Metabolic Profiles May Predict IBD up to 10 Years Before Onset

Liam Davenport

March 04, 2025

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TOPLINE:

Scores on a broad panel of blood metabolomic markers may predict inflammatory bowel disease (IBD) up to 10 years before onset, indicated a new study that leveraged population data from three countries.

METHODOLOGY:

Using nuclear magnetic resonance, researchers measured 250 metabolic biomarkers in 490,000 people (aged 40–70 years) in the UK Biobank. At baseline, 6066 had IBD. During a follow-up of 10 years, 2522 developed IBD, allowing researchers to study the prediagnostic metabolic profile of IBD.
Logistic and proportional hazard regressions were used to investigate associations between individual metabolomic biomarkers and IBD, and least absolute shrinkage and selection operator regression was employed to build predictive models of future IBD onset.
The resulting predictive model was tested in the Estonian Biobank of 186,000 people (aged 18–100 years) and the THL Biobank, based in Finland, of 32,000 individuals (aged 25–98). The Estonian Biobank included 1675 IBD cases at baseline and 397 incident cases over 4 years of follow-up. The Finnish Biobank included 386 IBD cases at baseline and 160 incident cases over 8 years of follow-up.

TAKEAWAY:

The metabolite glycoprotein acetyls, a biomarker of systemic inflammation, was most strongly associated with the risk for prevalent and incident Crohn’s disease and ulcerative colitis, but almost all the metabolite classes included in the analysis were linked to the risk for IBD, with the effect larger in Crohn’s disease than in ulcerative colitis.
Combining metabolomic markers allowed the prediction of both Crohn’s disease and ulcerative colitis up to 10 years before onset, a finding that was replicated across all three biobanks.
Using 5-year follow-up data, the team calculated that their metabolomics multi-biomarker predicted the onset of Crohn’s disease at an area under the receiver operative characteristic curve (AUC) of 0.73 and the onset of ulcerative colitis at an AUC of 0.62.
Combining the metabolomics multi-biomarker with traditional predictors, such genetic risk score and C-reactive protein levels and other blood markers, did not markedly improve performance, and the combined markers only weakly predicted IBD progression (emergency admission, surgery, or death).

IN PRACTICE:

“Metabolomic changes proceed Crohn’s disease and ulcerative colitis as far as 10 years in advance,” the study presenter said. “The strongest signal is for inflammation,” but the changes are “systemic.”

Commenting, Ashwin Ananthakrishnan, MBBS, MPH, director, Crohn’s and Colitis Center, Massachusetts General Hospital, Boston, said: “This study is valuable in…demonstrating that this state extends up to 10 years prior to IBD diagnosis” and “provides a greater understanding of pathogenesis.”

SOURCE:

This study, by Aleksejs Sazonovs, PhD, Center for Molecular Prediction of Inflammatory Bowel Disease (PREDICT), Aalborg University Copenhagen, Copenhagen, Denmark, and colleagues, was presented at the European Crohn’s and Colitis Organisation (ECCO) 2025 Congress.

LIMITATIONS:

Sazonovs noted that the study is limited by the relatively older age of the participants in the UK Biobank than the general IBD population. Ananthakrishnan said that there are a number of limitations to the analysis, including the relatively homogeneous racial and ethnic makeup of the populations studied and their relatively homogeneous geography of origin, as well as the lack of information on other risk factors.

DISCLOSURES:

No funding was declared. Sazonovs declared no relevant financial relationships. Other authors are employees of Nightingale Health, whose nuclear magnetic resonance-based metabolomics assessment was used in the study, and some declared relationships with pharmaceutical companies.