A synbiotic mixture of scGOS/lcFOS and Bifidobacterium breve M-16V is able to restore the delayed colonization of bifidobacterium observed in C-section Delivered Infants

Objectives and study: Infants born by C-section miss the exposure to the maternal vaginal microbiota and this absence of microbial inoculation has been associated with a delayed colonization of commensal bacterial members such as Bifidobacterium. This compromised microbial inoculation may impact the health of the newborn and epidemiological data from cohort studies indicate associations between C-section and, immune and metabolic disorders such as asthma and obesity. The objective of this study was to determine the effect of a specific mixture of short-chain galactooligosaccharides and long-chain fructooligosaccharides (scGOS/lcFOS, ratio 9:1) and the probiotic strain Bifidobacterium breve M-16V in restoring the delayed colonization of Bifidobacterium observed in term C-section delivered infants. Methods: In a multi-country, double-blind, randomised controlled study, 153 infants born by elective C-section were randomised to receive (1) an infant formula supplemented with scGOS/lcFOS (0.8g/100ml) and B. breve M-16V (7.5×108CFU/ 100ml), or (2) a formula supplemented with scGOS/lcFOS (0.8g/100ml), or (3) a control formula from birth until age 4 months. As a reference group, 30 vaginally born, breast fed infants were studied in parallel. Stool samples were collected at day 3 and/ or day 5, week 2, week 4, week 8, week 12, week 16, and week 22 (6 weeks postintervention). The total Bifidobacterium gene count, several Bifidobacterium species and B. breve M- 16V were determined with molecular tools, pH and SCFA were also measured in the stool samples. Results: 129 randomized infants were included in the modified ITT data analysis with 45, 39 and 45 infants in the synbiotic, prebiotic and control group, respectively. The reference group consisted of 28 infants (mITT). All the study groups including the reference group were mixed-fed. The data confirmed the delayed colonization of Bifidobacterium in C-section delivered infants. The synbiotic supplementation resulted in a significant higher estimated mean of total bifidobacteria gene count from the first days of life (p{<}0.0001) and this bifidogenic effect remained significant until week 12 (p=0.032) compared to the control group. In the prebiotic group, the estimated mean of total Bifidobacterium gene count was comparable to the control group. In the synbiotic group, B. breve M-16V was still detected in 38.7 {%} of the infants at week 22 indicating a persistence of the probiotic strain. A significant lower estimated mean faecal pH was observed in the synbiotic group from the first days of life (p{<}0.0001) and this remained significant until 1 month of age (p=0.001) compared to the control group. A significant higher estimated mean amount of acetate was observed in the synbiotic group at day 3/5 (p{<}0.0001) compared to the control group. A lower number of subjects with adverse events of eczema/atopic dermatitis was reported in the synbiotic group (n=3) compared to the control (n=10), and prebiotic group (n=9), after correction for family allergy history (p{<}0.05). Conclusion: An infant formula supplemented with scGOS/lcFOS and B. breve M-16V is able to restore the delayed colonization of Bifidobacterium in C-section delivered infants from the first days of life. This phenomenon is associated with the creation of a favourable gut ecosystem milieu. These biological effects may have potential long term health benefit in C-section born infants.