Multiassay nutritional metabolomics profiling of low vitamin A status versus adequacy is characterized by reduced plasma lipid mediators among lactating women in the Philippines: A pilot study

Authors: JOHNSON, CATHERINE - California Polytechnic State University; ROSARIO, RODRIGO - California Polytechnic State University; BRITO, ALEX - First Moscow State Medical University; AGRAWAL, KARAN - University Of California, Davis; FANTER, ROB - California Polytechnic State University; LIETZ, GEORG - Newcastle University; HASKELL, MAJORIE - University Of California, Davis; ENGLE-STONE, REINA - University Of California, Davis; Newman, John; LA FRANO, MICHAEL - California Polytechnic State University

Submitted to: Nutrition Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/20/2022
Publication Date: 5/28/2022
Citation: Johnson, C.M., Rosario, R., Brito, A., Agrawal, K., Fanter, R., Lietz, G., Haskell, M., Engle-Stone, R., Newman, J.W., La Frano, M.R. 2022. Multiassay nutritional metabolomics profiling of low vitamin A status versus adequacy is characterized by reduced plasma lipid mediators among lactating women in the Philippines: A pilot study. Nutrition Research. 104:118-127. https://doi.org/10.1016/j.nutres.2022.05.007.
DOI: https://doi.org/10.1016/j.nutres.2022.05.007

Interpretive Summary: Vitamin A is important for many biological processes including growth, vision, immunity and reproduction. However, low vitamin A status is common among lactating women in low-income countries. To expand our understanding of the impact of vitamin A on metabolism, we used modern analytical approaches to assess changes in a broad array of small molecules in the plasma of lactating women with low vs adequate vitamin A status. In this pilot study, plasma was collected from lactating women in Samar, Philippines, based on plasma retinol concentrations indicating low (n=5) or adequate (n=5) vitamin A status. The samples were analyzed using six mass spectrometry-based metabolomics assays (oxylipins, endocannabinoids, bile acids, primary metabolomics, aminomics, and lipidomics) . Of these, the oxylipin mediators of inflammation were the most profoundly effected, being uniformly reduced. These changes are consistent with the reduction in immune function associated with low vitamin A status. Future studies with stronger study designs and larger sample size are needed to confirm and validate these preliminary results.

Technical Abstract: Background: Low vitamin A (VA) status is common among lactating women in low-income countries. Lactation has substantial effects on mother’s metabolism and VA is known to be needed in multiple biological processes, including growth, vision, immunity, and reproduction. Objective: The objective of this pilot study was to utilize metabolomics profiling to conduct a broad, exploratory assessment of differences in plasma metabolites associated with low VA status versus VA adequacy in lactating women. Methods: Plasma samples from lactating women who participated in a survey in Samar, Philippines, were selected from a cross-sectional study based on plasma retinol concentrations indicating low (VA-; n=5) or adequate (VA+; n=5) VA status (plasma retinol <0.8 or >1.05 µmol/L). The plasma results collected from six metabolomics assays (oxylipins, endocannabinoids, bile acids, primary metabolomics, aminomics, and lipidomics) were compared by group using liquid chromatography mass spectrometry. Results: Twenty-eight metabolites were significantly altered in the VA- versus VA+ status groups, with 24 being lipid mediators (p<0.05). These lipid mediators included lower concentrations of the arachidonic acid- and eicosapentaenoic acid-derived oxylipins, as well as lysophospholipids and sphingolipids, in the VA- group (p<0.05). Chemical similarity enrichment analysis identified HETEs, HEPEs, and DiHETEs as significantly altered oxylipin clusters (p<0.0001, false discovery rate (FDR) p<0.0001), as well as sphingomyelins, saturated lysophosphatidylcholines, phosphatidylcholines, and phosphatidylethanolamines (p<0.001, FDR p<0.01). Conclusions: The multi-assay nutritional metabolomics profiling of low VA status compared with adequacy in lactating women was characterized by reduced lipid mediator concentrations. Future studies with stronger study designs and larger sample size are needed to confirm and validate these preliminary results.