Amino Acid Formula Containing Synbiotics in Infants with Cow's Milk Protein Allergy: A Systematic Review and Meta-Analysis

Nutrients. 2021 Mar 14;13(3):935. doi: 10.3390/nu13030935.


Cow's milk protein allergy (CMPA) is associated with dysbiosis of the infant gut microbiome, with allergic and immune development implications. Studies show benefits of combining synbiotics with hypoallergenic formulae, although evidence has never been systematically examined. This review identified seven publications of four randomised controlled trials comparing an amino acid formula (AAF) with an AAF containing synbiotics (AAF-Syn) in infants with CMPA (mean age 8.6 months; 68% male, mean intervention 27.3 weeks, n = 410). AAF and AAF-Syn were equally effective in managing allergic symptoms and promoting normal growth. Compared to AAF, significantly fewer infants fed AAF-Syn had infections (OR 0.35 (95% CI 0.19-0.67), p = 0.001). Overall medication use, including antibacterials and antifectives, was lower among infants fed AAF-Syn. Significantly fewer infants had hospital admissions with AAF-Syn compared to AAF (8.8% vs. 20.2%, p = 0.036; 56% reduction), leading to potential cost savings per infant of £164.05-£338.77. AAF-Syn was associated with increased bifidobacteria (difference in means 31.75, 95% CI 26.04-37.45, p < 0.0001); reduced Eubacterium rectale and Clostridium coccoides (difference in means -19.06, 95% CI -23.15 to -14.97, p < 0.0001); and reduced microbial diversity (p < 0.05), similar to that described in healthy breastfed infants, and may be associated with the improved clinical outcomes described. This review provides evidence that suggests combining synbiotics with AAF produces clinical benefits with potential economic implications.

Keywords: allergy; amino acid formula; clinical outcomes; cow’s milk protein allergy; gut microbiome; paediatrics; synbiotics.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Amino Acids / administration & dosage*
  • Humans
  • Infant
  • Infant Formula / chemistry*
  • Milk Hypersensitivity / prevention & control*
  • Synbiotics / administration & dosage*


  • Amino Acids