Koen Huysentruyt

Background/Objectives: Lactose intolerance (LI), irritable bowel syndrome in adults (IBS) and recurrent abdominal pain (RAP) in children are frequently diagnosed worldwide. This systematic review aimed to assess the effects of dietary reduction in lactose on symptoms, quality of life and healthcare visits in IBS and children with recurrent abdominal pain. Methods: PubMed, Cochrane Library, Embase and Lilacs were searched for studies on IBS and RAP investigating the effect of a reduction of dietary intake of lactose for at least 4 weeks on abdominal pain, stool characteristics, bloating and distension, and quality of life published up to 15 August 2026. No restriction in language, publication type or data limit was applied. Four reviewers independently screened the abstracts for eligibility, and risk of bias was assessed by two reviewers with ROBINS-2. Disagreements were resolved by consensus or consulting with a senior investigator. Results were summarised in tabular form. The systematic review was registered on PROSPERO (CRD42024617161). Results: Eighteen studies met eligibility criteria based on the title and Upon review of full-text articles, three studies in adults and six studies in children were retained for data extraction. Lactose breath tests (LBTs) were performed in all studies. All but one study prospectively compared patient cohorts. IBS was defined by Manning criteria in two studies and Rome II criteria in one study. Only patients with a positive LBT were subjected to dietary intervention in eight of nine studies. No control group was included in one of three and three of six of the studies in adults and children, respectively. None of the studies compared symptomatic evolution based on validated questionnaires. Improvement in pain was reported by two of three and five of six of the studies on IBS and RAP, respectively. The risk of bias was high for all studies. No study assessed quality of life. Conclusions: Current evidence in support of dietary lactose reduction in patients with IBS and RAP is limited due to a high risk of bias, the use of old criteria, the absence of a valid comparator group and poorly defined outcomes. A positive LBT was associated with improvement in pain after a lactose-free diet. Future studies on the role of lactose restriction in IBS and RAP should recruit patients based on current diagnostic criteria and assess outcome by validated measures, preferentially applying a randomised controlled design.

Objectives: Identifying predictors of clinical remission in pediatric ulcerative colitis (UC) will impact the therapeutic approach. We aimed to predict time to first (TFR), corticosteroid‐free (TCSFR, ≥3 months corticosteroid withdrawal), and sustained remission (TSR, ≥6 months). Methods: This retrospective study analyzed de‐identified prospectively collected data from 2383 patients enrolled in ImproveCareNow (2007–2023). We included UC patients under 18 years at diagnosis. Remission was defined as a Pediatric UC Activity Index (PUCAI; 0.05) at T0 and history of severe UC (hazard ratio [HR] = 1.142, p = 0.05) before inclusion. In patients not reaching remission at T1 (subgroup; n = 964), TFR was predicted by PUCAI (confounder; moderate HR = 0.867 or severe disease HR = 0.697, p < 0.1) at T1 and history of severe UC (HR = 1.292, p = 0.007) before T1 (mean 25 days SEM 0.7). Mean TCSFR was 569.6 days, predicted by PUCAI (only mild HR = 0.728 and moderate HR = 0.559, p < 0.001) and use of corticosteroids (HR = 0.668, p < 0.001) at T1 (mean 32 days SEM 0.9). Mean TSR was 631.0 days, predicted by PUCAI (only mild HR = 0.721 and moderate HR = 0.541, p < 0.001) and the use of oral aminosalicylates (HR = 0.793, p = 0.003) at T1 (mean 30 days SEM 0.7). Conclusions: Several clinical parameters in early disease course predict remission with increasing PUCAI as useful negative predictor.

1. Enteral nutrition (EN) is the preferred route of nutritional support for children who are unable to meet their nutritional requirements orally with a functioning gastrointestinal (GI) tract [1]....

Objectives: Identifying predictors of poor outcomes (POPO) in paediatric Crohn's disease (CD) may guide therapy. We assessed predictors of 2‐year non‐remission (primary outcome) and time to first remission (TFR), corticosteroid‐free remission (TCSFR, ≥3 months corticosteroid (CS) withdrawal and sustained remission (TSR, ≥6 months) (secondary outcomes) in paediatric CD. Methods: We retrospectively analysed prospectively collected data from 6959 paediatric CD patients (α = 0.05), using R 4.5.0 with multiple imputation, identified predictors for both outcomes (at 0, 1, 5, 6, 12, and 24 months). Results: For the primary outcome, 53/794 patients (6.7%) failed to achieve remission during 2‐year follow‐up. Female sex (odds ratio [OR] = 3.12, 95% confidence interval [CI] 1.48–6.55) and need for ustekinumab after 1 year (OR = 14.70, 95% CI 4.37–49.46) predicted non‐remission. For the secondary outcomes ( n = 3290), mean TFR, TCSFR and TSR were 4.5, 16.4, and 8.2 months, respectively. Longer TFR was predicted by female sex (hazard ratio [HR] = 0.81, 95% CI 0.71–0.92) and the need for infliximab (IFX, HR = 1.15, 95% CI 1.00–1.32) at first visit. Longer TCSFR was associated with female sex (HR = 0.85, 95% CI 0.78–0.93), race (white HR = 0.83, 95% CI 0.74–0.93 and Asian HR = 1.42, 95% CI 1.05–1.92) and type of treatment at first visit (faster if IFX, slower if CS or immunomodulators). For TSR, predictors included age at diagnosis (HR = 1.06, 95% CI 1.02–1.11) and body mass index (BMI) (HR = 0.97, 95% CI 0.94–1.00). Conclusions: Clinical parameters (female sex, younger age, and higher BMI) and therapeutic strategy (early/late use of biologicals) are POPO and associated with longer time to remission in paediatric CD.

Background/Objectives: Although cow’s milk allergy is the most common food allergy in infants, its diagnosis remains challenging. Conventional allergy tests, including skin-prick testing and serum-specific IgE, can support the diagnosis in cases with a clear clinical history; however, neither positive nor negative results are sufficient for a definitive diagnosis without confirmation via an oral food challenge or reintroduction. The basophil activation test has emerged as a promising adjunctive tool in the diagnosis of cow’s milk allergy. Methods: We searched in the electronic databases PubMed/MEDLINE and Google Scholar for English articles published up to March 2026, using combinations of the following keywords: “cow’s milk allergy,” “basophil activation test, “BAT”, “food allergy,” “oral food challenge,” “IgE-mediated,” “children,” and “pediatric.” Results: While its widespread use is currently limited by the lack of standardized protocols, the need for fresh blood samples, and restricted availability outside specialized centers, the basophil activation test has the potential to improve diagnostic accuracy and support clinical decision-making in IgE-mediated cow’s milk allergy. Importantly, basophil activation test may also reduce the number of oral food challenges by providing a safe, functional assessment of allergen reactivity, thereby minimizing patient risk and the burden of invasive testing. Conclusions: Further studies and validation are needed before the basophil activation test can be implemented as a routine diagnostic tool.

Background/Objectives: Although cow’s milk allergy is the most common food allergy in infants, its diagnosis remains challenging. Conventional allergy tests, including skin prick testing and serum-specific IgE, can support the diagnosis in cases with a clear clinical history; however, neither positive nor negative results are sufficient for a definitive diagnosis without confirmation via an oral food challenge or reintroduction. The basophil activation test has emerged as a promising adjunctive tool in this context. Methods. We searched in the electronic databases PubMed and Google Scholar combinations of the following keywords: “basophil activation test”, “BAT”, “cow’s milk allergy”, “CMA”. Results. While its widespread use is currently limited by the lack of standardized protocols, the need for fresh blood samples, and restricted availability outside specialized centers, the basophil activation test has the potential to improve diagnostic accuracy and support clinical decision-making in IgE-mediated cow’s milk allergy. Importantly, basophil activation test may also reduce the need for oral food challenge by providing a safe, functional assessment of allergen reactivity, thereby minimizing patient risk and the burden of invasive testing. Conclusion. Further studies and validation are needed before the basophil activation test can be implemented as a routine diagnostic tool.

Review Article Gelatin tannate in pediatric infectious gastroenteritis Yvan Vandenplas, Koen Huysentruyt

Background/Objectives: Worldwide, an estimated 20–30% of infants suffer from infant colic (IC), with excessive crying and unsettled behavior, during the first three months of life. These infants are often referred for a medical evaluation, but the pathogenesis of IC remains poorly understood. The aim of this narrative review is to critically appraise the available literature regarding the relation between IC and cow’s milk allergy (CMA). Methods: A literature search using the search strings cow’s milk allergy [MeSH Terms] OR food allergy [MesH Terms] AND colic [MeSH Terms] OR crying [MeSH Terms], limited to the English language, from inception to 15 June 2025, resulted in the identification of 135 articles. Of these, 18 clinical trials assessed the effect of a cow’s milk elimination diet on IC. Results: The role of CMA in IC in the absence of other allergic manifestations remains uncertain. However, when standard treatment of infant colic has failed and when other allergic symptoms are present, CMA may be considered. A diagnostic elimination diet which includes a 2–4-week trial of maternal cow’s milk elimination in breastfed infants or an extensively hydrolyzed cow’s milk or hydrolyzed rice formula should be performed. If the elimination diet results in a significant decrease in symptoms, reintroduction of cow’s milk protein into the diet is mandatory to fulfill the diagnostic criteria of CMA. Conclusions: Considering the limited current evidence, future research should prioritize large well-designed clinical trials with a focus on investigating CMA in colicky breastfed and formula-fed infants.

Importance: Different degrees of growth delay have been reported in children with Alagille syndrome (ALGS), yet these patients are routinely evaluated using standard growth charts. Objective: To develop condition-specific growth charts for ALGS using modern statistical approaches. Design, Setting, and Participants: This case series used data from the international, multicenter Global Alagille Alliance (GALA) study accrued between May 14, 2018, and March 20, 2023. Children born at full term between January 1, 1997, and August 31, 2019, with a clinically and/or genetically confirmed ALGS diagnosis and their native liver were included. Data from children with a known history of prematurity were excluded for the development of the growth charts. Data were analyzed from March 25, 2023, to December 30, 2024. Exposure: Growth of children with Alagille syndrome. Main Outcomes and Measures: Generalized additive models for location scale and shape were fitted to generate percentile plots for weight and height relative to age and superimposed on US Centers for Disease Control and Prevention (CDC) growth charts to illustrate differences in growth patterns compared with children with typical development. Results: Data from 1204 children with ALGS in overlapping cohorts (median [IQR] gestational age, 38 [37-39] weeks) were analyzed (1204 in the weight cohort; 695 boys [57.7%]; 9855 weight observations; 995 with neonatal cholestasis [82.6%]; 306 receiving a liver transplant [25.4%]; 98 deaths [8.1%] and 1106 in the height cohort, 635 boys [57.4%]; 8464 height observations; 906 with neonatal cholestasis [81.9%]; 287 receiving a liver transplant [25.9%]; 86 deaths [7.8%]) were included for the modeling of the weight-for-age and height-for-age charts, respectively. The median birth weight was 2.8 kg (IQR, 2.5-3.0 kg) for boys and 2.6 kg (IQR, 2.4-2.9 kg) for girls. The median birth length was 48.0 cm (IQR, 46.0-50.0 cm) for boys and 47.0 cm (IQR, 45.0-49.0 cm) for girls. The weight-for-age and height-for-age growth charts for boys and girls with AGLS differed significantly from CDC growth charts. The estimated height at age 18 years corresponded to the 50th percentile was 171.5 cm for boys and 156.5 cm for girls on the condition-specific charts vs 176 cm and 163 cm, respectively, on the CDC growth charts. Conclusions and Relevance: These findings suggest that condition-specific growth charts for ALGS may provide a crucial tool for clinicians to evaluate growth and aid in decision-making around listing children for liver transplant.

Background: The liver plays a critical role in metabolism and immune function, yet the contributions of its heterogeneous cell types to these processes remain unclear. While most liver studies focus on adults, pediatric liver diseases often present differently, underscoring the need for age-specific research. Methods: To better understand cellular drivers of childhood liver diseases, we generated single-cell RNA-sequencing maps of the normal pediatric liver and used this map to examine disease-related populations in biopsies from pediatric patients with intestinal failure–associated liver disease (IFALD). Results: The normal pediatric liver map consists of 42,660 cells from 9 donors under 17 years of age. Compared with normal adult liver (26,372 cells; 7 donors, age 26–69), pediatric livers exhibited differences in myeloid populations. Specifically, pediatric Kupffer-like cells ( MARCO + C1QA + VSIG4 +) exhibited higher expression of immune activation genes, including CCL4 , CCL3 , and IL1B . In vitro stimulation confirmed more IL-1β-secreting myeloid cells in pediatric versus adult livers, supporting these findings. Using the pediatric atlas as a reference, we analyzed 3 IFALD biopsies (11,969 cells; 3 donors, under 9 y of age) and identified increased expression of fibrosis-associated genes (eg, LY96 ) in Kupffer-like cells. In addition, mesenchymal cells in IFALD showed fibrotic gene modules resembling adult liver cells more than healthy pediatric cells. These signatures, undetectable when comparing IFALD to adult liver alone, highlight the value of a pediatric map. Conclusion: Taken together, our healthy pediatric liver atlas reveals distinct age-related signatures and provides a background against which to interpret pediatric liver disease data.