Human milk miRNAs associate to maternal dietary nutrients, milk microbiota, infant gut microbiota and growth.

Clinical nutrition (Edinburgh, Scotland). 2023;42(12):2528-2539
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Human milk is a source of nutrition during the early stages of development. Human milk contains nutritive and non-nutritive bioactives such as microRNAs (miRNAs or miRs). These bioactives likely program an infant's growth, development, and physiological systems (i.e., immune system, brain, liver). The aim of this study was to examine the potential impact of maternal diet on human milk miRNAs profile and the link to microbiota. This study was an observational study which included a subset of 60 healthy lactating women (n = 30 milk samples in each cluster). Results showed that that: - human milk miRNA's profile was altered based on maternal dietary protein source (plant or animal protein). - miRNA features were distinct based on maternal diet intake and correlated with dietary plant polyphenols, and milk microbiota. - milk miRNAs, irrespective of maternal dietary source, have a strong correlation with infant gut microbiota early in life as well as to infant anthropometric measures. Authors concluded that their findings extend current knowledge that milk miRNAs are differentially expressed based on maternal protein source, associate with specific set of milk microbiota and maternal intake of polyphenols, and infant microbiota for optimal growth and development.

Abstract

BACKGROUND Maternal diet influences the milk composition, yet little information is available on the impact of maternal diet on milk miRNAs expression. Further, the association of human milk miRNAs to maternal diet and milk microbiota is not explored. In addition, the role of milk miRNAs on the infant gut microbiota, infant growth and development has not been investigated. METHODS Milk samples were collected from 60 healthy lactating women at ≤15d post-partum, HTG transcriptome assay was performed to examine milk miRNA profile. Maternal clinical and dietary clusters information were available and infant anthropometric measures were followed up to one year of age. Milk and infant microbiota were analyzed by 16S rRNA gene sequencing and integrative multi-omics data analysis was performed to identify potential association between microRNA, maternal dietary nutrients and microbiota. RESULTS Discriminant analysis revealed that the milk miRNAs were clustered into groups according to the maternal protein source. Interestingly, 31 miRNAs were differentially expressed (P adj < 0.05) between maternal dietary clusters (Cluster 1: enriched in plant protein and fibers and Cluster 2: enriched in animal protein), with 30 miRNAs downregulated in the plant protein group relative to animal protein group. Pathway analysis revealed that the top enriched pathways (P adj < 0.01) were involved in cell growth and proliferation processes. Furthermore, significant features contributing to the clustering were associated with maternal dietary nutrients and milk microbiota (r > 0.70). Further, miR-378 and 320 family miRNAs involved in adipogenesis were positively correlated to the infant BMI-z-scores, weight, and weight for length-z-scores at 6 months of age. CONCLUSIONS Maternal dietary source impacts the milk miRNA expression profile. Further, miRNAs were associated with maternal dietary nutrients, milk microbiota and to the infant gut microbiota and infant growth and development. CLINICAL TRIAL The study is registered in ClinicalTrials.gov. The identification number is NCT03552939.

Lifestyle medicine

Fundamental Clinical Imbalances : Digestive, absorptive and microbiological
Patient Centred Factors : Mediators/Human milk
Environmental Inputs : Diet ; Nutrients ; Microorganisms
Personal Lifestyle Factors : Nutrition
Functional Laboratory Testing : Not applicable
Bioactive Substances : Polyphenols

Methodological quality

Jadad score : Not applicable
Allocation concealment : Not applicable
Publication Type : Clinical Trial ; Journal Article

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