Prior research has suggested that specific single nucleotide polymorphisms associated with allergies may carry a risk for functional gastrointestinal disorders (FGIDs). Cow’s milk allergy (CMA) is common in children, and treatment often consists of using hydrolyzed casein formula to reduce inflammation. Probiotics also can be used to treat CMA as the disorder is associated with intestinal dysbiosis. Thus, the authors proposed that use of hydrolyzed casein formula with supplementation with Lactobacillus rhamnosus GG (LGG) in children may reduce the risk of FGIDs in children by affecting both intestinal inflammation and dysbiosis. This study was prospective, non-randomized, and open and included children 4 to 6 years of age with a history of CMA in the past. CMA was defined strictly as occurring when a patient had a reaction using a double-blind, placebo-controlled, food challenge. If a patient was diagnosed with CMA, then they were treated with one standard hydrolyzed formula (Nutramigen, Mead John Nutrition) or the same standard hydrolyzed formula with the addition of Lactobacillus rhamnosus GG (Nutramigen LGG, Mead Johnson Nutrition). Multiple patient conditions were excluded from the study, including patients with other food allergies, other allergic conditions, and patients treated with other prior prebiotics or probiotics. The patients with CMA were compared to sex and age-matched controls. Clinical data was obtained on all enrolled study patients with CMA (including sociodemographic factors, family history of allergic disease, exposures, etc.). Patients then underwent Rome III diagnostic criteria using the Questionnaire on Pediatric Gastrointestinal Symptoms (QPGS) based on Rome III Criteria (QPGS-RIII) to document presence of FGIDs later in life.
The study compared 110 patients with CMA given hydrolyzed formula, 110 patients with CMA given hydrolyzed formula with LGG, and 110 control patients. Baseline demographic data were similar between all groups except that age of immune tolerance to cow’s milk protein was significantly older in patients who had received hydrolyzed formula compared to patients who had received hydrolyzed formula with LGG. An analysis of the presence of FGIDs in the 3 study groups demonstrated an incidence rate of 0.21 (95% CI, 0.12 to 0.29) in the control group, 0.40 (95% CI, 0.31-0.50) in the group who had received hydrolyzed formula, and 0.16 (95% CI, 0.090.23) in the group who had received hydrolyzed formula with LGG. This analysis demonstrated that children who had received hydrolyzed formula with LGG had significantly less risk of developing a FGID long-term compared to children who had received hydrolyzed formula alone (P < 0.001). This significance did not change when corrected for age of CMA diagnosis, breastfeeding and weaning duration, or having a first degree relative with a history of an FGID. This study suggests that children with a prior history of CMA may have an increased risk of developing FGIDs later in life, and probiotics (specifically LGG in this study) may have a protective effect. However, the intestinal microbiome is complex as is determining all causes of FGIDs (including issues involved with visceral hypersensitivity and stress potentially aggravating FGIDs). Thus, although this study is an important step in evaluating potential risk factors for developing FGIDs in children, much more work is needed in identifying specific stool microbiome genetic signatures in children with a history of CMA and subsequent FGIDs as well as identifying specific biomarkers which could prevent FGIDs long term.