Inflammatory Bowel Disease (IBD), encompassing ulcerative colitis (UC) and Crohn's disease (CD), is a chronic inflammatory condition of the gastrointestinal tract with a rising global burden. Traditional diagnostic methods like endoscopy are invasive and costly, underscoring the need for non-invasive biomarkers. Recent research highlights the gut microbiome's pivotal role in IBD pathogenesis, alongside metabolomic and immunological dysregulation. This review synthesizes current knowledge on these biomarkers, proposing an integrative model to enhance diagnosis, prognosis, and personalized treatment strategies.
Global Burden and Prevalence
The global prevalence of IBD has surged, with 4.9 million cases reported in 2019, driven by environmental, genetic, and lifestyle factors. Incidence rates for CD and UC have risen dramatically, with higher morbidity in older adults and individuals with familial predispositions. The economic burden is significant, particularly in regions like Europe and Iran, where treatment costs vary by disease severity and healthcare systems.
Factors Affecting IBD
IBD etiology involves a complex interplay of genetic susceptibility (e.g., HLA gene variants), environmental triggers (e.g., diet), and microbial dysbiosis. Polymorphisms in immune-related genes, such as TNFα and IL-1, exacerbate inflammation, while diet shapes microbiome composition. Notably, the NOD2 gene variant correlates with Enterobacteriaceae abundance, linking genetics to microbial imbalance.
Microbiome Signatures in IBD
The gut microbiome in IBD patients exhibits reduced alpha diversity and altered composition, marked by:
Bacteria: Decreased F. prausnitzii (butyrate producer) and increased Enterobacteriaceae (e.g., E. coli), contributing to inflammation.
Fungi: Elevated Candida albicans and Malassezia, which promote pro-inflammatory cytokines like IL-17.
Viruses: Enriched Caudovirales phages, associated with bacterial dysbiosis.
Extracellular vesicles (EVs) from gut microbiota and host cells modulate immune responses and serve as potential biomarkers, with miRNAs and proteins like ANXA1 linked to disease activity.
Metabolome Signatures in IBD
Dysbiosis disrupts metabolite profiles, including:
Short-chain fatty acids (SCFAs): Reduced butyrate levels impair anti-inflammatory responses.
Bile acids and TCA cycle intermediates: Altered in IBD, correlating with disease severity.
Metabolomic techniques (NMR, MS) reveal distinct fecal and serum profiles, aiding in differentiating CD from UC and predicting treatment responses.
Immunological Biomarkers
Key immune markers include:
Diagnosis: Anti-Saccharomyces cerevisiae antibodies (CD) and pANCA (UC).
Prognosis: Oncostatin M (OSM) predicts non-response to anti-TNF therapy.
Treatment Monitoring: Elevated IL-1β, IL-8, and CXCL chemokines during relapse.
Dysbiosis-driven metabolite changes (e.g., low SCFAs) exacerbate inflammation via NF-κB and NLRP3 pathways.
Integration of Biomarkers
An integrative model links microbiome shifts (e.g., F. prausnitzii decline) to reduced butyrate, disrupting Th17/Treg balance and elevating IL-6/IL-17. Such interactions highlight the potential for multi-omics approaches to unravel IBD mechanisms.
AI-ML Advancements
Machine learning algorithms analyze microbiome and metabolome data to predict disease flares and therapy responses. Challenges include dataset diversity and model generalizability, but AI holds promise for personalized IBD management.
Future Directions
Longitudinal studies and multi-omics integration are needed to validate biomarkers across diverse populations. Research should explore causal microbiome-immune relationships and therapeutic microbiome modulation.
Conclusions
This review underscores the interconnected roles of microbial, metabolic, and immune biomarkers in IBD. While current biomarkers lack universal specificity, integrative approaches and AI-driven analyses offer transformative potential for precision medicine in IBD care.
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The study was recently published in the Journal of Translational Gastroenterology .
Journal of Translational Gastroenterology (JTG) dedicates to improving clinical diagnosis and treatment, advancing understanding of the molecular mechanisms, and promoting translation from bench to bedside of gastrointestinal, hepatobiliary, and pancreatic diseases. The aim of JTG is to provide a forum for the exchange of ideas and concepts on basic, translational, and clinical aspects of gastroenterology, and promote cross-disciplinary research and collaboration.
