Early life gut microbiota profiles linked to synbiotic formula effects: a randomized clinical trial in European infants.

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• Infant gut colonisation differs in vaginal versus cesarean section deliveries and between breastfed and infant formula practices.
• Both enriched strain-specific probiotic and standard infant formula were shown to have a marked effect on microbiota colonisation in infants at age 4 months.
• By the age of 2 years, however, there is no significant difference between breastfed and formula fed infants.

Introduction

This randomised controlled intervention study compared gut health parameters with the use of a synbiotic pre- and probiotic strain enriched infant formula with human milk and standard formula at three intervals over a period of 2 years.

Methods

This was a double-blinded controlled study of 540 infants from France and Belgium. Participants were randomly allocated to 2 formula groups (n = 230 Control Formula (CF), n = 230 Intervention Formula (IF)) and the breastfed reference group (n = 80) as well as delivery mode (Cesarean and vaginal delivery). The synbiotic IF was a standard infant formula enriched with prebiotic GOS (0.02 g/g) and the probiotic strain L. fermentum CECT5716 (at least 1.0 × 106 cfu/g).

Stool analysis was conducted at three time intervals, 4, 12, and 24 months (infant age). Biomarkers included short chain fatty acids, pH, secretory IgA, calprotectin, and various bacterial phyla via microbiota analysis.

Results

• At 4 months, the IF group tested higher for Bifidobacterium spp., and Lactobacillaceae and lower occurrence of Blautia spp., as well as Ruminoccocus gnavus and relatives compared to CF. They also had lower fecal pH and butyrate levels
• Both the formula cohorts had lower SigA and more basic pH values than the human milk cohort, as well as higher prevalence of anaerobes belonging to the bacterial genera Akkermansia, Collinsella, and Faecalibacterium.
• By age 24 months, the IF cohort exhibited increased levels of Akkermansia, Escherichia-Shigella, and R.gnavus. However there were no significant differences between the formula fed and human milk cohort at this time interval.
• The differences observed at 4 months disappeared over time, except for a significantly higher relative abundance of bifidobacteria and Faecalibacterium spp. in IF infants at 12 months compared with CF infants.

Conclusion: Although prominent differences between the cohorts were observed at 4 months, it appears that by the age of 2 years, there is little observable difference. This is most likely due to gut ecosystem maturation. The paper draws attention to the fact that changes to microbiota following treatment were more pronounced in infants who tested lower in occurrences of Bacteroides spp at age 4 months. Of note is the prevalence of cesarean birth deliveries in this cohort thereby indicating potential improved alternative feeding options when breastfeeding is not possible for these infants.

• Probiotic L.fermentum and prebiotic galacto-oligosaccharide enriched infant formula appears to the improve infant microbiome, when compared to that of breastfed infants.
• The most receptive infants were those born via cesarean section.

Limitations to consider:

• The sample groups were from France and Belgium, with no indication as to culture, socio-economic, or sex distribution.
• The two infant formula groups were n=230 each with only 80 infants in the breastfed reference group.
• There was no indication of maternal diet practices pre-, during, and post- pregnancy.
• Stool samples were not collected from the infants at baseline visit prior to formula intervention.

• Future studies need to include more diverse cultural and socio-economic cohorts to ascertain the potential influence of parental diet in baseline infant microbiome.
• It is imperative to establish what role solid food choices, generally introduced at 6 months, might have on gut ecosystem maturation.
• It would be useful to have a larger cesarean section birth cohort to compare to vaginal deliveries for more definitive results.