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Purpose: The composition and the metabolic activity of the gut microbiota of breastfed and formula-fed infants has been the focus of several studies over the last two decades. Gene sequencing techniques and metabolomics in biological samples have led to expansion of our knowledge in this field. A more thorough comprehension of the metabolic role of the intestinal microbiota could assist and expedite the development of optimal feeding strategies. The aim of this systematic review is to present available data regarding the effect of the feed type on the infantile intestinal microbiota (microbial composition and metabolites) by DNA-sequencing and metabolome analysis of neonatal stool. Methods: A systematic search of the literature in PubMed was attempted to establish relevant studies. Randomized controlled trials studying the diversity and composition of gut microbiota and metabolites of infants that received different types of feed were included. The study subjects were infants/neonates born at term or preterm receiving either breast, donor, or formula milk. Formula could be either classic or fortified with probiotics, prebiotics, or both. The included trials compared the differences on metagenomics and metabolomics of infantile stool, aiming at investigating the beneficial effects of fortification of formula with synbiotics. Results: Out of 1452 papers identified by the initial search, seven were selected for inclusion, following screening for eligibility. Eligibility was determined by closer examination for relevance of the title, abstract, and subsequent full text. The results of these studies mostly support that the feed type modulates the microbiome composition. In terms of the alpha-diversity, no significant difference exists between the feeding groups, whereas significant differences were noted with regards to beta-diversity in breastfed and formula-fed infants. As for the microbial composition, the studies revealed different populations in the formula-fed group compared to the breastfed group at the phylum and genus level. Bifidobacteria supplementation of infant formula did not seem to change the proportions of Bifidobacterial sequences during the first year of life. Another finding according to the studies is that the pH of fecal samples in breastfed as well as prebiotic-supplemented formula-fed infants. was significantly lower than that of formula-fed infants. Infant milk formula with a mixture of prebiotics (GOS/FOS oligosaccharides) was shown to be capable of selectively stimulating the growth of Bifidobacteria with analogous changes in fecal pH and short-chain fatty acid content in fully formula-fed infants. Conclusions: Overall, there is evidence to support that feed type modulates the infants’ microbiome constitution. The impact of feeding on term and preterm microbiota could have potential benefits on intestinal functionality, immune system, and metabolism, and probably pursuing the host for life.

The Metagenomic and Metabolomic Profile of the Infantile Gut: Can They Be “Predicted” by the Feed Type?