Prospective observational study of the impact of early-life feeding on gut microbiome development in caesarean-delivered infants: associations with clinician-confirmed illness

Caesarean section (C-section) born infants acquire a compromised gut microbiome at birth. This prospective observational study investigated the impact of early-life feeding on gut microbiome of C-section born infants and its association with clinician-confirmed, parent-reported illnesses in real-world setting. 192 healthy infants were enrolled and grouped by delivery mode and feeding option: CS-Control (n = 66, C-section, mixed-fed formula without probiotics), CS-Test (n = 55, C-section, mixed-fed a formula containing the synbiotics combination of scGOS/lcFOS 9:1 and Bifidobacterium breve M-16 V), and VD-Reference (n = 71, vaginal delivery, mixed-fed formula without probiotics). Stool samples were collected at six specific time points during the first year of life, including Day 0–2, Week 1, Week 2, Week 4, Week 12, and Month 12. At Month 12, logistic regression models were used to analyse the reported illnesses. CS-Control infants showed delayed Bifidobacterium colonization and reduced microbial diversity compared to VD-Reference. In contrast, this delay was absent in CS-Test infants, whose microbiome profile resembled those of VD-Reference by the first week. At Month 12, CS-Control infants had significantly higher odds of illness episodes compared to CS-Test (adjusted p = 0.022). These findings confirm that synbiotics can restore early Bifidobacterium colonization in C-section born infants and may support a healthy development in the first year of life. Therefore, tailored nutritional strategies, such as specific synbiotics, may offer opportunities to reduce disease risks that are associated with a compromised microbiome in early life.