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. 2019 Jan 15:9:5.
doi: 10.1186/s13601-019-0241-3. eCollection 2019.

A specific synbiotic-containing amino acid-based formula in dietary management of cow's milk allergy: a randomized controlled trial

Adam T Fox  1 , Harm Wopereis  2   3 , Marleen T J Van Ampting  2 , Manon M Oude Nijhuis  2 , Assad M Butt  4 , Diego G Peroni  5 , Yvan Vandenplas  6 , David C A Candy  4 , Neil Shah  7 , Christina E West  8 , Johan Garssen  2   9 , Lucien F Harthoorn  2 , Jan Knol  2   3 , Louise J Michaelis  10 ; ASSIGN study group
Affiliations

A specific synbiotic-containing amino acid-based formula in dietary management of cow's milk allergy: a randomized controlled trial

Adam T Fox et al. Clin Transl Allergy. .

Abstract

Background: Here we report follow-up data from a double-blind, randomized, controlled multicenter trial, which investigated fecal microbiota changes with a new amino acid-based formula (AAF) including synbiotics in infants with non-immunoglobulin E (IgE)-mediated cow's milk allergy (CMA).

Methods: Subjects were randomized to receive test product (AAF including fructo-oligosaccharides and Bifidobacterium breve M-16V) or control product (AAF) for 8 weeks, after which infants could continue study product until 26 weeks. Fecal percentages of bifidobacteria and Eubacterium rectale/Clostridium coccoides group (ER/CC) were assessed at 0, 8, 12, and 26 weeks. Additional endpoints included stool markers of gut immune status, clinical symptoms, and safety assessments including adverse events and medication use.

Results: The trial included 35 test subjects, 36 controls, and 51 in the healthy reference group. Study product was continued by 86% and 92% of test and control subjects between week 8-12, and by 71% and 80%, respectively until week 26. At week 26 median percentages of bifidobacteria were significantly higher in test than control [47.0% vs. 11.8% (p < 0.001)], whereas percentages of ER/CC were significantly lower [(13.7% vs. 23.6% (p = 0.003)]. Safety parameters were similar between groups. Interestingly use of dermatological medication and reported ear infections were lower in test versus control, p = 0.019 and 0.011, respectively. Baseline clinical symptoms and stool markers were mild (but persistent) and low, respectively. Symptoms reduced towards lowest score in both groups.

Conclusion: Beneficial effects of this AAF including specific synbiotics on microbiota composition were observed over 26 weeks, and shown suitable for dietary management of infants with non-IgE-mediated CMA.Trial Registration NTR3979.

Keywords: Bifidobacterium breve M-16V; Cow’s milk allergy; Gut microbiota; Prebiotic; Probiotic; Symptoms.

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Figures

Fig. 1
Fig. 1
CONSORT diagram showing the flow of subjects in the randomized arms. ITT intention to treat. Early withdrawal-related adverse events were constipation (n = 1) and infantile colic (n = 1) and a related serious adverse event (n = 1) was viral laryngitis. The events were reported as unlikely and not related to study formula
Fig. 2
Fig. 2
Percentages of bifidobacteria (a) and ER/CC (b) at weeks 0 to 26 in ITT. The grey shaded area represents the sample 25th to 75th percentile of the healthy reference group (healthy, breastfed subjects—age matched to CMA subjects at week 8) and the grey horizontal lines represent the minimum and maximum values of this healthy reference group. The bottom and top edges of the box are located at the sample 25th and 75th percentiles. The center horizontal line is drawn at the 50th percentile (median). The whiskers of the box plots show the minimum and maximum values. P values are based on ANCOVA comparing test versus control with week 8, 12 or 26 values as outcome, stratification factor (skin or gastrointestinal symptoms) and imputed baseline values as covariate and intervention as fixed effect
See this image and copyright information in PMC

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