Recommendations on the health outcomes of infant formula supplemented with biotics by the ESPGHAN Special Interest Group on Gut Microbiota and Modifications

For many years, biotics (including probiotics, prebiotics, human identical milk oligosaccharides, synbiotics, and postbiotics) have been added to infant formula to influence the gut microbiota of formula-fed infants, aiming to bring it closer to that of breastfed infants. The Special Interest Group on Gut Microbiota and Modifications (SIG-GMM) of the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) evaluated clinical outcomes from studies on biotic-supplemented infant formulas. A modified Delphi process was used to establish consensus on recommendations. This document is supported by separately published technical reviews, which synthesize the available evidence, analyze its limitations, and identify research gaps. ESPGHAN SIG-GMM concludes that infant formulas supplemented with one or more of the biotics evaluated so far fed to healthy infants do not raise safety concerns regarding growth, tolerance, and adverse effects. Based on available evidence, for some prebiotics (short-chain galacto-oligosaccharides/long-chain fructo-oligosaccharides), a weak recommendation in favor can be formulated because they soften stools by reducing stool consistency, and, to a lesser extent, increase stool frequency in presumed healthy infants. However, due to variability in study designs, intervention types, and measured outcomes, no clear conclusions can be drawn about their overall clinical benefits. Due to differences in interventions (e.g., duration, amount, and composition), inclusion criteria, and primary and secondary outcomes, for most biotics evaluated so far, no recommendations can actually be made “in favor” or “against.” This conclusion may reflect the limited data on specific biotics and outcomes because of the heterogeneity in the randomized controlled trials, rather than an actual lack of effect.