Birth by cesarean section (C-section) is associated with a delayed colonization of bifidobacteria and Bacteroidota species with potential negative health consequences. Previously, an infant formula with a synbiotic mixture of short-chain galacto-oligosaccharides and long-chain fructo-oligosaccharides (scGOS/lcFOS [9:1]) and Bifidobacterium breve M-16V was found to restore the timely colonization of bifidobacteria in C-section born infants. In this study, we investigated the effect of this synbiotic mixture on gut microbiota development in C-section and vaginally-born infants participating in a growth equivalence trial (NCT03520764). Healthy, fully formula-fed Chinese infants were randomized to receive a partially hydrolyzed whey-based protein formula with the synbiotic mixture (n = 112), or an intact protein formula with scGOS/lcFOS (prebiotic, n = 112). Breastfed infants served as reference group (n = 60). Gut microbiota profiling by 16S rRNA gene sequencing of stools collected at baseline, 17 weeks (end of intervention) and 12 months of age was complemented with analysis of stool pH, short-chain fatty acids, lactic acids, and secretory IgA concentrations. Both the prebiotic and the synbiotic formula supported a dominant and diverse infant-type bifidobacterial community, but with increased abundance of Bifidobacterium breve in the synbiotic group. In C-section born infants (54.8% of randomized) the synbiotic but not the prebiotic, enhanced the bifidobacterial species diversity and showed restoration of Parabacteroides at 17 weeks, and Bacteroides spp. at 12 months closer to that of the vaginally-born infants. The synbiotic was confirmed to support the restoration of important gut colonizers in infants born by C-section with effects observed even beyond the intervention period.
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