Discussion
milk allergic
LRTI, DISEASES
This RCT compared feeding prebiotic infant formula with the same prebiotic infant formula supplemented with probiotic One of the novelties of this study is the follow-up in the first year of life, i.e., until 6 months post-intervention. At 12 months of age, α-diversity was lower in the synbiotic group, which is consistent with a previous study that reported a slower increment in α-diversity in cow’s milk allergic infants fed another synbiotic formula compared with the same formula without synbiotics [The advantage of applying GC–MS/LC–MS as a functional readout of the synbiotic intervention was clearly shown as it detected increases in PLA, a by-product of phenylalanine metabolism in LAB [Gut microbial composition and functions develop as complementary foods are introduced [Deep metagenomic sequencing further revealed that The main strengths of our study are the randomized, controlled prospective design, repeated samplings, and the combined approach of 16S rRNA gene amplicon sequencing and metabolomics, thereby examining the synbiotic effects on both compositional and functional aspects of the gut microbiota. We also consolidated in silico the results obtained using 16S rRNA amplicon and shotgun sequencing by successful recovery of the MAGs of bacteria of interest. There are also limitations; we did not have fecal samples from all participants, and therefore, only a subset was available for gut microbiota analyses. Although commonly used for practical and ethical reasons, analysis of fecal samples may not be representative of changes occurring further up in the intestine. It would also have been valuable to analyze other metabolic aspects, e.g., the SCFA pattern; however, the GC–MS/LC-MC approach did not detect SCFAs, which are highly volatile compounds that require dedicated sample collection, metabolite extraction, and a targeted detection method. We also took the opportunity to characterize the metagenome and antimicrobial resistome in infants with antibiotic-treated LRTI and antibiotic-naïve controls, but these results are preliminary due to the small sample size. Finally, our results are restricted to healthy, term infants and may not be extrapolated to preterm infants nor infants with underlying diseases.