Bioactive Metabolites in Neonates of Mothers Supplemented with Bifidobacterium animalis are Linked to Microbiota-related Compounds in Milk and Maternal Plasma in Mice

Maternal supplementation with Bifidobacterium animalis subsp. lactis (B. lac) in mice improves influenza virus infection resolution. Transmission pathways from mother to neonate are not fully identified. Benefits may be linked to metabolic modulations in plasma of mothers and in milk metabolome. To examine how maternal supplementation with B. lac impact maternal and offspring metabolomic profiles, pregnant mice were orally supplemented with B. lac for the five last days of pregnancy and the three first days of lactation (n=8-10). Plasma from mothers and offsprings and gastric contents (digested milk) from the offspring's stomach, were collected and high-throughput non-targeted metabolomic assays were applied. Hierarchical All-against-All association (HAllA) based on Spearman's rank correlations was performed to correlate the significant metabolites modulated by the maternal B. lac supplementation between the different compartments. The level of short-chain fatty acids (SCFAs) isocaproate and caproate, enriched in digested milk, showed a strong positive correlation with the level of equol glucuronide, the most affected bioactive compound in neonatal plasma with maternal B. lac supplementation. Moreover, milk isocaproate abundance also correlated positively with another bioactive metabolite in plasma offspring, the cinnamoylglycine. Additionally, the reduction of secondary bile acids (SBAs) and increase of vitamin E in maternal plasma were negatively and positively associated with SCFAs in digested milk, respectively. We identified several correlated microbial metabolites in the mother-milk-neonate relationship under maternal probiotic supplementation providing some insights into interactions between interconnected biological systems during perinatal period. While correlation does not imply causation, these findings provide valuable leads for future hypothesis-driven studies.