Compared with healthy breastfed infants, the gut microbiota of infants with CMA is often out of balance.6-10 This imbalance (dysbiosis) is typically characterised by:

Lower levels of beneficial Bifidobacteria7,8


Higher levels of adult-like bacteria such as Clostridia and Eubacteria6,7,9

A balanced gut microbiota is important for the development of the immune system.11-13

Breastmilk is the best source of nutrition for infants with CMA.14,15 It contains prebiotic oligosaccharides and beneficial bacteria that support the development of a balanced gut microbiota.16,17

Synbiotics are a combination of prebiotics and beneficial bacteria (probiotics) that work synergistically together.18

For formula-fed infants with CMA, over 10 years of research with allergic infants has shown the benefits of supplementing hypoallergenic formula with synbiotics.*6,10,19-26


Rebalances the gut microbiota6,10,21-24

Supports normal growth10,19-22

Improved clinical outcomes vs non- synbiotic formulas20,22,24-26

Randomised controlled trials

van der Aa 201024

12-week RCT of infants with AD (n=90)

Compared to an EHF without synbiotics, those in the synbiotic EHF group showed:

  • A gut microbiota closer to that of a healthy breastfed infant
  • Reduced constipation (p=0.01) and dry stools (p=0.001)
  • Reduced AD severity* (p=0.04)

van der Aa 201125

Follow-up from 12-week RCT of infants with AD (n=75)

Compared to an EHF without synbiotics, those in the synbiotic EHF group showed:

  •  A significantly lower prevalence of asthma-like symptoms at one-year follow-up (p=0.04)
  • Significantly less asthma medication use at one-year follow-up (p=0.02)

Systematic review

Sorensen 202122

Meta-analysis of four RCTs of infants with CMA (n=410)

Compared to an AAF without synbiotics, a synbiotic AAF supported:

  • A gut microbiota closer to that of a healthy breastfed infant
  • Fewer infants with infections (p=0.001)
  • Lower overall medication use (p<0.001)
  • Fewer hospital admissions due to infection (p=0.036)
  • Potential healthcare cost savings

Cohort studies

Sorensen 202126

Retrospective matched cohort study of infants with CMA using data from the THIN GP database (n=148)

Compared to an AAF without synbiotics, a synbiotic AAF was associated with:

  • Fewer GI, skin and/or respiratory symptoms* (p<0.001)
  • A lower rate of dietitian contacts (p=0.014)
  • Lower rates of infections (p<0.001) and medication prescriptions (p<0.001)
  • A shorter clinical journey(p<0.001)
  • Potential healthcare cost savings

Hubbard 202220

Single-arm, prospective study of infants with non-IgE CMA (n=29)

Compared to EHFs without synbiotics*, a synbiotic EHF supported:

  • Reduced incidence and severity of constipation, abdominal discomfort and wind (p<0.05)
  • Reduced rhinitis severity and itchy eyes (p<0.05)
  • Reduced AD severity(p=0.03)
  • A lower mean number of hospital visits and medication prescriptions in the 6 months after initiation(p<0.05)
  • Improved caregiver quality of life scores# (p=0.004)

Discover the only hypoallergenic formula range with synbiotics*†

Neocate Syneo

The only amino acid formula to contain synbiotics*

Aptamil Pepti Syneo

The only extensively hydrolysed formula to contain synbiotics*

*Synbiotic blend: Bifidobacterium breve M-16V (probiotic) & short and long-chain galacto- and/or fructo-oligosaccharides (prebiotic).

AAF: Amino Acid-based Formula; AD: atopic dermatitis; CMA: Cow’s Milk Allergy; EHF: Extensively Hydrolysed Formula; FAQL-PB: Food Allergy Quality of Life-Parental Burden; GI: gastrointestinal; HCP: healthcare professional; PO-SCORAD: Patient‐Orientated SCORing AD; RCT: Randomised Controlled Trial; THIN: The Health Improvement Network

van der Aa 201024: *Subgroup of n=48 infants with IgE associated AD.

Sorensen 202126: *Diarrhoea, constipation, flatulence, vomiting, reflux, bloody stools, mucus in stools, colic, eczema & urticaria. Clinical journey endpoint measured as being asymptomatic and not requiring a hypoallergenic formula prescription for at least 3 months.

Hubbard 202220: *Baseline non-synbiotic formula (n=27 out of n=29 well-established on a non-synbiotic EHF). Significant reduction in PO-SCORAD in subgroup of n=6 infants with more severe AD at baseline.

Follow-up arm of study n=13. #Assessed via FAQL-PB questionnaire.

1. Luyt, et al. Clin Experimental Allergy. 2014;44(5):642-72.

2. Meyer, et al. Pediatr Allergy Immunol. 2018;29(7):689-704.

3. Fox, et al. Clin Transl Allergy. 2019;9:40.

4. Koletzko, et al. JPGN. 2012;55(2):221-9.

5. Grimshaw, et al. Clin Transl Allergy. 2016;6:1.

6. Candy, et al. Pediatr Research. 2018;83(3):677-86.

7. Canani, et al. ISME J. 2016;10(3):742-50.

8. Harmsen, et al. JPGN. 2000;30(1):61-7.

9. Thompson- Chagoyan, et al. Pediatr Allergy Immunol. 2010;21:e394-400.

10. Burks, et al. Ped Allergy Immunol. 2015;26(4):316-22.

11. Martin, et al. Benef Microbes. 2010;1(4):367-82.

12. West, et al. J Allergy Clin Immunol. 2015;135(1):3-13.

13. Wopereis, et al. Pediatr Allergy Immunol. 2014;25(5):428-38.

14. WHO. Infant and  young child feeding, 2003.

15. Vandenplas, et al. J Asthma Allergy. 2021;14:1243-56.

16. Moossavi, et al. Front Pediatr. 2018;6:197.

17. Boehm, et al. J Nutr. 2007;137(3Suppl.2):847S-9S.

18. Pandey, et al. J Food Sci Technol. 2015;52(12):7577-87.

19. Harvey, et al. Pediatr Res. 2014;75(2):343-51.

20. Hubbard, et al. Immun Inflamm Dis. 2022;10(6):e636.

21. Abrahamse-Berkeveld, et al. J Nutr Sci. 2016;5:e42.

22. Sorensen, et al. Nutrients. 2021;13(3):935.

23. Fox, et al. Clin Transl Allergy. 2019;9:5.

24. van der Aa, et al. Clin Exp Allergy. 2010;40(5):795-804.

25. van der Aa, et al. Allergy. 2011;66(2):170-7.

26. Sorensen, et al. Nutrients. 2021;13(7):2205.

27. Kinnear, et al. 2021 HCP & parent survey – AAF + synbiotics, Poster presentation at the 8th International Conference on Nutrition & Growth conference, accepted May 2021. 
28. Data on file. 2023 Neocate Syneo and Pepti Syneo experience survey. Parent survey, n=90 parents, HCP survey n=120 HCPs. Jan 2023.
29. Market comparison of UK EHF and AAF data cards, September 2023.


Accurate at publication: October 2023


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