Impact of infant nutrition on gut and brain nitrogenous metabolomes: Comparison of human milk and infant formula feeding in the minipiglet model.

The effect of infant nutrition on the metabolism of different body compartments is poorly described. Hence, the present study aimed to characterize the effect of human milk (HM) vs. infant formula (IF) feeding on metabolic mediators in key samples crucial for metabolic activity through the gut-brain axis during infant development, using the minipiglet as a human infant model. Eighteen 19-day-old piglets were fed HM or IF for six days. Thirty min after the last meal, colonic digesta, blood plasma, liver and six regions of the brain were sampled. Profiles of 45 metabolites (including proteinous amino acids, tryptophan (Trp) metabolites, polyamines, neurotransmitters) were determined using a targeted liquid chromatography and tandem mass spectrometry approach. Metabolic signatures of key organs involved in the gut-brain signal exchange were diet-dependent. The main dietary-induced differences in metabolite content occurred in the hippocampus (77% of the targeted metabolites quantified), plasma (47%), brainstem (17%), and colonic digesta (16%). These differences concerned Trp, Trp-derived metabolites, polyamines, some proteinous amino acids and neurotransmitters. Tryptophan was preferentially metabolized towards the kynurenine pathway in the colon and the hippocampus of HM-fed piglets. Differences in brain amino acid levels were associated with different brain polyamine and neurotransmitter contents in the hippocampus and, to a lower extent, in the other brain regions. Significant (P<0.05) correlations with specific bacterial genera and gene expressions were found. In the colon, Trp-derived metabolites such as kynurenine and tryptamine were positively and negatively correlated with Veillonella, respectively, and tryptamine levels may be related to the abundance of Ruminococcus genera. In the brain, the elevated level of the 5-hydroxyindolacetic acid (5-HIAA, from the serotonine pathway) in the HM brainstem may be related to the more abundant Bifidobacterium in HM-fed piglets. Finally, bacteria from the Firmicutes and Proteobacteria phyla may be involved in modulating polyamine production, as suggested by significant correlations between polyamine levels and bacterial genus abundances in the colon. Overall, the results confirmed the differential effect of HM vs. IF feeding on the microbiota-gut-brain axis and showed the high metabolic responsiveness of the hippocampus, probably related to specific nutritional needs and functionality in minipiglets.