Human Milk’s Messengers from Mother to Infant
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Analysis of microbial composition and sharing in low-biomass human milk samples: a comparison of DNA isolation and sequencing techniques
Human milk microbiome studies are currently hindered by low milk bacterial/human cell ratios and often rely on 16S rRNA gene sequencing, which limits downstream analyses. Here, we aimed to find a method to study milk bacteria and assess bacterial sharing between maternal and infant microbiota. We tested four DNA isolation methods, two bacterial enrichment methods and three sequencing methods on mock communities, milk samples and negative controls. Of the four DNA isolation kits, the DNeasy PowerSoil Pro (PS) and MagMAX Total Nucleic Acid Isolation (MX) kits provided consistent 16S rRNA gene sequencing results with low contamination. Neither enrichment method substantially decreased the human metagenomic sequencing read-depth. Long-read 16S-ITS-23S rRNA gene sequencing biased the mock community composition but provided consistent results for milk samples, with little contamination. In contrast to 16S rRNA gene sequencing, 16S-ITS-23S rRNA gene sequencing of milk, infant oral, infant faecal and maternal faecal DNA from 14 mother-infant pairs provided sufficient resolution to detect significantly more frequent sharing of bacteria between related pairs compared to unrelated pairs. In conclusion, PS or MX kit-DNA isolation followed by 16S rRNA gene sequencing reliably characterises human milk microbiota, and 16S-ITS-23S rRNA gene sequencing enables studies of bacterial transmission in low-biomass samples.
Milk-derived extracellular vesicles and gut health
Milk is a nutrient-rich liquid produced by mammals, offering various health benefits due to its composition of proteins, fats, carbohydrates, vitamins, and minerals. Beyond traditional nutritional aspects, recent research has focused on extracellular vesicles (EVs) found in milk and their potential health benefits, especially for gastrointestinal (GI) health. Milk-derived EVs have been shown to influence gut microbiota, promote gut barrier integrity, support tissue repair and regeneration, modulate immune responses, and potentially aid in managing conditions like inflammatory bowel disease (IBD) and colorectal cancer. This review discusses the current understanding of milk-EVs’ effects on gut health, highlighting their potential therapeutic applications and future research directions. These findings underscore the promising role of milk-derived EVs in advancing GI health and therapeutics, paving the way for innovative approaches in oral drug delivery and targeted treatments for GI disorders.
Clinical lactation studies. Acting on key recommendations over the last decade
Including lactating women in clinical trials is imperative to generate relevant drug exposure and safety data needed to advise on clinical use of drugs in this understudied population. Recent changes in perspectives, regulatory guidance, and international networks which outline pragmatic approaches for advancing the conduct of clinical lactation studies are discussed. Case studies demonstrating successful application of modeling and simulation to complement clinical lactation data for enhanced knowledge of infant drug exposure are presented.
A network analysis of postpartum depression and mother-to-infant bonding shows common and unique symptom-level connections across three postpartum periods
Postpartum depression and mother-to-infant bonding difficulties (MIBD), two issues crucial to maternal and infant mental health, often coexist and affect each other. Our study aims to dissect their complex relationship through a graphical LASSO network analysis of individual symptoms in 5594 Japanese postpartum women, whose geographical distribution was nationally representative. We identified ‘fear’, ‘enjoyment’, ‘overwhelm’, and ‘insomnia’ as common bridge symptoms linking postpartum depression and MIBD across three distinct postpartum periods. Moreover, ‘self-harm’ emerged as a bridge symptom in the first 6 months and the 7–12 month period, while ‘laugh’ was a bridge symptom in the first 6 months and the 13–24 month period. Notably, ‘self-blame’ was identified as a unique bridge symptom specific to the 13–24 month period. Our analysis highlights the complexities of symptom connectivity across postpartum stages and underscores the critical need for interventions that address both common and stage-specific bridge symptoms to effectively support maternal mental health and strengthen mother-to-infant bonding.
Neonatal microbiome in the multiomics era: development and its impact on long-term health
The neonatal microbiome has been the focus of considerable research over the past two decades and studies have added fascinating information in terms of early microbial patterns and how these relate to various disease processes. One difficulty with the interpretation of these relationships is that such data is associative and provides little in terms of proof of causality or the underpinning mechanisms. Integrating microbiome data with other omics such as the proteome, inflammatory mediators, and the metabolome is an emerging approach to address this gap. Here we discuss these omics, their integration, and how they can be applied to improve our understanding, treatment, and prevention of disease.
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