Background: The aim of this study was to estimate the frequency of functional gastrointestinal disorders (FGIDs) in infants aged up to 12 months according to the new ROME IV criteria defining these disorders, and to describe the management of FGIDs in France. Methods: This French non-interventional, cross-sectional, and multicenter study was conducted among private-outpatient physicians who each included four consecutive patients aged up to 12 months. The frequency of FGIDs was described using the ROME IV criteria versus clinicians’ diagnosis. The characteristics of infants with and without FGID were compared, and the management of the FGIDs was described. Results: In the 1722 infants analyzed, the following frequencies were observed according to the ROME IV criteria versus the physicians’ diagnosis: regurgitation 41% versus 45%; colic 18% versus 30%; constipation 9% versus 19%; diarrhea 3% versus 8%. Of note, FGID infants were less frequently exclusively breastfeeding at the maternity hospital (p < 0.001), were introduced to cow’s milk earlier after leaving the maternity hospital (p < 0.001), and more frequently had symptoms suggestive of cow’s milk protein allergy (p < 0.001). Physicians frequently recommended an adapted infant formula (in 77% to 82% of cases depending on the FGID diagnosed) and prescribed a specific treatment in 51% to 66% of infants (probiotics: 35% to 64%). Conclusions: This real-world study confirms the high frequency of FGIDs in infants in France, and provides new information regarding the characteristics of FGID infants.

The neonatal development period from the time of birth can be considered the period of greatest physiological changes throughout the human lifespan. These changes are partly due to dietary or environmental factors and are also modulated by genetic, neuronal, and humoral influences. The focus of research is increasingly on the microbial colonization of the neonatal intestine, since the establishment of a healthy, symbiotic newborn microbiota not only corresponds closely with nutrient metabolism, immune functions, and growth, but also with the brain as part of the so-called “gut–brain axis”. At the same time, a critical time window of opportunity opens up for the early infant microbiota, which is accessible to modulating approaches in favor of normal infant development. Although the definition of “normal” microbiota in infants still remains challenging, the microbiota of infants delivered at term can be discussed as the gold standard—provided they were exclusively breastfed and have not been exposed to antibiotics. Advances in sequencing technologies now also allow us to identify and characterize the microbiota at the strain level and to provide the scientific rationale for new approaches to modulate the early-life microbiome in a more targeted and personalized way—applicable also for formula-fed children who cannot be supplied with human milk. This review addresses the challenges associated with the “healthy” development of a newborn during the first weeks and months of life and discusses potentially modifiable external factors in light of the requirements for the establishment of a functional gut microbiota, gastrointestinal system, and gut–brain axis.