Introduction

β-casein, a major protein in cow’s milk, is divided into the A1 and A2 type variants. Digestion of A1 β-casein yields the peptide β-casomorphin-7 which could cause gastrointestinal (GI) discomfort but A2 milk containing only A2 β-casein might be beneficial than A1/A2 (regular) milk.

Aims & Methods

The aim of this study was to evaluate the differences in GI discomfort after ingestion of A2 milk and A1/A2 milk. A randomized, double-blind, cross-over human trial was performed in 40 subjects who experienced GI discomfort following milk consumption. For each intervention period, either A2 milk first (A2→A1/A2) or A1/A2 milk was first consumed for 2 weeks (A1/A2→A2) following a 2-week washout period. GI Symptom Rating Scale (GSRS) scores, questionnaire for digestive symptoms, and laboratory tests including fecal calprotectin were evaluated. For symptom analysis generalized estimating equations (GEE) gamma model was used.

Results

A2 milk increased bloating (P = 0.041) and loose stools (P = 0.026) compared to A1/A2 milk in GSRS. However, A2 milk caused less abdominal pain (P = 0.050), fecal urgency (P < 0.001) and borborygmus (P = 0.007) compared to A1/A2 milk in questionnaire for digestive symptoms. In addition, fecal calprotectin also decreased or less increased after consumption of A2 milk compared to A1/A2 milk (P = 0.030), and this change was more pronounced in males (P = 0.005) than in females. There were no significant adverse reactions during the trial.

Conclusion

A2 milk alleviated digestive discomfort in Koreans following A2 milk consumption (ClinicalTrials.gov NCT06252636 and CRIS KCT0009301).

Introduction

The identification of colonic stricture in patients with Crohn's disease (CD) often leads to surgery due to concerns about associated neoplasia. Nevertheless, information regarding the neoplastic risk associated to colonic stricture is still limited.

Aims & Methods

The objective of this study was to assess both the incidence of colonic stricture in pediatric-onset CD and the associated neoplastic risk at the population-based level. All patients diagnosed with CD before age 17 between 1988 and 2011, and included in a population-based registry, were followed until 2013. Colonic stricture was defined as a narrowing of the digestive lumen observed on endoscopic or radiological examination. Excluded were stricture in the ileocaecal valve, anal canal, or low rectum. Univariate risk factors for colonic stricture were explored using Cox proportional hazards models with time-dependent variables, and a multivariable Cox model analysis was performed.

Results

A total of 1,007 patients diagnosed with CD between 1988 and 2011 were included. Median age at diagnosis was 14.5 years [IQR: 12.0-16.1]. Throughout the follow-up period (median follow-up, 8.8 years [4.6-14.2]), patients were predominantly exposed to 5-aminosalicylates (88.1%), immunosuppressants (70.6%), and biologics (47.9%). Colonic stricture was diagnosed in 52 patients, including 11 at CD diagnosis. The cumulative incidence of colonic stricture in CD was 2.9% [1.8%-4.0%] at 5 years. The overall incidence rate of colonic stricture in CD was 5.4 cases/1000 person-years, 95% CI [4.1-7.1]. In multivariable analysis, an increased risk of colonic stricture was observed during periods of active disease (HR = 2.62, [1.40-4.89], p<0.01). Conversely, the absence of colonic involvement at diagnosis (HR = 0.18, [0.04, 0.80], p<0.05) or treatment with aminosalicylates (HR = 0.39, [0.19-0.79], p<0.05) was associated with a lower risk of colonic stricture. After a median follow-up of 6.4 [2.4-12.7] years, colonic stricture surgical resection was performed in 29 patients (55.8%). Colon adenocarcinoma was detected in one patient (1.9%) within 6 months after the diagnosis of colonic stricture.

Conclusion

In this population-based study of pediatric-onset Crohn's disease, 52 patients (5%) experienced colonic stricture, with a 2.9% incidence rate observed after 5 years of follow-up. Additionally, one patient (2%) presented with an associated adenocarcinoma.

Disclosure

M.F. has received lecture/consultant fees from AbbVie, Ferring, Tillotts, MSD, Biogen, Amgen, Fresenius, Hospira, Sandoz, Pfizer, Celgene, Gilead, Boehringer, Galapagos, Janssen, and Takeda. C.D. has received consultant fees from AbbVie. N.R. has received lecture/consultant fees from AbbVie and Takeda. The other authors state that they have no competing interests regarding this work to disclose.