The Impact of Maternal Supplementation of Fish Oil and/or Probiotics During Pregnancy on the Serum Metabolomic Profile From Infancy to Childhood: Secondary Analysis of a Randomized Placebo-Controlled Trial

Abstract

<p>Background<br>Supplementation with probiotics and fish oil may modify circulating serum metabolites, but the extent to which their impacts can be transferred from mother to child is unknown.<br>Objectives<br>To investigate the impact of perinatal exposure to fish oil and/or probiotics on serum metabolomic profile in early childhood.<br>Methods<br>Children (n = 300) of pregnant females receiving fish oil+placebo, probiotics+placebo, fish oil+probiotics, or placebo+placebo [fish oil: 1.9-g docosahexaenoic acid and 0.2-g eicosapentaenoic acid; probiotics: Lacticaseibacillus rhamnosus HN001 and Bifidobacterium animalis subsp. lactis 420] from early pregnancy to 6-mo postpartum were observed until 5–6 y of age. Serum metabolomic profiles were analyzed using nuclear magnetic resonance metabolomics. The intervention’s impact on the overall metabolomic profile was assessed using permutation analysis of variance with multi-omics factor analysis utilized to infer latent factors that capture main sources of variability within each group, followed by a univariate comparison between the intervention groups at each age. The time effect was analyzed using a mixed model.<br>Results<br>We observed significant differences in the concentrations of fatty acids and lipoproteins at 6 months across the intervention groups (false discovery rate < 0.05). The main effects included higher serum concentration of docosahexaenoic acid and n–3 fatty acids, a higher ratio of n–3/n–6 fatty acids in fish oil+placebo and fish oil+probiotics groups compared with placebo+placebo, along with higher concentrations of lipids and cholesterol derivatives in very large high-density lipoproteins. At 6 mo, there were no significant differences in these metabolites for the probiotics+placebo group compared to placebo+placebo. At 1, 2, and 5–6 y, a total of 24 metabolites were affected by the intervention (non-significant after multiple correction).<br>Conclusions<br>Maternal intervention with fish oil alone and in combination with probiotics induces alterations in the metabolic profile at 6 mo of age, as demonstrated by increased circulating n–3 fatty acids and lipids in high-density lipoproteins.<br></p>