Impact of Early Life Nutrition on Immune System Development and Related Health Outcomes in Later Life

Editorial

25 March 2021

Editorial: Impact of Early Life Nutrition on Immune System Development and Related Health Outcomes in Later Life

Laxmi Yeruva

Daniel Munblit

and

Maria Carmen Collado

5,408 views

6 citations

Editors

Laxmi Yeruva

Arkansas Children's Nutrition Center, Agricultural Research Service (USDA)

Daniel Munblit

I.M. Sechenov First Moscow State Medical University

Maria Carmen Collado

Institute of Agrochemistry and Food Technology, Spanish National Research Council (CSIC)

Impact

Review

12 February 2021

Role of Human Milk Bioactives on Infants' Gut and Immune Health

Laura E. Carr

, 5 more and

Laxmi Yeruva

Exclusive human milk feeding of the newborn is recommended during the first 6 months of life to promote optimal health outcomes during early life and beyond. Human milk contains a variety of bioactive factors such as hormones, cytokines, leukocytes, immunoglobulins, lactoferrin, lysozyme, stem cells, human milk oligosaccharides (HMOs), microbiota, and microRNAs. Recent findings highlighted the potential importance of adding HMOs into infant formula for their roles in enhancing host defense mechanisms in neonates. Therefore, understanding the roles of human milk bioactive factors on immune function is critical to build the scientific evidence base around breastfeeding recommendations, and to enhance positive health outcomes in formula fed infants through modifications to formulas. However, there are still knowledge gaps concerning the roles of different milk components, the interactions between the different components, and the mechanisms behind health outcomes are poorly understood. This review aims to show the current knowledge about HMOs, milk microbiota, immunoglobulins, lactoferrin, and milk microRNAs (miRNAs) and how these could have similar mechanisms of regulating gut and microbiota function. It will also highlight the knowledge gaps for future research.

45,264 views

194 citations

Review

21 October 2020

The Impact of Milk and Its Components on Epigenetic Programming of Immune Function in Early Life and Beyond: Implications for Allergy and Asthma

Betty C. A. M. van Esch

, 5 more and

R. J. Joost van Neerven

Specific and adequate nutrition during pregnancy and early life is an important factor in avoiding non-communicable diseases such as obesity, type 2 diabetes, cardiovascular disease, cancers, and chronic allergic diseases. Although epidemiologic and experimental studies have shown that nutrition is important at all stages of life, it is especially important in prenatal and the first few years of life. During the last decade, there has been a growing interest in the potential role of epigenetic mechanisms in the increasing health problems associated with allergic disease. Epigenetics involves several mechanisms including DNA methylation, histone modifications, and microRNAs which can modify the expression of genes. In this study, we focus on the effects of maternal nutrition during pregnancy, the effects of the bioactive components in human and bovine milk, and the environmental factors that can affect early life (i.e., farming, milk processing, and bacterial exposure), and which contribute to the epigenetic mechanisms underlying the persistent programming of immune functions and allergic diseases. This knowledge will help to improve approaches to nutrition in early life and help prevent allergies in the future.

21,266 views

71 citations

Panels depict (A) cecum (B), proximal colon (C), distal colon, and (D) rectal contents at postnatal day (PND) 21. PLS-DA scores (i.e., individual piglet scores) for PLS-DA components (dimensions) 1 and 2 are displayed. Shadows with color are 95% confidence regions. Pink circles indicate individual HM-fed piglets and green circles indicate MF-fed piglets. Sample numbers were n = 8–11 per group.

Original Research

07 December 2020

Neonatal Diet Impacts the Large Intestine Luminal Metabolome at Weaning and Post-Weaning in Piglets Fed Formula or Human Milk

Fernanda Rosa

, 6 more and

Laxmi Yeruva

4,919 views

6 citations

Main metabolomics differences detected by comparing breast milk of overweight/obese mothers and lean ones in the different studies, and the potential short- and long-term effects in offspring.

Review

21 July 2020

The Human Breast Milk Metabolome in Overweight and Obese Mothers

Flaminia Bardanzellu

, 2 more and

Vassilios Fanos

14,095 views

39 citations

bIgG RSV binding and neutralization. Antibody binding of serial diluted palivizumab (Pali), IVIG or bIgG to RSV-A2 (closed symbols) or RSV-A2-RL-Line19F (open symbols) infected HEp-2 cells. RSV specific binding detected with αhIgG-RPE or αbIgG-Alexa647 and analyzed by flow cytometry. Data corrected for infection rate (A). HEp-2 cells were infected with RSV-A2 or RSV-A2-RL-Line19F which was pre-incubated for 1 h with a serial dilution of palivizumab, IVIG or bIgG. Infection was analyzed by flow cytometry, uninfected cells and no antibody incubation were set as 100 and 0% neutralization, respectively (B). Pre- and post-fusion F glycoprotein specific binding of palivizumab, IVIG and bIgG (C). Median with range of triplicate measurements are shown *P ≤ 0.05; **P ≤ 0.01.

Original Research

06 August 2020

Bovine IgG Prevents Experimental Infection With RSV and Facilitates Human T Cell Responses to RSV

Maaike Nederend

, 7 more and

Jeanette H. W. Leusen

4,101 views

18 citations

Original Research

11 September 2020

Administration of Extensive Hydrolysates From Caseins and Lactobacillus rhamnosus GG Probiotic Does Not Prevent Cow’s Milk Proteins Allergy in a Mouse Model

Karine Adel-Patient

, 5 more and

Christophe Junot

4,838 views

7 citations

Original Research

14 August 2020

Partial Degradation of Recombinant Antibody Functional Activity During Infant Gastrointestinal Digestion: Implications for Oral Antibody Supplementation

Baidya Nath P. Sah

, 9 more and

David C. Dallas

3,086 views

11 citations

Experimental protocol: BALB/cJ future dams were either kept naïve, moderately (intra-gastric gavage with BLG, and Cholera toxin) or highly (intra-peritoneal administration of BLG/alum) sensitized to BLG, or rendered tolerant to BLG (intra-gastric gavage with BLG alone) before mating with naïve males. At delivery, pups of treated mothers were replaced by pups from naïve-synchronized mothers in order to prevent interferences from in utero effects. Lactating mothers from each group then received BLG or PBS by i.g. gavage every other day, during the whole period of lactation. Breastmilk was collected 10 days post-partum by pooling stomach contents from 6 to 10 male pups per mother group to assess BLG, BLG specific antibodies, and BLG-immune complexes. The female progeny was then experimentally sensitized by i.p. injection of BLG and Alum when 5 weeks-old and BLG-specific IgE, IgG1, and IgG2a were measured 3 weeks later. A boost injection was performed 21 days after the first i.p. sensitization, and 2 weeks later, all mice were orally challenged with 15 mg of purified BLG. Plasma was collected 60 min later, both to assess allergic sensitization and elicitation of the allergic reaction. Mice were then sacrificed and spleens were pooled to assess ex vivo BLG-specific cytokine secretion.

Original Research

21 July 2020

Prevention of Allergy to a Major Cow's Milk Allergen by Breastfeeding in Mice Depends on Maternal Immune Status and Oral Exposure During Lactation

Karine Adel-Patient

, 4 more and

Valérie Verhasselt

3,842 views

17 citations

Human milk levels (μmol/L) from non-atopic (n = 62) and atopic (n = 47) mothers of (A) acetate, (B) butyrate and (C) formate. Lines indicate mean values.

Brief Research Report

21 July 2020

Human Milk From Atopic Mothers Has Lower Levels of Short Chain Fatty Acids

Lisa F. Stinson

, 11 more and

Anita L. Kozyrskyj

8,940 views

61 citations

Enriched pathways of MF compared to HM at PND21. (A) IPA of target predicted genes for downregulated miRNA in MF relative to HM at PND21. (B) IPA of target predicted genes for upregulated miRNA in MF relative to HM at PND21. The data represents from 9 MF and 9 HM fed piglets.

Original Research

23 June 2020

Neonatal Diet Impacts Circulatory miRNA Profile in a Porcine Model

Laura E. Carr

, 6 more and

Laxmi Yeruva

4,074 views

6 citations

Review

07 May 2020

Immunomodulation by Human Milk Oligosaccharides: The Potential Role in Prevention of Allergic Diseases

Marit Zuurveld

, 5 more and

Linette E. M. Willemsen

$Overview of the possible functions of HMOS related to the prevention of allergic diseases. The diversity in structures suggests engagement in several mechanisms related to maturation of the infant's gastrointestinal tract. (1) HMOS have shown to function as prebiotics and therefore stimulate growth of commensal bacteria. In addition, HMOS have shown to bind pathogens, thereby preventing binding of these pathogens to the intestinal epithelium itself and possible consequent infections. SCFAs produced during HMOS fermentation can enhance epithelial barrier integrity and locally and systemically modify immune responses. (2) HMOS can promote mucus production and epithelial tight junction integrity, thereby supporting the physical barrier between the intestinal epithelium and the gut content. (3) Several mechanisms by which HMOS directly affect the immune function have been described. Modulation of the response of DCs is one of those described mechanisms which may be relevant for the instruction of protective mucosal immune development. (4) Transportation of a small fraction of HMOS over the intestinal epithelium, results in systemic availability of these structures. This suggests an immunomodulatory role for HMOS, also beyond the gastrointestinal tract. All these HMOS related mechanisms can potentially enhance tolerance induction and therefore possibly prevent allergic diseases. Adjusted from Ayechu-Muruzabal et al. (48).$

The prevalence and incidence of allergic diseases is rising and these diseases have become the most common chronic diseases during childhood in Westernized countries. Early life forms a critical window predisposing for health or disease. Therefore, this can also be a window of opportunity for allergy prevention. Postnatally the gut needs to mature, and the microbiome is built which further drives the training of infant's immune system. Immunomodulatory components in breastmilk protect the infant in this crucial period by; providing nutrients that contain substrates for the microbiome, supporting intestinal barrier function, protecting against pathogenic infections, enhancing immune development and facilitating immune tolerance. The presence of a diverse human milk oligosaccharide (HMOS) mixture, containing several types of functional groups, points to engagement in several mechanisms related to immune and microbiome maturation in the infant's gastrointestinal tract. In recent years, several pathways impacted by HMOS have been elucidated, including their capacity to; fortify the microbiome composition, enhance production of short chain fatty acids, bind directly to pathogens and interact directly with the intestinal epithelium and immune cells. The exact mechanisms underlying the immune protective effects have not been fully elucidated yet. We hypothesize that HMOS may be involved in and can be utilized to provide protection from developing allergic diseases at a young age. In this review, we highlight several pathways involved in the immunomodulatory effects of HMOS and the potential role in prevention of allergic diseases. Recent studies have proposed possible mechanisms through which HMOS may contribute, either directly or indirectly, via microbiome modification, to induce oral tolerance. Future research should focus on the identification of specific pathways by which individual HMOS structures exert protective actions and thereby contribute to the capacity of the authentic HMOS mixture in early life allergy prevention.

15,355 views

90 citations

Overview of the potential effects of free glutamine and glutamate, selectively secreted in human milk by mammary gland cells, in the developing infant gut. The ↑ and ↓ indicate an upregulation and downregulation, respectively, of the corresponding target following in vitro and/or in vivo supplementation with glutamine (•) or glutamate (•). Effects are limited to those that are relevant in the context of allergic sensitization and infections. FAA, Free amino acid; IEC, Intestinal epithelial cell; IEL, Intraepithelial lymphocyte; GC, Goblet cell; TH1, T-helper 1 cell; TH2, T-helper 2 cell; IgA, Immunoglobulin A; F. prausnitzii, Faecalibacterium prausnitzii.

Review

28 May 2020

Free Amino Acids in Human Milk: A Potential Role for Glutamine and Glutamate in the Protection Against Neonatal Allergies and Infections

Joris H. J. van Sadelhoff

, 2 more and

Astrid Hogenkamp

13,899 views

47 citations

Factors shaping the human microbiome development. The neonatal microbiome is a delicate and highly dynamic ecosystem that undergoes rapid changes in composition in the first few years of life determined by several pre and perinatal factors. The maturation of the gut microbiota toward an adult-like structure largely occurs by the age of 2 or 3 years. Therefore, early infancy could be a critical period for modulating the microbiota to promote healthy growth and development.

Mini Review

23 April 2020

Microbiome Composition and Its Impact on the Development of Allergic Diseases

Diego G. Peroni

, 3 more and

Pasquale Comberiati

Allergic diseases, such as food allergy (FA), atopic dermatitis (AD), and asthma, are heterogeneous inflammatory immune-mediated disorders that currently constitute a public health issue in many developed countries worldwide. The significant increase in the prevalence of allergic diseases reported over the last few years has closely paralleled substantial environmental changes both on a macro and micro scale, which have led to reduced microbial exposure in early life and perturbation of the human microbiome composition. Increasing evidence shows that early life interactions between the human microbiome and the immune cells play a pivotal role in the development of the immune system. Therefore, the process of early colonization by a “healthy” microbiome is emerging as a key determinant of life-long health. In stark contrast, the perturbation of such a process, which results in changes in the host-microbiome biodiversity and metabolic activities, has been associated with greater susceptibility to immune-mediated disorders later in life, including allergic diseases. Here, we outline recent findings on the potential contribution of the microbiome in the gastrointestinal tract, skin, and airways to the development of FA, AD, and asthma. Furthermore, we address how the modulation of the microbiome composition in these different body districts could be a potential strategy for the prevention and treatment of allergic diseases.

22,080 views

104 citations