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Lactation and Breast Milk—the Appropriate System for Postnatal Programming and Disease Prevention

A special issue of Nutrients (ISSN 2072-6643). This special issue belongs to the section "Nutrition in Women".

Deadline for manuscript submissions: 5 August 2025 | Viewed by 4690

Special Issue Editors


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Guest Editor
Department of Dermatology, Environmental Medicine and Health Theory, University of Osnabrück, Am Finkenhügel 7a, D-49076 Osnabrück, Germany
Interests: milk exosomes; milk-derived non-coding RNAs; milk signaling; epigenetic regulation; dietary effects on acne; milk consumption and diseases of civilization

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Guest Editor
Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry (IFMPEGKC), RWTH University Hospital Aachen, D-52074 Aachen, Germany
Interests: liver disease; fibrosis; biomarker; cytokines; chemokines; translational medicine
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Special Issue Information

Dear Colleagues,

During the last few decades, the scientific understanding of breast milk has evolved from being seen as a food source to being a complex system of maternal signaling and programming for the developing infant. Breast milk not only provides macro- and micronutrients but also important biomolecules with signaling functions, such as special lipids, signaling proteins found in milk fat globules, hormones, antibodies, and specialized carbohydrates that are crucial for the development of the infant’s intestinal microbiome. Additionally, breast milk provides a myriad of extracellular vesicles, including exosomes, which transport various small non-coding RNAs. These include microRNAs, circular RNAs, and long non-coding RNAs. These RNAs play key roles in regulating gene expression and epigenetic processes that are essential for the postnatal development of tissues and organs in the growing infant. Emerging evidence suggests that breast milk-derived exosomal microRNAs can modify gene expression in the infant. The most abundant microRNA found in breast milk and milk exosomes is microRNA-148a-3p, which suppresses DNA methyltransferase 1 (DNMT1) and p53 (TP53). This microRNA may therefore play a role in controlling postnatal epigenetic DNA methylation-dependent gene regulation as well as p53-dependent transcription. Breast milk can be seen as a mammalian program, a type of software, provided by the maternal lactation genome, which has been optimized over millions of year of mammalian evolution. According to the World Health Organization, breast milk is considered the ideal food for infants. However, this definition does not fully acknowledge the programming impact of breast milk on postnatal gene regulation of the infant that plays a critical role for the prevention of diseases of civilization.

The purpose of this Special Issue is to provide up-to-date evidence demonstrating that breast milk serves dual functions as both a source of nutrition and as a postnatal epigenetic programming system. This programming system is crucial for the appropriate development of the gastrointestinal, immunological, metabolic, and neuroendocrine systems, and ultimately helps to prevent diseases such as obesity, diabetes mellitus, and cancer. Breast milk ensures that the infant receives species- and genome-specific feeding and programming, which cannot be replicated by artificial substitutes. After birth, the infant´s development is not yet complete. The infant´s transition from the intrauterine environment to the extrauterine life is continued by the tight control of the mammary glands. This allows for both breast-mediated feeding and programming. No other mammalian species allows for interference with this physiological program during the lactation period, except for civilized humans who have unfortunately lost their connection to their own genomic control for species-specific postnatal development. As a result, they struggle with increasing rates of non-communicable diseases associated with modern civilization.

We would be delighted to receive your manucript as an expert in the field supporting our major focus on breast milk-derived infant programming.

Prof. Dr. Bodo Melnik
Prof. Dr. Ralf Weiskirchen
Guest Editors

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Keywords

  • breast milk
  • milk exosomes
  • milk-derived RNAs
  • milk signaling
  • gene regulation
  • signal transduction
  • nutrigenomics
  • western diet

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Published Papers (2 papers)

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Research

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13 pages, 578 KiB  
Article
From Warm to Cold: Feeding Cold Milk to Preterm Infants with Uncoordinated Oral Feeding Patterns
by Louisa Ferrara-Gonzalez, Ranjith Kamity, Zeyar Htun, Vikramaditya Dumpa, Shahidul Islam and Nazeeh Hanna
Nutrients 2025, 17(9), 1457; https://doi.org/10.3390/nu17091457 - 26 Apr 2025
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Abstract
Background/Objectives: Premature infants frequently experience feeding difficulties due to the disrupted coordination of sucking, swallowing, and breathing, increasing the risk of airway compromise. In adults with dysphagia, cold liquids can enhance swallowing by stimulating sensory receptors in the pharyngeal mucosa. We previously [...] Read more.
Background/Objectives: Premature infants frequently experience feeding difficulties due to the disrupted coordination of sucking, swallowing, and breathing, increasing the risk of airway compromise. In adults with dysphagia, cold liquids can enhance swallowing by stimulating sensory receptors in the pharyngeal mucosa. We previously demonstrated that short-duration feeding with cold liquid significantly reduces dysphagia in preterm infants; however, the impact of an entire feeding with cold milk remains unexplored. This study aimed to evaluate the safety of cold milk feedings in preterm infants with uncoordinated feeding patterns and their impact on their feeding performance. Methods: Preterm infants with uncoordinated feeding patterns (n = 26) were randomized to be fed milk at either room temperature (RT) or cold temperature (CT) using an experimental, randomized crossover design. We monitored axillary and gastric content temperatures, mesenteric blood flow, and feeding performance. Results: There were no significant differences in mesenteric blood flow Doppler measurements or axillary body temperatures between the CT and RT feeding conditions. However, a reduction in gastric content temperatures of 3.6 °F and 2.7 °F was observed at one and thirty minutes following CT feeding, respectively. No evidence of cold stress, increased episodes of apnea or bradycardia, gastric residuals, or emesis was noted in infants during or after the CT feeding condition. Feeding performance outcomes did not differ significantly regarding milk transfer rate (p = 0.781) or proficiency (p = 0.425). However, the quality score on the Infant-Driven Feeding Scale (IDFS) showed a significant improvement following CT feeding (p = 0.001). Conclusions: Cold milk feeding can be a safe therapeutic option for preterm infants. This underscores the potential for further comprehensive investigations to evaluate cold milk feeding as an effective therapeutic strategy for managing feeding and swallowing difficulties in preterm infants. The study was registered at clinicaltrials.org under #NCT04421482. Full article

Review

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36 pages, 2725 KiB  
Review
Risk of Fat Mass- and Obesity-Associated Gene-Dependent Obesogenic Programming by Formula Feeding Compared to Breastfeeding
by Bodo C. Melnik, Ralf Weiskirchen, Wolfgang Stremmel, Swen Malte John and Gerd Schmitz
Nutrients 2024, 16(15), 2451; https://doi.org/10.3390/nu16152451 - 28 Jul 2024
Cited by 2 | Viewed by 4100
Abstract
It is the purpose of this review to compare differences in postnatal epigenetic programming at the level of DNA and RNA methylation and later obesity risk between infants receiving artificial formula feeding (FF) in contrast to natural breastfeeding (BF). FF bears the risk [...] Read more.
It is the purpose of this review to compare differences in postnatal epigenetic programming at the level of DNA and RNA methylation and later obesity risk between infants receiving artificial formula feeding (FF) in contrast to natural breastfeeding (BF). FF bears the risk of aberrant epigenetic programming at the level of DNA methylation and enhances the expression of the RNA demethylase fat mass- and obesity-associated gene (FTO), pointing to further deviations in the RNA methylome. Based on a literature search through Web of Science, Google Scholar, and PubMed databases concerning the dietary and epigenetic factors influencing FTO gene and FTO protein expression and FTO activity, FTO’s impact on postnatal adipogenic programming was investigated. Accumulated translational evidence underscores that total protein intake as well as tryptophan, kynurenine, branched-chain amino acids, milk exosomal miRNAs, NADP, and NADPH are crucial regulators modifying FTO gene expression and FTO activity. Increased FTO-mTORC1-S6K1 signaling may epigenetically suppress the WNT/β-catenin pathway, enhancing adipocyte precursor cell proliferation and adipogenesis. Formula-induced FTO-dependent alterations of the N6-methyladenosine (m6A) RNA methylome may represent novel unfavorable molecular events in the postnatal development of adipogenesis and obesity, necessitating further investigations. BF provides physiological epigenetic DNA and RNA regulation, a compelling reason to rely on BF. Full article
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