A synbiotic-containing amino-acid-based formula improves gut microbiota in non-IgE-mediated allergic infants

Abstract

BackgroundPrebiotics and probiotics (synbiotics) can modify gut microbiota and have potential in allergy management when combined with amino-acid-based formula (AAF) for infants with cow's milk allergy (CMA).MethodsThis multicenter, double-blind, randomized controlled trial investigated the effects of an AAF-including synbiotic blend on percentages of bifidobacteria and Eubacterium rectale/Clostridium coccoides group (ER/CC) in feces from infants with suspected non-IgE-mediated CMA. Feces from age-matched healthy breastfed infants were used as reference (healthy breastfed reference (HBR)) for primary outcomes. The CMA subjects were randomized and received test or control formula for 8 weeks. Test formula was a hypoallergenic, nutritionally complete AAF including a prebiotic blend of fructo-oligosaccharides and the probiotic strain Bifidobacterium breve M-16V. Control formula was AAF without synbiotics.ResultsA total of 35 (test) and 36 (control) subjects were randomized; HBR included 51 infants. At week 8, the median percentage of bifidobacteria was higher in the test group than in the control group (35.4% vs. 9.7%, respectively; P<0.001), whereas ER/CC was lower (9.5% vs. 24.2%, respectively; P<0.001). HBR levels of bifidobacteria and ER/CC were 55% and 6.5%, respectively.ConclusionAAF including specific synbiotics, which results in levels of bifidobacteria and ER/CC approximating levels in the HBR group, improves the fecal microbiota of infants with suspected non-IgE-mediated CMA.

Figure 1

CONSORT diagram showing the flow of subjects in the randomized arms. ITT, intent to treat. Early withdrawal-related adverse events were constipation (n=1) and infantile colic (n=1), and related serious adverse event (n=1) was viral laryngitis. The events were reported as unlikely and not related to study formula.

Figure 2

Percentages of bifidobacteria (a) and adult-like ER/CC (b) at weeks 0 and 8 in subjects given test formula or control formula (ITT). The gray shaded area represents the sample 25th to 75th percentile of the healthy reference group (healthy, breastfed subjects), and the gray horizontal lines represent the minimum and maximum values of the healthy reference group. P values are based on ANCOVA comparing test vs. control groups with week 8 values as outcome, stratification factor (skin or gastrointestinal symptoms) and imputed baseline values as covariate and intervention as fixed effect, respectively.

Figure 3

Parent-reported, clinician-evaluated symptoms at weeks 0, 1, 4, and 8 assessed on a 4-point rating scale specific for each symptom. Skin symptoms (redness, oozing, crusting, itchiness, dryness, and nappy rash) were rated as 1: none, 2: slight, 3: some, and 4: a lot. Respiratory symptoms blocked nose and wheezing rated as 1: none, 2: mild, 3: moderate, and 4: severe, and coughing was rated as 1: none, 2: one to two times/day, 3: three to five times/day, and 4: more than five times/day. General and gastrointestinal symptoms: vomiting was rated as 1: none, 2: one to two times/day, 3: three to four days/day, and 4: more than four times/day; spitting-up as 1: none, 2: after some feeds, 3: after all feeds, and 4: between and after feeds; gas/wind as 1: none; 2: slight; 3: some; and 4: a lot; sleep pattern last night as 1: normal, 2: awake once, 3: awake two to three times, and 4: awake more than three times; ease of settling or burping after feeds as 1: no problem at all, 2: slight difficulty, 3: some difficulty, and 4: very difficult; visual signs of discomfort (e.g., back arching) as 1: none, 2: slight, 3: some, and 4: a lot; and crying (because of irritability) as 1: none, 2: up to 1 h, 3: 1–3 h, and 4: more than 3 h. Data are shown as mean values±95% confidence interval limits.