease activity measures were reported by group. Sample availability varied somewhat by anatomical site and patient group.
Key Findings
Microbial diversity was reduced in CD and UC versus HC and IBS, in both mucosal and fecal samples; IBS diversity resembled HC. IBD patients, especially those with CD, showed reduced short-chain fatty acid-producing taxa (Ruminococcaceae, Faecalibacterium) and increased Proteobacteria, particularly Enterobacteriaceae, versus HC, with more pronounced shifts in CD than UC. HC mucosa showed distinct microbial profiles across gut sites; this regional distinctiveness was diminished in IBD, whose mucosal communities appeared more homogeneous along the tract. Fecal changes in IBD paralleled mucosal findings but were less pronounced. IBS composition more closely resembled HC than either IBD group, though some distinguishing features versus HC were noted. Non-significant comparisons were reported as null findings rather than inferred.
Discussion
Dysbiosis present in treatment-naïve CD and UC patients suggests microbial alterations arise early in disease, before pharmacological intervention, rather than resulting solely from treatment. Loss of regional mucosal distinctiveness in IBD, preserved in HC, is highlighted as a key structural feature of IBD dysbiosis. The similarity between IBS and HC microbiota supports a distinction between organic inflammatory disease and functional disorder despite symptom overlap. As a non-interventional sampling study using standard colonoscopy and biopsy, no treatment-related adverse events applied, and no procedural complications were reported.
Authors’ Conclusions
Treatment-naïve CD and UC patients show distinct mucosal and fecal dysbiosis versus HC and IBS, marked by reduced diversity, depleted SCFA-producing taxa, expanded Proteobacteria, and loss of regional mucosal heterogeneity. IBS microbiota more closely resembles healthy individuals. Limitations include single-centre design, sample size constraints across compartments and sites, and cross-sectional design precluding causal conclusions.
Reference
Čipčić Paljetak H, Barešić A, Panek M, Perić M, Matijašić M, Lojkić I, Barišić A, Vranešić Bender D, Ljubas Kelečić D, Brinar M, Kalauz M, Miličević M, Grgić D, Turk N, Karas I, Čuković-Čavka S, Krznarić Ž, Verbanac D. Gut microbiota in mucosa and feces of newly diagnosed, treatment-naïve adult inflammatory bowel disease and irritable bowel syndrome patients. Gut Microbes. 2022;14(1):2083419. doi:10.1080/19490976.2022.2083419.
This Scientific Publication Summary is an objective summary of the published trial for personal and educational use. It does not constitute clinical advice, endorsement of the intervention, or a recommendation to alter clinical practice.