From Treatment to Prevention in IBD - Gastroenterology Feb.26

Introduction

Inflammatory bowel disease (IBD) is no longer a condition confined to Western countries. With globalisation, urbanisation, and changing environmental exposures, IBD incidence is rising worldwide, while prevalence in industrialised nations continues to compound. If current trends persist, IBD prevalence may exceed 1% of the population in several countries within the next decade.

This consensus-driven paper argues that even modest reductions in incidence could meaningfully reverse long-term prevalence, and that the time has come to shift the IBD paradigm—from reacting to established disease to predicting and preventing it.

Why prevention is now realistic

Accumulating evidence shows that Crohn’s disease (CD) has a long preclinical phase, marked by:

immune activation,

gut barrier dysfunction,

microbiome alterations,

and circulating biomarkers are detectable years before symptoms.

These insights mirror earlier breakthroughs in type 1 diabetes, where defining preclinical stages enabled the first approved preventive therapy. The authors argue that IBD is now at a similar inflexion point.

The role of the PROMISE Consortium

To accelerate progress, PROMISE integrates:

prospective cohorts of asymptomatic first-degree relatives (FDRs),

large prediagnostic biobanks,

and multiomics platforms (genomics, proteomics, microbiome, immune profiling).

The goal is not a single biomarker, but integrated risk models that identify individuals most likely to progress to clinical disease—creating a rational entry point for prevention trials.

Key challenges that must be solved

The workshop identified several critical gaps:

1) Low positive predictive value (PPV)

Even strong biomarkers struggle with PPV because IBD prevalence is low. Defining what level of risk justifies intervention—ethically and clinically—remains unresolved.

2) Lack of a preclinical staging system

Unlike type 1 diabetes, IBD lacks clearly defined stages before diagnosis. Without staging, it is difficult to time interventions or define trial endpoints.

3) Biological heterogeneity

Preclinical pathways may differ by phenotype (ileal vs colonic CD, complicated vs inflammatory disease), demanding phenotype-specific biomarkers.

4) Limited scalable screening tools

Most current biomarkers are research-grade. Clinically deployable, reproducible, noninvasive assays are urgently needed.

What patients and families think

Importantly, patients and unaffected relatives are not resistant to prevention:

Most are willing to undergo risk testing, especially blood- or stool-based.

Lifestyle-based interventions (diet, exercise, smoking avoidance) are widely acceptable.

Acceptance of drug-based prevention depends on perceived risk and benefit.

This underscores the need for risk counselling, shared decision-making, and close partnership with patient advocacy groups.

A prevention framework for IBD

The authors outline a risk-based prevention strategy:

Population-level (primordial prevention):

Healthy diet, physical activity, smoking avoidance, and reduced antibiotic exposure.

High-risk individuals (primary prevention):

Targeted lifestyle and dietary interventions in FDRs or genetically susceptible individuals.

Preclinical disease (secondary prevention):

Trials testing whether immune- or microbiome-targeted therapies can delay or prevent disease onset.

Several dietary, microbial, and biologic interception trials are already underway.

Call to action

The paper concludes with a strong, unified message:

Prediction and prevention of IBD will not happen without global coordination.

Priorities include:

integrating preclinical cohorts worldwide,

standardising biomarker platforms,

establishing high-risk clinics,

designing ethically sound prevention trials,

and embedding patients and families at every stage.

Bottom-line takeaway:

IBD is no longer a disease we must wait to diagnose. With emerging biomarkers, longitudinal cohorts, and lessons from other immune-mediated diseases, prediction and prevention are now scientifically plausible. What’s needed next is coordinated investment, consensus, and courage to rethink how—and when—we intervene.

One-line GastroAGI takeaway:

The future of IBD care may begin years before symptoms—if we choose to act.