IBD Inflammation Marker: The Case for Glycans

Glycans — complex sugars that coat every cell in the human body — are central regulators of immune function and inflammation, and their composition shifts measurably in inflammatory bowel disease (IBD). In IBD, which encompasses both Crohn's disease and ulcerative colitis, the immune system mounts a chronic, dysregulated inflammatory response in the gut. Glycans sit at the interface of that response: they determine whether antibodies activate or suppress inflammation, and their patterns change in ways that are detectable in the blood long before many clinical symptoms become apparent.

For a deeper grounding in how glycans work as biomarkers of immune aging and chronic inflammation, read Glycans: The Sugars That Reveal Your Biological Age and Immune Health.

What happens to IgG glycans in people with IBD?

In both Crohn's disease and ulcerative colitis, IgG glycosylation (the pattern of complex sugars attached to Immunoglobulin G antibodies) shifts toward a pro-inflammatory state. Specifically, galactosylated IgG structures decrease while agalactosylated species increase, pushing the immune profile in a direction associated with chronic inflammatory activity.

This matters because galactose and sialic acid on IgG glycans are what make an antibody anti-inflammatory. When an IgG glycan carries sialic acid at its tip, the antibody suppresses inflammation. When it lacks both sialic acid and galactose, the same molecule activates inflammation, in this case through the lectin pathway and complement activation. In IBD, the balance tips persistently toward the pro-inflammatory configuration.

A Scottish study examining IgG glycosylation in Crohn's disease (287 CD patients and 320 controls, average age 42) found a significant increase in G0 and B glycan traits and a decrease in G1, G2, and S glycan structures in CD patients compared to controls, with an AUC of 0.77 for predictive value. In the ulcerative colitis arm of the same research program (507 UC patients and 320 controls, average age 45) a significant increase in G0 and decrease in G1 was observed, with an AUC of 0.72.

"In many inflammatory diseases, IgG glycans change up to a decade before people receive a diagnosis. They are not only biomarkers that tell you what is going on — they are functional effectors that actively contribute to the progression of low-grade chronic inflammation."

— Prof. Gordan Lauc, Chief Scientific Officer, GlycanAge; Professor of Biochemistry and Molecular Biology, University of Zagreb

Does IBD accelerate biological aging?

IBD is associated with measurable biological age acceleration, detectable at the time of diagnosis and consistent across geographically distinct patient populations. In a multi-cohort study using GlycanAge to quantify biological age in treatment-naive IBD patients across the UK, US, Italy, and the Netherlands, IBD patients showed significantly higher GlycanAge acceleration than non-IBD individuals.

In Crohn's disease specifically, biological age ran substantially ahead of chronological age across all four cohorts. Because all patients were untreated at sampling, these findings reflect disease biology directly, not the downstream effects of medication. Machine learning models built on IgG glycan profiles achieved strong discriminatory performance across cohorts, age groups, and sexes.

The consistency of this pattern across four countries, detectable at diagnosis, in untreated patients, positions GlycanAge as a clinically relevant indicator of systemic inflammatory burden, rather than a wellness metric alone. As Prof. Gordan Lauc, Chief Scientific Officer of GlycanAge, has noted, the scale of glycomic data now available leaves little scientific justification for continuing to overlook glycans as biomarkers in clinical settings.

Can glycan biomarkers predict how a patient with IBD will respond to treatment?

Emerging research suggests that glycan composition in colonic mucosal biopsies has demonstrated prognostic value for predicting therapeutic response in IBD patients. Early-stage evidence indicates that the levels and composition of the mucosal glycome (detectable in tissue collected during colonoscopy) can predict failure to standard therapy and therefore eligibility for escalation to biologics.

Specifically, the expression levels of branched glycans in the colonic mucosa at inaugural diagnosis of ulcerative colitis predicted which patients would not respond to first-line anti-inflammatory agents and would require more aggressive immunomodulatory therapy. This has direct implications for clinical decision-making: rather than following a step-by-step escalation that exposes patients to ineffective treatments and prolonged suffering, glycan profiling could support earlier, more targeted therapeutic decisions.

"The composition of the mucosal glycome — detectable in a biopsy collected during colonoscopy — has real prognostic value. We found that the expression of branched glycans in the colonic mucosa at inaugural diagnosis of ulcerative colitis can predict failure to standard therapy, and therefore eligibility to escalate to more aggressive treatment such as biologics. The way the mucosal glycome is composed can inform clinicians on whether early, aggressive immunotherapy is preferable to the conventional step-by-step escalation approach."

— Prof. Salomé Pinho, Glycan Trigger Project Coordinator; i3S, University of Porto

For functional medicine practitioners, this positions mucosal glycan analysis as a potential future addition to the IBD clinical algorithm, not as a replacement for colonoscopy, but as a layer of biological information that colonoscopy already makes accessible.

GlycanAge is not a diagnostic tool and does not serve as a disease predictor or risk score. Glycan insights reflect the similarities of an individual's profile with patterns observed across disease populations, and are designed to be interpreted alongside clinical history and other health data.

How does IBD-related glycan alteration connect to the gut microbiota?

Glycan composition at the intestinal mucosa influences microbiota composition, and disruption of that glycan layer may be an early trigger in the transition from gut health to chronic intestinal inflammation. The EU-funded Glycan Trigger project, coordinated by the University of Portugal, is investigating precisely this mechanism: how mucosal glycosylation and the glycocalyx (the glycan coat on intestinal epithelial cells) act as a master trigger for the shift from health to IBD.

The working hypothesis, supported by existing evidence, is that changes in mucosal glycosylation activate pro-inflammatory immunological players, alter the microbial environment, and initiate the cascade that leads to chronic intestinal inflammation. In ulcerative colitis models, a deficiency in a specific glycan structure on CD3-positive T lymphocytes infiltrating the intestinal mucosa was found to drive a hyperactive immune response associated with disease severity, and restoring that glycosylation profile achieved immune control and had downstream effects on microbiota composition.

Is inflammaging in IBD inevitable, or can it be modified?

Chronic inflammation, including the accelerated immune aging seen in IBD, is not a fixed biological destiny. Research published in Nature Aging in 2025 challenges the assumption that inflammaging is a universal feature of aging, showing that age-related inflammatory markers are prominent in industrialised populations but minimal or absent in non-industrialised groups. This reframes chronic inflammation as a modifiable, environment-driven process rather than an inevitable consequence of time.

For IBD patients, this is clinically meaningful: the inflammatory burden measurable through IgG glycans is not static. Glycans are responsive to lifestyle interventions, pharmacotherapy, and other biological changes. In a longitudinal study tracking participants over two decades, glycan profiles became progressively more anti-inflammatory as participants lost weight, demonstrating that the glycan signal responds to real biological change. For IBD patients managing their condition through diet, medication, or other interventions, GlycanAge provides a way to track whether those interventions are shifting the underlying inflammatory biology.

"You can change your glycans through lifestyle interventions and, in some cases, pharmacological ones. By doing so, you make your immunoglobulins less pro-inflammatory — and that reduction in low-grade chronic inflammation is what we hope will postpone disease. Glycans can serve as intermediate endpoints: early signals you can measure to assess whether an intervention is genuinely moving someone in the right direction."

— Prof. Gordan Lauc, Chief Scientific Officer, GlycanAge; Professor of Biochemistry and Molecular Biology, University of Zagreb

How is GlycanAge different from standard IBD inflammation markers like CRP or ESR?

Standard inflammation markers, such as CRP, ESR, TNF-alpha, measure acute inflammation, not the chronic, low-grade inflammatory burden that drives biological aging and long-term disease progression. These markers change close to disease events and are heavily skewed by acute inflammatory activity, making them poor signals for the kind of sustained, subclinical inflammation that characterises IBD between flares.

GlycanAge measures IgG glycosylation, which is a stable, integrative signal that reflects the cumulative inflammatory state of the immune system rather than its acute response at a single moment. Where CRP can fluctuate hourly, glycan profiles are stable enough to filter biological noise while remaining responsive to genuine biological change over 3–6 months. For IBD patients and their clinicians, this means GlycanAge can track the trajectory of immune aging across the disease course, not just flag an active flare.

GlycanAge is not a diagnostic tool and does not serve as a disease predictor or risk score. Glycan insights reflect the similarities of an individual's profile with patterns observed across disease populations, and are designed to be interpreted alongside clinical history and other health data.

How often should someone with IBD retest with GlycanAge?

Meaningful changes in IgG glycan profiles become detectable within 3–6 months of a targeted intervention, whether that is a dietary change, a new medication, or a structured lifestyle modification. For IBD patients, a practical approach is to establish a biological age baseline at diagnosis or at the start of a new treatment protocol, then retest at 6 months to assess whether the intervention is shifting the inflammatory profile in the right direction.

Across repeat testers in the GlycanAge database, the average biological age reduction is 6 years. This shows evidence that the marker responds meaningfully when health genuinely changes. For clinicians managing IBD patients, this retest cadence creates an objective, longitudinal record of immune aging that complements standard clinical monitoring and supports more informed therapeutic decisions.

If you are managing IBD, working with patients who have chronic gut inflammation, or integrating biological age testing into a functional medicine practice, GlycanAge provides the inflammatory biomarker that standard panels tend to miss.

Order a test kit or explore how GlycanAge fits into your clinical workflow.

For practitioners looking to integrate GlycanAge into IBD monitoring and chronic inflammation protocols, visit the Healthcare Providers page.

External Sources

• https://academic.oup.com/ibdjournal/article/21/6/1237/4579323 — Trbojevic Akmacic I, Ventham NT, Theodoratou E, et al. Inflammatory bowel disease associates with proinflammatory potential of the immunoglobulin G glycome. Inflammatory Bowel Diseases. 2015;21(6):1237–1247.

• https://www.nature.com/articles/s43587-025-00888-0 — Franck M, Tanner KT, Tennyson RL, et al. Nonuniversality of inflammaging across human populations. Nature Aging. 2025;5(8):1471–1480. Published June 30, 2025.

• https://glycantrigger.eu/ — GlycanTrigger Project. EU Horizon Europe Research and Innovation Actions, Grant Agreement No. 101093997. Coordinated by i3S, University of Porto, Portugal. Launched January 2023.