Can Doctors Predict Which Children With Crohn’s Disease Will Respond to Food-Based Therapy?

For children diagnosed with Crohn’s disease, one of the most striking paradoxes in modern medicine involves the humblest of treatments: food. Exclusive enteral nutrition, in which a child consumes nothing but a nutritionally complete liquid formula for several weeks, can induce remission as effectively as powerful immunosuppressive drugs, and it does so without the infection risks, growth suppression and malignancy concerns that shadow biologic therapies. Yet the treatment remains stubbornly unpredictable. Some children achieve deep, durable remission; others complete the full course with little improvement. A newly published narrative review in Pediatric Research by Paulina Krawiec of the Medical University of Lublin and Lissy de Ridder of Erasmus MC Sophia Children’s Hospital and Leiden University Medical Center takes stock of what clinicians actually know about predicting which young patients will benefit, and the answer is both encouraging and sobering.

The scale of the problem is growing. Pediatric-onset inflammatory bowel disease is rising in incidence worldwide, and children tend to carry a more aggressive disease phenotype than adults, facing decades of potential inflammation, hospitalization and surgery. Biologic agents such as infliximab and adalimumab have transformed outcomes, but long-term cohort data show that a substantial fraction of children lose response over time, and drug approval pathways for young patients remain constrained. Against this backdrop, nutritional therapy occupies a unique position: it is the only induction strategy recommended by European guidelines as first-line for pediatric Crohn’s disease that simultaneously improves inflammation, supports growth and avoids pharmacological side effects. The catch, as the review emphasizes, is that remission rates vary considerably across studies depending on research design, treatment population and how remission is defined in the first place.

The authors frame the field’s central challenge as a transition away from a one-treatment-suits-all strategy toward a tailor-made, precision-based approach. In principle, a clinician armed with a reliable treatment-responsiveness phenotype could match each child to the therapy most likely to work before the first formula feed or the first injection. The benefits would cascade through the healthcare system: fewer months spent on ineffective regimens, less exposure to unnecessary immunosuppression, earlier escalation for the children who need it, and reduced lifetime costs of a disease whose economic burden is among the highest of any chronic inflammatory condition. The obstacle is that, despite decades of research, the evidence base for definitive predictors of response to nutritional therapy remains insufficient, a conclusion the review states plainly rather than glossing over.

What does the existing evidence actually suggest? Among the most consistently reported signals are early clinical improvement and a reduction in faecal calprotectin, the stool-based marker of intestinal inflammation that has become a workhorse of pediatric IBD monitoring. Serial measurements during exclusive enteral nutrition have been shown to track with disease activity and treatment response, and falling calprotectin concentrations during therapy have been linked to better outcomes and to the prediction of clinical relapse after treatment ends. Early mucosal healing, visible at endoscopy in newly diagnosed children, is also associated with improved long-term outcomes. But the picture is not clean: at least one prospective pediatric study concluded that faecal calprotectin is not a clinically useful marker for predicting early non-response to exclusive enteral nutrition, and the review notes that the rapid fall in calprotectin seen during treatment is lost quickly once food is reintroduced. Timing, it seems, matters as much as the marker itself.

Disease location offers another thread of evidence, though a tangled one. Classic work from the early 2000s suggested that colonic Crohn’s disease without ileal involvement responds less well to enteral nutrition, hinting that the intestinal segment where inflammation resides shapes the therapy’s effectiveness. Later studies complicated this view, with some reporting that disease phenotype does not influence clinical remission at all, and others examining whether specific scoring systems can predict short- and long-term mucosal healing across different gastrointestinal segments. The review also highlights practical determinants that have nothing to do with biology: adherence. Real-world studies of children starting exclusive enteral nutrition have identified factors associated with higher adherence and better response, and parent-perspective research underscores how difficult the diet’s social and psychological demands can be for families. Whether the formula is polymeric or elemental, and whether it is delivered orally or by tube, appears to have little effect on outcomes, which at least simplifies one clinical decision.

The most scientifically vibrant frontier, and the one the review treats as the field’s future horizon, lies in the gut microbiome. Nutritional therapy works, at least in part, by reshaping the microbial communities that drive intestinal inflammation, and several prospective studies have now reported microbial signatures that predict response. Children whose baseline gut communities contain particular bacterial taxa and functional profiles have been shown more likely to achieve sustained remission after exclusive enteral nutrition, and early shifts in microbial community structure during treatment have been associated with durable remission. Metabolomic analyses add another layer, with gut metabolome signatures alongside microbiota profiles predicting response in prospective pediatric cohorts. Even a child’s pre-diagnosis diet has been found to correlate with the microbiome and to predict response to enteral nutrition, suggesting that long-term dietary habits may prime the gut environment for success or failure before therapy even begins.

These findings align with a broader conceptual shift captured in a 2024 position paper from the European Society for Paediatric Gastroenterology, Hepatology and Nutrition, which called for precision nutrition in pediatric IBD. The logic is compelling: if exclusive enteral nutrition remodels the microbiome and its metabolic output, then the composition of a child’s starting microbial community should, in theory, determine how far that remodeling can go. Multidisciplinary consensus work on microbiome-based biomarkers published in The Lancet Microbe has begun to define the standards such biomarkers would need to meet before clinical deployment, and the review argues that integrating clinical data with multiomic information, spanning genomics, microbiomics and metabolomics, into a unified decision-making framework could eventually enable genuinely personalized treatment selection. Machine learning approaches developed for targeted therapies elsewhere in medicine offer a template for how such heterogeneous data streams might be combined.

The authors are careful, however, to temper enthusiasm with rigor. Anticipating treatment response, they write, transcends simple stratification based on clinical characteristics, meaning that no checklist of age, disease location, severity or laboratory values currently suffices to forecast outcome. The literature they surveyed provides insufficient evidence for definitive predictors, and many of the most promising microbiome and metabolome studies are small, single-center and retrospective, vulnerable to the confounding and overfitting that plague biomarker research. The path forward, they suggest, involves prospective validation of candidate predictors in large, well-phenotyped cohorts, harmonized definitions of remission and response, and ultimately the kind of integration of clinical and multiomic data that precision medicine initiatives in other fields have begun to demonstrate at scale.

For families facing a new diagnosis, the practical message of the review is one of cautious optimism. Nutritional therapy remains a first-line, evidence-based option, whether as exclusive enteral nutrition or as partial enteral nutrition combined with the Crohn’s disease exclusion diet, and randomized trial evidence shows the dietary approach can induce rapid, sustained remission in children. Early clinical improvement and falling faecal calprotectin during the first weeks of treatment are reasonable indicators that the therapy is working, and clinicians can use them to guide decisions about continuing or switching. What the field cannot yet do is predict, before the first sip of formula, which child will respond. Closing that gap, the review concludes, may be a small but crucial step toward individualized therapy for every child with Crohn’s disease, transforming a treatment that sometimes works brilliantly into one that works brilliantly for the right patients, chosen in advance.

Subject of Research: Predictors of response to nutritional therapy in pediatric Crohn's disease

Article Title: Current perspectives and future horizons in predicting response to nutrition therapy in children with Crohn’s disease – a narrative review

Article References: Krawiec, P., & de Ridder, L. (2026). Current perspectives and future horizons in predicting response to nutrition therapy in children with Crohn’s disease – a narrative review. Pediatric Research. https://doi.org/10.1038/s41390-026-05559-3

Image Credits: AI Generated

DOI: 10.1038/s41390-026-05559-3

Keywords: Crohn's disease, exclusive enteral nutrition, pediatric IBD, precision nutrition, faecal calprotectin, gut microbiome, Crohn's disease exclusion diet, personalized medicine, multiomics, biomarkers, mucosal healing, narrative review