The purpose of this study was to evaluate the effects of 2 probiotic supplements on fecal microbiota, metabolites, and gut inflammation in preterm infants who are fed human milk. Using 16S rRNA gene sequencing and 1H nuclear magnetic resonance spectroscopy, researchers compared the effects of supplementing with Bifidobacterium longum subsp. infantis or Lactobacillus reuteri on the gut microbiota and fecal metabolome of infants. The intestinal inflammation was evaluated by measuring calprotectin in the feces. Human milk oligosaccharide (HMO) content was also determined by analyzing aliquots of human or donor milk given to each newborn. It turned out that the probiotic treatments all led to higher concentrations of the designated bacterial taxon. Despite consuming the same amount of HMOs from milk, infants fed L. reuteri had considerably greater fecal HMO levels. B. infantis supplemented infants had considerably higher levels of fecal metabolites linked to bifidobacteria fermentation products. Infants given B. infantis had lower fecal calprotectin than those given L. reuteri (P<0.01, Wilcoxon rank-sum test) and this trend was inversely correlated with the levels of the microbial metabolite indole-3-lactate (ILA). An HMO-catabolizing Bifidobacterium probiotic was shown to improve microbial metabolism of milk oligosaccharides and decrease intestinal inflammation in human milk-fed preterm neonates, as compared to a noncatabolizing Lactobacillus probiotic. The microbiota-metabolite-immune axis is potentially more activated in breastfed infants, making Bifidobacterium more beneficial for them.