Infant Immune Development Research Articles

Higher maternal bread and thiamine intakes are associated with increased infant allergic disease.

A mother's diet during pregnancy may influence her infant's immune development. However, as potential interactions between components of our dietary intakes can make any nutritional analysis complex, here we took a multi-component dietary analysis approach. Nutritional intake data was collected from 639 pregnant women using a validated semi-quantitative food frequency questionnaire to reflect their dietary intakes during 32-36 weeks of gestation. To investigate their dietary intake pattern, we calculated Dietary Inflammatory Index scores. Maternal consumption of 12 food groups, 20 individual whole foods, and 18 specific nutrient intakes, along with any vitamin and mineral supplementation, were determined. Infant outcomes included eczema, allergen sensitization, and IgE-mediated food allergy. Regression-based analyses with covariates adjustment were applied. Women with higher white bread consumption were more likely to have an infant with doctor-diagnosed eczema (adjusted relative risk [aRR] 1.16; 95% CI 1.08, 1.24; p < .001) and IgE-mediated food allergy (aRR 1.14; 95% CI 1.02, 1.28; p = .02). Higher maternal intakes of fiber-rich bread (aRR 1.14; 95% CI 1.04, 1.25; p = .01) and legumes (aRR 1.11; 95% CI 1.02, 1.21; p = .02) were also associated with infant doctor-diagnosed eczema. Higher maternal thiamine intakes were associated with increased parent-reported infant eczema (aRR 1.08; 95% CI 1.03, 1.12; p < .001). In Australia, where bread flour is fortified with thiamine, we identified consistent links between higher maternal thiamine-rich diets and increased risk of infant eczema and food allergy. Our results highlight a need for further investigation of potential effects of high thiamine exposures on immune development, especially in-utero.

Effect of maternal prebiotic supplementation on human milk immunological composition: Insights from the SYMBA study.

Immunomodulatory proteins in human milk (HM) can shape infant immune development. However, strategies to modulate their levels are currently unknown. This study investigated whether maternal prebiotic supplementation alters the levels of immunomodulatory proteins in HM. The study was nested within the SYMBA double-blind randomized controlled trial (ACTRN12615001075572), which investigated the effects of maternal prebiotic (short-chain galacto-oligosaccharides/long-chain fructo-oligosaccharides) supplementation from <21 weeks gestation during pregnancy until 6 months postnatal during lactation on child allergic disease risk. Mother-child dyads receiving prebiotics (n = 46) or placebo (n = 54) were included in this study. We measured the levels of 24 immunomodulatory proteins in HM collected at 2, 4, and 6 months. Cluster analysis showed that the overall immunomodulatory protein composition of milk samples from both groups was similar. At 2 months, HM of prebiotic-supplemented women had decreased levels of TGF-β1 and TSLP (95% CI: -17.4 [-29.68, -2.28] and -57.32 [-94.22, -4.7] respectively) and increased levels of sCD14 (95% CI: 1.81 [0.17, 3.71]), when compared to the placebo group. At 4 months, IgG1 was lower in the prebiotic group (95% CI: -1.55 [-3.55, -0.12]) compared to placebo group. This exploratory study shows that prebiotic consumption by lactating mothers selectively alters specific immunomodulatory proteins in HM. This finding is crucial for understanding how prebiotic dietary recommendations for pregnant and lactating women can modify the immune properties of HM and potentially influence infant health outcomes through immune support from breastfeeding.

The Role of Breastfeeding in Acute Respiratory Infections in Infancy.

Acute respiratory infections (ARIs) affect the respiratory tract, are often caused by viruses such as respiratory syncytial virus and rhinovirus, and present symptoms such as coughing, fever, respiratory distress, and breathing difficulty. The global adherence to exclusive breastfeeding (BF) for the first 6 months of life has reached 44%, supported by the World Health Organization and United Nations International Children's Emergency Fund efforts. BF provides vital nutrients and contributes to infant immune system development, protecting against infections. The role of BF in preventing and reducing complications of ARIs in infants is gaining attention, prompting a review of current data and future research needs. This review aims to summarize the evidence on the role of BF in reducing the risk and severity of ARIs in infants, elucidate the adaptations in breast milk composition during infections, and identify relevant research needs. Human milk (HM) is rich in immunoglobulins, antimicrobial peptides, and immunomodulatory factors that protect against various pathogens, including respiratory viruses. Several studies have demonstrated that BF is associated with a significant reduction in hospitalization, oxygen requirements, and mortality in infants with ARIs. The effectiveness of BF varies according to the specific respiratory virus, and a longer duration of exclusive BF appears to enhance its protective effect. It is documented that the composition of HM adjusts dynamically in response to infections, fortifying the infant's immune defenses. Specific immunological components of HM, including leukocytes and immunoglobulins, increase in response to infection in the infant, contributing to the enhancement of the immune defense in infants. Immune-boosting microRNAs enhance immune transfer to the infants and promote early gut maturation, and the HM microbiome along with other factors modifies the infant's gut microbiome and immune system. BF defends infants from respiratory infections, and the investigation of the microRNAs in HM offers new insights into its antiviral properties. The promotion of BF, especially in vulnerable communities, is of paramount importance in alleviating the global burden of ARIs in infancy.

The evolving world of milk oligosaccharides: Biochemical diversity understood by computational advances

Milk oligosaccharides, complex carbohydrates unique to mammalian milk, play crucial roles in infant nutrition and immune development. This review explores their biochemical diversity, tracing the evolutionary paths that have led to their variation across different species. We highlight the intersection of nutrition, biology, and chemistry in understanding these compounds. Additionally, we discuss the latest computational methods and analytical techniques that have revolutionized the study of milk oligosaccharides, offering insights into their structural complexity and functional roles. This brief but essential review not only aims to provide a deeper understanding of milk oligosaccharides but also discuss the road toward their potential applications.

Mammary epithelium permeability during established lactation: associations with cytokine levels in human milk.

The cytokine profile of human milk may be a key indicator of mammary gland health and has been linked to infant nutrition, growth, and immune system development. The current study examines the extent to which mammary epithelium permeability (MEP) is associated with cytokine profiles during established lactation within a sample of US mothers. Participants were drawn from a previous study of human milk cytokines. The present analysis includes 162 participants (98 Black, 64 White) with infants ranging from 1 to 18 months of age. Levels of cytokines were determined previously. Here we measure milk sodium (Na) and potassium (K) levels with ion-selective probes. Two approaches were used to define elevated MEP: Na levels ≥10 mmol/L and Na/K ratios greater than 0.6. Associations between maternal-infant characteristics, elevated MEP, and twelve analytes (IL-6, IL-8, TNFα, IL-1β, FASL, VEGFD, FLT1, bFGF, PLGF, EGF, leptin, adiponectin) were examined using bivariate associations, principal components analysis, and multivariable logistic regression models. Elevated MEP was observed in 12 and 15% of milk samples as defined by Na and Na/K cutoffs, respectively. The odds of experiencing elevated MEP (defined by Na ≥ 10 mmol/L) were higher among Black participants and declined with older infant age. All cytokines, except leptin, were positively correlated with either Na or the Na/K ratio. A pro-inflammatory factor (IL-6, IL-8, TNFα, IL-1β, EGF) and a tissue remodeling factor (FASL, VEGFD, FLT1, bFGF, PLGF, adiponectin) each contributed uniquely to raising the odds of elevated MEP as defined by either Na or the Na/K ratio. This exploratory analysis of MEP and cytokine levels during established lactation indicates that elevated MEP may be more common in US populations than previously appreciated and that individuals identifying as Black may have increased odds of experiencing elevated MEP based on current definitions. Research aimed at understanding the role of MEP in mammary gland health or infant growth and development should be prioritized.

Particles in Raw Sheep Milk Can Modulate the Inflammatory Response in THP-1, a Human Monocyte Cell Line, In Vitro

Background: The UK dairy sheep industry is relatively small but growing, particularly for cheese and yogurt products. Anecdotally, sheep milk (SM) may be better tolerated by humans than cows’ milk and could have environmental as well as health benefits. All milk contains sub-micron particles called extracellular vesicles (EVs) which are mainly derived from the mammary epithelium. Physiologically, milk-derived EVs are thought to aid in the development of infant immunity and the microbiome, but may also have health benefits to adult humans. The purpose of this study was to determine whether EVs could be isolated from raw sheep milk and whether they have any effect on inflammatory responses in THP-1, a human monocyte cell line, in vitro. Methods: Using sequential ultracentrifugation, vesicles of &lt;1 µm (LEV) followed by &lt;200 nm (sEVs) were isolated from six individual sheep during mid-lactation. RNA was extracted and microRNA analyzed by RTqPCR for sequences previously identified in cows’ milk. Human THP-1 monocytes were differentiated into macrophages and incubated with SM-derived LEVs and sEVs in the presence of pro-inflammatory LPS to measure the effects on the secretion of the chemokine CCL-2 or in the presence of DMNQ and fluorescent dihydrorhodamine-1,2,3 to measure reactive oxygen species. Results: LEVs induced an increase in ROS in both monocytes and macrophages, whilst sEVs decreased DMNQ-mediated ROS in macrophages but not monocytes. Interestingly, the LEVs did not induce CCL2 release; however, they increased LPS-induced CCL2 secretion in monocytes but not macrophages. miR26a, miR92a, miR125b, miR155 and miR223 were identified in both sEVs and LEVs by RT-qPCR and could be responsible for the modulation of ROS and CCL2 expression. Conclusions: These findings suggest that like cows’ milk, sheep milk contains EVs, and they can influence human monocyte/macrophage responses, and so is worthy of further investigation for its potential human- and non-human-animal health benefits.

Influence of technical and maternal-infant factors on the measurement and expression of extracellular miRNA in human milk.

Breast milk contains thousands of bioactive compounds including extracellular vesicle microRNAs (EV-miRNAs), which may regulate pathways such as infant immune system development and metabolism. We examined the associations between the expression of EV-miRNAs and laboratory variables (i.e., batch effects, sample characteristics), sequencing quality indicators, and maternal-infant characteristics. The study included 109 Latino mother-infant dyads from the Southern California Mother's Milk Study. Mothers were age 28.0 ± 5.6 and 23-46 days postpartum. We used principal components analysis to evaluate whether EV-miRNA expression was associated with factors of interest. Then, we used linear models to estimate relationships between these factors and specific EV-miRNA counts and analyzed functional pathways associated with those EV-miRNAs. Finally, we explored which maternal-infant characteristics predicted sequencing quality indicators. Sequencing quality indicators, predominant breastfeeding, and breastfeedings/day were associated with EV-miRNA principal components. Maternal body mass index and breast milk collection timing predicted proportion of unmapped reads. Expression of 2 EV-miRNAs were associated with days postpartum, 23 EV-miRNAs were associated with breast milk collection time, 23 EV-miRNAs were associated with predominant breastfeeding, and 38 EV-miRNAs were associated with breastfeedings/day. These EV-miRNAs were associated with pathways including Hippo signaling pathway and ECM-receptor interaction, among others. This study identifies several important factors that may contribute to breast milk EV-miRNA expression. Future studies should consider these findings in the design and analysis of breast milk miRNA research.

Biomarkers detected in cord blood predict vaccine responses in young infants.

Factors influencing vaccine immune priming in the first year of life involve both innate and adaptive immunity but there are gaps in understanding how these factors sustain vaccine antibody levels in healthy infants. The hypothesis was that bioprofiles associated with B cell survival best predict sustained vaccine IgG levels at one year. Longitudinal study of plasma bioprofiles in 82 term, healthy infants, who received standard recommended immunizations in the United States, with changes in 15 plasma biomarker concentrations and B cell subsets associated with germinal center development monitored at birth, soon after completion of the initial vaccine series at 6 months, and prior to the 12-month vaccinations. Post vaccination antibody IgG levels to Bordetella pertussis, tetanus toxoid, and conjugated Haemophilus influenzae type B (HiB) were outcome measures. Using a least absolute shrinkage and selection operator (lasso) regression model, cord blood (CB) plasma IL-2, IL-17A, IL-31, and soluble CD14 (sCD14) were positively associated with pertussis IgG levels at 12 months, while CB plasma concentrations of APRIL and IL-33 were negatively associated. In contrast, CB concentrations of sCD14 and APRIL were positively associated with sustained tetanus IgG levels. A separate cross-sectional analysis of 18 mother/newborn pairs indicated that CB biomarkers were not due to transplacental transfer, but rather due to immune activation at the fetal/maternal interface. Elevated percentages of cord blood switched memory B cells were positively associated with 12-month HiB IgG levels. BAFF concentrations at 6 and 12 months were positively associated with pertussis and HiB IgG levels respectively. Sustained B cell immunity is highly influenced by early life immune dynamics beginning prior to birth. The findings provide important insights into how germinal center development shapes vaccine responses in healthy infants and provide a foundation for studies of conditions that impair infant immune development.

In Vitro Infant Fecal Fermentation Characteristics of Human Milk Oligosaccharides Were Controlled by Initial Microbiota Composition More than Chemical Structure.

Human milk oligosaccharides (HMOs), multifunctional glycans naturally present in human milk, are known to contribute to the infant's microbiota and immune system development. However, the molecular specificity of HMOs on microbiota and associated fermentation is not yet fully understood, and is important for the development of infant formula optimum functionality. In vitro fermentation is carried out on structurally different HMOs with infant fecal inocula dominated by Bifidobacterium longum, Bifidobacterium breve, and Bacteroides. The gas, metabolite (SCFA, lactate, and succinate) profiles, and microbiota responses differ between individual microbiota inocula patterns regardless of HMO structure. In terms of HMO pairs with same sugar composition but different glycosidic bonds, gas and metabolite profiles are similar with the B. longum- and B. breve-dominated inocula. However, large individual variations are observed with the Bacteroides-dominated inocula. The microbial communities at the end of fermentation are closely related to the initial microbiota composition. The findings demonstrate that short-term in vitro fermentation outcomes largely depend on the initial gut microbiota composition more than the impact of HMO molecular specificity. These results advance the current understanding for the design of personalized infant nutritional solutions and therapies in future.

Biomarkers of Development of Immunity and Allergic Diseases in Farming and Non-farming Lifestyle Infants: Design, Methods and 1 Year Outcomes in the "Zooming in to Old Order Mennonites" Birth Cohort Study.

Traditional farming lifestyle has been shown to be protective against asthma and allergic diseases. The individual factors that appear to be associated with this “farm-life effect” include consumption of unpasteurized farm milk and exposure to farm animals and stables. However, the biomarkers of the protective immunity and those associated with early development of allergic diseases in infancy remain unclear. The “Zooming in to Old Order Mennonites (ZOOM)” study was designed to assess the differences in the lifestyle and the development of the microbiome, systemic and mucosal immunity between infants born to traditional farming lifestyle at low risk for allergic diseases and those born to urban/suburban atopic families with a high risk for allergic diseases in order to identify biomarkers of development of allergic diseases in infancy. 190 mothers and their infants born to Old Order Mennonite population protected from or in Rochester families at high risk for allergic diseases were recruited before birth from the Finger Lakes Region of New York State. Questionnaires and samples are collected from mothers during pregnancy and after delivery and from infants at birth and at 1–2 weeks, 6 weeks, 6, 12, 18, and 24 months, with 3-, 4-, and 5-year follow-up ongoing. Samples collected include maternal blood, stool, saliva, nasal and skin swabs and urine during pregnancy; breast milk postnatally; infant blood, stool, saliva, nasal and skin swabs. Signs and symptoms of allergic diseases are assessed at every visit and serum specific IgE is measured at 1 and 2 years of age. Allergic diseases are diagnosed by clinical history, exam, and sensitization by skin prick test and/or serum specific IgE. By the end of the first year of life, the prevalence of food allergy and atopic dermatitis were higher in ROC infants compared to the rates observed in OOM infants as was the number of infants sensitized to foods. These studies of immune system development in a population protected from and in those at risk for allergic diseases will provide critical new knowledge about the development of the mucosal and systemic immunity and lay the groundwork for future studies of prevention of allergic diseases.

Effect of Maternal HIV Infection on Infant Development and Outcomes

Early life represents a period of profound immunological development and heightened susceptibility to infectious disease. The developmental trajectory over this period is influenced by a number of factors, including gestational age, mode of delivery, mode of feeding, microbiome development, and environmental exposures. There are also several maternal factors that have been shown to have a negative effect on both immune development and clinical outcomes, including maternal infection and inflammation. Studies have associated maternal HIV infections with an increase in infectious morbidity and mortality and decreased growth measures among their HIV-exposed uninfected (HEU) offspring. Among HEU infants, socioeconomic factors, maternal nutrition, maternal viral load, and maternal inflammation have also all been associated with impaired infant immune status and clinical outcomes. However, the mechanisms underlying these observations have not been elucidated and, apart from measures of disease severity, few studies thus far have undertaken in-depth assessments of maternal health status or immune function during gestation and how these influence developmental outcomes in their infants. The lack of a mechanistic understanding of how these gestational influences affect infant outcomes inhibits the ability to design and implement effective interventions. This review describes the current state of research into these mechanisms and highlights areas for future study include; how HIV infection causes the inflammatory trajectory to deviate from normal gestation, the mechanism(s) by which in utero exposure to maternal inflammation influences infant immune development and clinical outcomes, the role of socioeconomic factors as an inducer of maternal stress and inflammation, and maternal nutrition during gestation.

Exposure to diverse microbial flora accelerates the development of infant immunity

Abstract The newborn immune system is considered underdeveloped and ill-equipped to defend itself against many pathogens. Indeed, infection is the leading cause of hospitalization and death for infants under 6 months. Relative to the adult immune system, little is known about infant immunity or the signals that orchestrate immunologic maturation. The constraints of human research and the use of sterile animal models limit advancements in this area. Commonly used animal models are raised in “specific pathogen free” (SPF) conditions to minimize the confounding effects of diverse microbial exposure. We sought to understand the physiologic effects of exposure to those diverse microbes on infant immune development. We co-housed laboratory mice with pet store mice from conception to expose them to diverse microbial flora. Microbial exposure led to a dramatic shift in immune cell composition with increases in the proportion of T cell memory, helper T cell subsets, macrophages, and neutrophils, as well as general increases in the number of most immune cell subsets as early as 2 weeks of age. The gap between the microbially-exposed mice and SPF mice continued to widen at 3 and 6 weeks of age. We also observed increased TNFα, IL-6, IL-5, IL-17, and RANTES expression at 3 weeks of age. By 6 weeks most of the cytokines/chemokines tested where increased. These observations demonstrate that exposure to diverse microbial flora during early life dramatically alters the trajectory of the developing immune system. A better understanding of how healthy immune systems develop, and the risks and benefits of modulating infant immunity could lead to important advancements in treatments for early life infection and novel infant vaccination approaches. Supported by Grants from: Medical School/University of Minnesota Foundation Award Program Masonic Cross-Departmental Grants in Children's Health Research University of Minnesota Department of Pediatrics "R" Award

Prevention of Atopic Dermatitis in Mice by Lactobacillus Reuteri Fn041 Through Induction of Regulatory T Cells and Modulation of the Gut Microbiota.

The development of atopic dermatitis (AD) in infants is closely related to the lagging development of intestinal microbiota, including that inoculated by breast milk bacteria, and immune development. Lactobacillus reuteri Fn041 is a secretory immunoglobulin A (sIgA) -coated bacterium derived from human milk. We intervene with L. reuteri Fn041 in maternal and offspring BALB/C mice during late gestation and lactation and after weaning of the pups, respectively. AD is then induced with MC903. L. reuteri Fn041 significantly suppresses AD symptoms such as skin swelling, mast cell, and eosinophil infiltration. This effect is attributed to the regulation of the systemic Th1 and Th2 cytokine ratios and the promotion of CD4+ CD25+ Foxp3+ regulatory T cell proliferation in mesenteric lymph nodes. It is also associated with the regulation of intestinal microbiota, particularly promoting Lactobacillus and Akkermansia. Our study strengthens the understanding that breast milk-derived sIgA coated potential probiotics are involved in the development of infant intestinal microbiota, thus promoting immune development and preventing allergic diseases, and expanding the knowledge of breast milk sIgA and bacterial interactions on infant immune development.

Widespread vertical transmission of secretory immunoglobulin A coated trace bacterial variants from the mother to infant gut through breastfeeding.

Gut microbiota transmission from mother to offspring is critical to infant gut microbiota and immune development. Mother's intestine and breast milk are rich in secretory immunoglobulin A (sIgA), which can coat a specific bacterial spectrum and may be related to bacterial transmission and colonization. Here we analyzed the microbiota and sIgA-coated bacteria of maternal fecal samples and breast milk and infant fecal samples from 19 dyads by 16S rRNA amplicon sequencing. For the sIgA-coated microbiota, both the phylogenetic diversity and the Shannon index of maternal fecal samples show a lower trend than those of infant fecal samples (P < 0.05). For beta diversity, all three samples were significantly different from each other (P < 0.05, based on permutational multivariate analysis of variance). We found that sIgA mediated a wide range of vertical transmission of trace bacteria with a relative abundance of amplicon sequence variants of more than 0.0001%. FEAST-based analysis reveals that there was an equal contribution of the maternal gut (median [IQR]; 8.75% [0.90, 62.14]) and breast milk (9.23% [1.69, 22.29]) to infant intestinal total microbiota. The 39 percent of sIgA-coated microbiota in breast milk samples provided as much as 28.49-93.84 percent of all sIgA-coated microbiota in the newborn gut. Therefore, maternal gut and breast milk sIgA-coated bacteria are essential sources of intestinal bacteria in infants. There was high individual variation in the contribution of the maternal gut and breast milk microbiota to the paired infant gut microbiota. Analysis based on the weighted transfer ratio (WTR) explained that diverse sIgA-coated bacteria are transferred from breast milk to the gut of the respective infant, mainly lactic acid bacteria, especially Lactobacillus gasseri (WTR = 2475.5), Enterococcus faecium (WTR = 2438) and Streptococcus salivarius (WTR = 117.71). Bifidobacterium longum, with a WTR of 69.35, is the key sIgA-coated bacteria that are transferred from the mother's gut to breast milk. In conclusion, sIgA mediates the vertical transmission of specific bacteria, to realize the controllable inheritance of the intestinal bacteria and function from the mother to the offspring. This provides a new basis for the screening of probiotics for infant formula addition.

Nurturing the Early Life Gut Microbiome and Immune Maturation for Long Term Health.

Early life is characterized by developmental milestones such as holding up the head, turning over, sitting up and walking that are typically achieved sequentially in specific time windows. Similarly, the early gut microbiome maturation can be characterized by specific temporal microorganism acquisition, colonization and selection with differential functional features over time. This orchestrated microbial sequence occurs from birth during the first years of age before the microbiome reaches an adult-like composition and function between 3 and 5 years of age. Increasingly, these different steps of microbiome development are recognized as crucial windows of opportunity for long term health, primarily linked to appropriate immune and metabolic development. For instance, microbiome disruptors such as preterm and Cesarean-section birth, malnutrition and antibiotic use are associated with increased risk to negatively affect long-term immune and metabolic health. Different age discriminant microbiome taxa and functionalities are used to describe age-appropriate microbiome development, and advanced modelling techniques enable an understanding and visualization of an optimal microbiome maturation trajectory. Specific microbiome features can be related to later health conditions, however, whether such features have a causal relationship is the topic of intense research. Early life nutrition is an important microbiome modulator, and ‘Mother Nature’ provides the model with breast milk as the sole source of nutrition for the early postnatal period, while dietary choices during the prenatal and weaning period are to a large extent guided by tradition and culture. Increasing evidence suggests prenatal maternal diet and infant and child nutrition impact the infant microbiome trajectory and immune competence development. The lack of a universal feeding reference for such phases represents a knowledge gap, but also a great opportunity to provide adequate nutritional guidance to maintain an age-appropriate microbiome for long term health. Here, we provide a narrative review and perspective on our current understanding of age-appropriate microbiome maturation, its relation to long term health and how nutrition shapes and influences this relationship.

Immunogenicity of an oral rotavirus vaccine administered with prenatal nutritional support in Niger: A cluster randomized clinical trial.

BackgroundNutritional status may play a role in infant immune development. To identify potential boosters of immunogenicity in low-income countries where oral vaccine efficacy is low, we tested the effect of prenatal nutritional supplementation on immune response to 3 doses of a live oral rotavirus vaccine.Methods and findingsWe nested a cluster randomized trial within a double-blind, placebo-controlled randomized efficacy trial to assess the effect of 3 prenatal nutritional supplements (lipid-based nutrient supplement [LNS], multiple micronutrient supplement [MMS], or iron–folic acid [IFA]) on infant immune response (n = 53 villages and 1,525 infants with valid serology results: 794 in the vaccine group and 731 in the placebo group). From September 2015 to February 2017, participating women received prenatal nutrient supplement during pregnancy. Eligible infants were then randomized to receive 3 doses of an oral rotavirus vaccine or placebo at 6–8 weeks of age (mean age: 6.3 weeks, 50% female). Infant sera (pre-Dose 1 and 28 days post-Dose 3) were analyzed for anti-rotavirus immunoglobulin A (IgA) using enzyme-linked immunosorbent assay (ELISA). The primary immunogenicity end point, seroconversion defined as ≥3-fold increase in IgA, was compared in vaccinated infants among the 3 supplement groups and between vaccine/placebo groups using mixed model analysis of variance procedures. Seroconversion did not differ by supplementation group (41.1% (94/229) with LNS vs. 39.1% (102/261) with multiple micronutrients (MMN) vs. 38.8% (118/304) with IFA, p = 0.91). Overall, 39.6% (n = 314/794) of infants who received vaccine seroconverted, compared to 29.0% (n = 212/731) of infants who received placebo (relative risk [RR]: 1.36; 95% confidence interval [CI]: 1.18, 1.57, p < 0.001). This study was conducted in a high rotavirus transmission setting. Study limitations include the absence of an immune correlate of protection for rotavirus vaccines, with the implications of using serum anti-rotavirus IgA for the assessment of immunogenicity and efficacy in low-income countries unclear.ConclusionsThis study showed no effect of the type of prenatal nutrient supplementation on immune response in this setting. Immune response varied depending on previous exposure to rotavirus, suggesting that alternative delivery modalities and schedules may be considered to improve vaccine performance in high transmission settings.Trial registrationClinicalTrials.gov NCT02145000.

Impact of dietary aflatoxin on immune development in Gambian infants: a cohort study

BackgroundChronic aflatoxin (AF) exposure has been shown to occur at high levels in children from sub-Saharan Africa (SSA), and has been associated with growth retardation and immune dysfunction. Our objective...

Human milk microbiome: From actual knowledge to future perspective

Human milk is the gold standard for infant nutrition during the first months of life since it is perfectly adapted to the neonatal nutritional requirements and supports infant growth and development. Human milk contains a complex nutritional and bioactive composition including microorganisms and oligosaccharides which would also contribute to the gut and immune system maturation. Despite the growing evidence, the factors contributing to milk microbes’ variations and the potential functions on the infant's gut are still uncovered. This short-review provides a general overview of milk microbiota, potential factors shaping its composition, contribution to the infant microbiota and immune system development, including the suggested biological relevance for infant health as well as the description of tools and strategies aimed to restore and module microbes in milk.

Amino Acid Formula Containing Synbiotics in Infants with Cow's Milk Protein Allergy: A Systematic Review and Meta-Analysis.

Cow’s milk protein allergy (CMPA) is associated with dysbiosis of the infant gut microbiome, with allergic and immune development implications. Studies show benefits of combining synbiotics with hypoallergenic formulae, although evidence has never been systematically examined. This review identified seven publications of four randomised controlled trials comparing an amino acid formula (AAF) with an AAF containing synbiotics (AAF-Syn) in infants with CMPA (mean age 8.6 months; 68% male, mean intervention 27.3 weeks, n = 410). AAF and AAF-Syn were equally effective in managing allergic symptoms and promoting normal growth. Compared to AAF, significantly fewer infants fed AAF-Syn had infections (OR 0.35 (95% CI 0.19–0.67), p = 0.001). Overall medication use, including antibacterials and antifectives, was lower among infants fed AAF-Syn. Significantly fewer infants had hospital admissions with AAF-Syn compared to AAF (8.8% vs. 20.2%, p = 0.036; 56% reduction), leading to potential cost savings per infant of £164.05–£338.77. AAF-Syn was associated with increased bifidobacteria (difference in means 31.75, 95% CI 26.04–37.45, p < 0.0001); reduced Eubacterium rectale and Clostridium coccoides (difference in means −19.06, 95% CI −23.15 to −14.97, p < 0.0001); and reduced microbial diversity (p < 0.05), similar to that described in healthy breastfed infants, and may be associated with the improved clinical outcomes described. This review provides evidence that suggests combining synbiotics with AAF produces clinical benefits with potential economic implications.

Crosstalk between sIgA-Coated Bacteria in Infant Gut and Early-Life Health.

Gut microbiota transmission from mother to offspring has attracted much interest in recent years. The gut microbiota in the infant plays a potentially significant role in modulating and maintaining the development of infant immunity. Secretory immunoglobulin A (sIgA), the major immunoglobulin in the intestine, can target polysaccharides and flagellin on the bacterial surface, resulting in sIgA-coated bacteria. The presentation of specific bacteria coated with sIgA may be a signal of disease and provide novel insights into the relationship between infant microbiota and disease. Here, we review the composition of sIgA-coated bacteria in the adult intestine, human milk, and the infant intestine, as well as the factors that influence the development of gut microbiota in early life. Then, we highlight the diseases that are related to variations in sIgA-coated bacteria in the infant and adult intestine. Furthermore, we discuss the possibility that sIgA-coated bacteria could play a role in mediating both innate and adaptive immune responses. Finally, we propose directions for future research to promote our understanding within this field.