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BACKGROUND: Alongside microbiota development, the evolution of the resistome is crucial in understanding the early-life acquisition and persistence of Antibiotic Resistance Genes (ARGs). Therefore, the aim of this study is to provide a comprehensive view of the evolution and dynamics of the neonatal resistome from 7 days to 4 months of age using a high-throughput qPCR platform. METHODS: In the initial phase, a massive screening of 384 ARGs using a high-throughput qPCR in pooled healthy mother-infant pairs feces from the MAMI cohort was carried out to identify the most abundant and prevalent ARGs in infants and in mothers. This pre-analysis allowed for later targeted profiling in a large number of infants in a longitudinal manner during the first 4 months of life. 16S rRNA V3-V4 amplicon sequencing was performed to asses microbial composition longitudinally. Potential factors influencing the microbiota and ARGs in this period were also considered, such as mode of birth and breastfeeding type. RESULTS: Following the massive screening, the top 45 abundant ARGs and mobile genetic elements were identified and studied in 72 infants during their first months of life (7 days, 1, 2, and 4 months). These genes were associated with resistance to aminoglycosides, beta-lactams and tetracyclines, among others, as well as integrons, and other mobile genetic elements. Changes in both ARG composition and quantity were observed during the first 4 months of life: most ARGs abundance increased over time, but mobile genetic elements decreased significantly. Further exploration of modulating factors highlighted the effect on ARG composition of specific microbial genus, and the impact of mode of birth at 7 days and 4 months. The influence of infant formula feeding was observed at 4-month-old infants, who exhibited a distinctive resistome composition. CONCLUSIONS: This study illustrates the ARG evolution and dynamics in the infant gut by use of a targeted, high-throughput, quantitative PCR-based method. An increase in antibiotic resistance over the first months of life were observed with a fundamental role of delivery mode in shaping resistance profiles. Further, we highlighted the influence of feeding methods on the resistome development. These findings offer pivotal insights into dynamics of and factors influencing early-life resistome, with potential avenues for intervention strategies.
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Antibacterianos , Heces , Microbioma Gastrointestinal , ARN Ribosómico 16S , Humanos , Microbioma Gastrointestinal/efectos de los fármacos , Microbioma Gastrointestinal/genética , Lactante , Recién Nacido , Heces/microbiología , Femenino , Antibacterianos/farmacología , ARN Ribosómico 16S/genética , Masculino , Lactancia Materna , Bacterias/genética , Bacterias/efectos de los fármacos , Bacterias/clasificación , Genes Bacterianos/genética , Farmacorresistencia Bacteriana/genética , Evolución Molecular , Farmacorresistencia Microbiana/genética , Estudios LongitudinalesRESUMEN
Introduction: Maternal synbiotic supplementation during pregnancy and lactation can significantly influence the immune system. Prebiotics and probiotics have a positive impact on the immune system by preventing or ameliorating among others intestinal disorders. This study focused on the immunomodulatory effects of B. breve M-16V and short chain galacto-oligosaccharides (scGOS)/long chain fructo-oligosachairdes (lcFOS), including systemic and mucosal compartments and milk composition. Methods: Lewis rats were orally administered with the synbiotic or vehicle during pregnancy (21 days) and lactation (21 days). At the weaning day, small intestine (SI), mammary gland (MG), adipose tissue, milk, mesenteric lymph nodes (MLN), salivary gland (SG), feces and cecal content were collected from the mothers. Results: The immunoglobulinome profile showed increased IgG2c in plasma and milk, as well as elevated sIgA in feces at weaning. The supplementation improved lipid metabolism through enhanced brown adipose tissue activity and reinforced the intestinal barrier by increasing the expression of Muc3, Cldn4, and Ocln. The higher production of short chain fatty acids in the cecum and increased Bifidobacterium counts suggest a potential positive impact on the gastrointestinal tract. Discussion: These findings indicate that maternal synbiotic supplementation during gestation and lactation improves their immunological status and improved milk composition.
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Bifidobacterium breve , Lactancia , Leche , Oligosacáridos , Animales , Femenino , Embarazo , Bifidobacterium breve/inmunología , Leche/inmunología , Leche/química , Ratas , Ratas Endogámicas Lew , Suplementos Dietéticos , Simbióticos/administración & dosificación , Probióticos/administración & dosificación , Probióticos/farmacologíaRESUMEN
Given that the host-microbe interaction is shaped by the immune system response, it is important to understand the key immune system-microbiota relationship during the period from conception to the first years of life. The present work summarizes the available evidence concerning human reproductive microbiota, and also, the microbial colonization during early life, focusing on the potential impact on infant development and health outcomes. Furthermore, we conclude that some dietary strategies including specific probiotics and other-biotics could become potentially valuable tools to modulate the maternal-neonatal microbiota during this early critical window of opportunity for targeted health outcomes throughout the entire lifespan.
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Microbiota , Probióticos , Humanos , Lactante , Recién Nacido , Femenino , Microbiota/fisiología , Microbiota/inmunología , Embarazo , Microbioma Gastrointestinal/inmunología , Microbioma Gastrointestinal/fisiología , Desarrollo Infantil/fisiología , Interacciones Microbiota-Huesped/inmunología , Interacciones Microbiota-Huesped/fisiologíaRESUMEN
Immunonutrition, which focuses on specific nutrients in breast milk and post-weaning diets, plays a crucial role in supporting infants' immune system development. This study explored the impact of maternal supplementation with Bifidobacterium breve M-16V and a combination of short-chain galacto-oligosaccharide (scGOS) and long-chain fructo-oligosaccharide (lcFOS) from pregnancy through lactation, extending into the early childhood of the offspring. The synbiotic supplementation's effects were examined at both mucosal and systemic levels. While the supplementation did not influence their overall growth, water intake, or food consumption, a trophic effect was observed in the small intestine, enhancing its weight, length, width, and microscopic structures. A gene expression analysis indicated a reduction in FcRn and Blimp1 and an increase in Zo1 and Tlr9, suggesting enhanced maturation and barrier function. Intestinal immunoglobulin (Ig) A levels remained unaffected, while cecal IgA levels decreased. The synbiotic supplementation led to an increased abundance of total bacteria and Ig-coated bacteria in the cecum. The abundance of Bifidobacterium increased in both the intestine and cecum. Short-chain fatty acid production decreased in the intestine but increased in the cecum due to the synbiotic supplementation. Systemically, the Ig profiles remained unaffected. In conclusion, maternal synbiotic supplementation during gestation, lactation, and early life is established as a new strategy to improve the maturation and functionality of the gastrointestinal barrier. Additionally, it participates in the microbiota colonization of the gut, leading to a healthier composition.
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INTRODUCTION: Probiotics have shown potential in reducing the occurrence of atopic eczema in high-risk infants. We aimed here to assess whether the preventive effect of maternal probiotic administration stems from compositional changes in early gut microbiota. METHODS: This study included 46 mother-infant pairs from an original randomized controlled trial assessing the impact of maternal probiotic intervention with either the combinations of Lacticaseibacillus rhamnosus LPR and Bifidobacterium longum BL999, or Lacticaseibacillus paracasei ST11 and Bifidobacterium longum BL999, or placebo beginning 2 months before expected delivery and ending 2 months after birth. All children were vaginally delivered, full term and breastfed. During the 2-year follow-up period, the children were clinically evaluated by physicians for atopic eczema, and their gut microbiota was profiled at 1 and 6 months of age by 16S rRNA gene sequencing using an Illumina sequencing platform. RESULTS: Altogether, 19 of 46 children developed atopic eczema by the age of 2 years. At 1 and 6 months of age, gut microbial diversity was similar between children who developed atopic eczema and their healthy controls, but at the age of 6 months, children who developed atopic eczema manifested with significantly higher relative abundance of Clostridia. Probiotic intervention did not significantly influence microbial diversity, and the effects on microbial composition were not consistent with the changes associated with the development of atopic eczema. CONCLUSION: The reduction of the risk of atopic eczema achieved by perinatal maternal probiotic intervention does not seem to require substantial gut microbiota modulation.
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BACKGROUND: Animal and human studies indicate that exposure to air pollution and natural environments might modulate the gut microbiota, but epidemiological evidence is very scarce. OBJECTIVES: To assess the potential impact of pre- and postnatal exposure to air pollution and green spaces on infant gut microbiota assembly and trajectories during the first year of life. METHODS: MAMI ("MAternal MIcrobes") birth cohort (Valencia, Spain, N = 162) was used to study the impact of environmental exposure (acute and chronic) on infant gut microbiota during the first year of life (amplicon-based 16S rRNA sequencing). At 7 days and at 1, 6 and 12 months, residential pre- and postnatal exposure to air pollutants (NO2, black carbon -BC-, PM2.5 and O3) and green spaces indicators (NDVI and area of green spaces at 300, 500 and 1000 m buffers) were obtained. For the association between exposures and alpha diversity indicators linear regression models (cross-sectional analyses) and mixed models, including individual as a random effect (longitudinal analyses), were applied. For the differential taxon analysis, the ANCOM-BC package with a log count transformation and multiple-testing corrections were used. RESULTS: Acute exposure in the first week of life and chronic postnatal exposure to NO2 were associated with a reduction in microbial alpha diversity, while the effects of green space exposure were not evident. Acute and chronic (prenatal or postnatal) exposure to NO2 resulted in increased abundance of Haemophilus, Akkermansia, Alistipes, Eggerthella, and Tyzerella populations, while increasing green space exposure associated with increased Negativicoccus, Senegalimassilia and Anaerococcus and decreased Tyzzerella and Lachnoclostridium populations. DISCUSSION: We observed a decrease in the diversity of the gut microbiota and signs of alteration in its composition among infants exposed to higher levels of NO2. Increasing green space exposure was also associated with changes in gut microbial composition. Further research is needed to confirm these findings.
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Contaminación del Aire , Microbioma Gastrointestinal , Microbioma Gastrointestinal/efectos de los fármacos , Humanos , Femenino , Lactante , España , Contaminación del Aire/efectos adversos , Recién Nacido , Contaminantes Atmosféricos/análisis , Contaminantes Atmosféricos/toxicidad , Cohorte de Nacimiento , Masculino , Exposición a Riesgos Ambientales/efectos adversos , Embarazo , Estudios de Cohortes , Exposición Materna/efectos adversos , Efectos Tardíos de la Exposición Prenatal/microbiologíaRESUMEN
The composition and maturation of the early-life microbiota are modulated by a number of perinatal factors, whose interplay in relation to microbial vertical transmission remains inadequately elucidated. Using recent strain-tracking methodologies, we analyzed mother-to-infant microbiota transmission in two different birth environments: hospital-born (vaginal/cesarean) and home-born (vaginal) infants and their mothers. While delivery mode primarily explains initial compositional differences, place of birth impacts transmission timing-being early in homebirths and delayed in cesarean deliveries. Transmission patterns vary greatly across species and birth groups, yet certain species, like Bifidobacterium longum, are consistently vertically transmitted regardless of delivery setting. Strain-level analysis of B. longum highlights relevant and consistent subspecies replacement patterns mainly explained by breastfeeding practices, which drive changes in human milk oligosaccharide (HMO) degrading capabilities. Our findings highlight how delivery setting, breastfeeding duration, and other lifestyle preferences collectively shape vertical transmission, impacting infant gut colonization during early life.
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Lactancia Materna , Leche Humana , Humanos , Femenino , Leche Humana/microbiología , Recién Nacido , Lactante , Microbioma Gastrointestinal/fisiología , Microbiota/fisiología , Adulto , Bifidobacterium , Transmisión Vertical de Enfermedad Infecciosa , EmbarazoRESUMEN
Immune system development during gestation and suckling is significantly modulated by maternal environmental and dietary factors. Breastfeeding is widely recognized as the optimal source of nutrition for infant growth and immune maturation, and its composition can be modulated by the maternal diet. In the present work, we investigated whether oral supplementation with Bifidobacterium breve M-16V and short-chain galacto-oligosaccharide (scGOS) and long-chain fructo-oligosaccharide (lcFOS) to rat dams during gestation and lactation has an impact on the immune system and microbiota composition of the offspring at day 21 of life. On that day, blood, adipose tissue, small intestine (SI), mesenteric lymph nodes (MLN), salivary gland (SG), cecum, and spleen were collected. Synbiotic supplementation did not affect the overall body or organ growth of the pups. The gene expression of Tlr9, Muc2, IgA, and Blimp1 were upregulated in the SI, and the increase in IgA gene expression was further confirmed at the protein level in the gut wash. Synbiotic supplementation also positively impacted the microbiota composition in both the small and large intestines, resulting in higher proportions of Bifidobacterium genus, among others. In addition, there was an increase in butanoic, isobutanoic, and acetic acid concentrations in the cecum but a reduction in the small intestine. At the systemic level, synbiotic supplementation resulted in higher levels of immunoglobulin IgG2c in plasma, SG, and MLN, but it did not modify the main lymphocyte subsets in the spleen and MLN. Overall, synbiotic maternal supplementation is able to positively influence the immune system development and microbiota of the suckling offspring, particularly at the gastrointestinal level.
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Animales Lactantes , Bifidobacterium breve , Suplementos Dietéticos , Microbioma Gastrointestinal , Oligosacáridos , Simbióticos , Animales , Simbióticos/administración & dosificación , Femenino , Embarazo , Ratas , Fenómenos Fisiologicos Nutricionales Maternos , Lactancia , Sistema Inmunológico , Masculino , Animales Recién NacidosRESUMEN
The early gut microbiota composition is fundamentally important for piglet health, affecting long-term microbiome development and immunity. In this study, the gut microbiota of postparturient dams was compared with that of their offspring in three Finnish pig farms at three growth phases. The differences in fecal microbiota of three study development groups (Good, Poorly, and PrematureDeath) were analyzed at birth (initial exposure phase), weaning (transitional phase), and before slaughter (stable phase). Dam Lactobacillaceae abundance was lower than in piglets at birth. Limosilactobacillus reuteri and Lactobacillus amylovorus were dominantly expressed in dams and their offspring. Altogether 17 piglets (68%) were identified with Lactobacillaceae at the initial exposure phase, divided unevenly among the development groups: 85% of Good, 37.5% of Poorly, and 75% of PrematureDeath pigs. The development group Good was identified with the highest microbial diversity, whereas the development group PrematureDeath had the lowest diversity. After weaning, the abundance and versatility of Lactobacillaceae in piglets diminished, shifting towards the microbiome of the dam. In conclusion, the fecal microbiota of pigs tends to develop towards a similar alpha and beta diversity despite development group and rearing environment.
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Heces , Microbioma Gastrointestinal , Destete , Animales , Heces/microbiología , Porcinos/microbiología , Porcinos/crecimiento & desarrollo , Femenino , Lactobacillaceae/crecimiento & desarrollo , Lactobacillaceae/genética , ARN Ribosómico 16S/genéticaRESUMEN
Growing evidence indicates that gut and respiratory microbiota have a potential key effect on bronchiolitis, mainly caused by respiratory syncytial virus (RSV). This was a prospective study of 96 infants comparing infants with bronchiolitis (n = 57, both RSV and non-RSV associated) to a control group (n = 39). Gut (feces) and respiratory [nasopharyngeal aspirate (NPA)] microbial profiles were analyzed by 16S rRNA amplicon sequencing, and respiratory viruses were identified by PCR. Clinical data of the acute episode and follow-up during the first year after infection were recorded. Pairwise comparisons showed significant differences in the gut (R2 = 0.0639, P = 0.006) and NPA (R2 = 0.0803, P = 0.006) microbiota between cases and controls. A significantly lower gut microbial richness and an increase in the NPA microbial diversity (mainly due to an increase in Haemophilus, Streptococcus, and Neisseria) were observed in the infants with bronchiolitis, in those with the most severe symptoms, and in those who subsequently developed recurrent wheezing episodes after discharge. In NPA, the higher microbial richness differed significantly between the control group and the non-RSV bronchiolitis group (P = 0.01) and between the control group and the RSV bronchiolitis group (P = 0.001). In the gut, the richness differed significantly between the control group and the non-RSV group (P = 0.01) and between the control group and the RSV bronchiolitis group (P = 0.001), with higher diversity in the RSV group. A distinct respiratory and intestinal microbial pattern was observed in infants with bronchiolitis compared with controls. The presence of RSV was a main factor for dysbiosis. Lower gut microbial richness and increased respiratory microbial diversity were associated with respiratory morbidity during follow-up. IMPORTANCE: Both the intestinal and respiratory microbiota of children with bronchiolitis, especially those with respiratory syncytial virus infection, are altered and differ from that of healthy children. The microbiota pattern in the acute episode could identify those children who will later have other respiratory episodes in the first year of life. Preventive measures could be adopted for this group of infants.
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Bronquiolitis , Microbioma Gastrointestinal , Infecciones por Virus Sincitial Respiratorio , Humanos , Lactante , Bronquiolitis/microbiología , Bronquiolitis/virología , Masculino , Femenino , Estudios Prospectivos , Infecciones por Virus Sincitial Respiratorio/microbiología , Infecciones por Virus Sincitial Respiratorio/virología , ARN Ribosómico 16S/genética , Bacterias/clasificación , Bacterias/aislamiento & purificación , Bacterias/genética , Recién Nacido , Heces/microbiología , Heces/virología , Microbiota , Hospitalización , Sistema Respiratorio/microbiología , Sistema Respiratorio/virología , Nasofaringe/microbiología , Nasofaringe/virología , Índice de Severidad de la EnfermedadRESUMEN
Resistance to antibiotics in newborns is a huge concern as their immune system is still developing, and infections and resistance acquisition in early life have short- and long-term consequences for their health. Bifidobacterium species are important commensals capable of dominating the infant gut microbiome and are known to be less prone to possess antimicrobial resistance genes than other taxa that may colonize infants. We aimed to study the association between Bifidobacterium-dominated infant gut microbiota and the antibiotic resistant gene load in neonates, and to ascertain the perinatal factors that may contribute to the antibiotic resistance acquisition. Two hundred infant fecal samples at 7 days and 1 month of age from the MAMI birth cohort were included in the study and for whom maternal-neonatal clinical records were available. Microbiota profiling was carried out by 16S rRNA amplicon sequencing, and targeted antibiotic resistance genes (ARGs) including tetM, tetW, tetO, blaTEM, blaSHV and ermB were quantified by qPCR. Infant microbiota clustered into two distinct groups according to their Bifidobacterium genus abundance: high and low. The main separation of groups or clusters at each time point was performed with an unsupervised non-linear algorithm of k-means partitioning to cluster data by time points based on Bifidobacterium genus relative abundance. Microbiota composition differed significantly between both groups, and specific bifidobacterial species were enriched in each cluster. Lower abundance of Bifidobacterium in the infant gut was associated with a higher load of antibiotic resistance genes. Our results highlight the relevance of Bifidobacterium genus in the early acquisition and establishment of antibiotic resistance in the gut. Further studies are needed to develop strategies to promote a healthy early colonization and fight against the spread of antibiotic resistances.
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Antibacterianos , Bifidobacterium , Farmacorresistencia Bacteriana , Heces , Microbioma Gastrointestinal , ARN Ribosómico 16S , Humanos , Bifidobacterium/genética , Bifidobacterium/efectos de los fármacos , Bifidobacterium/aislamiento & purificación , Recién Nacido , Microbioma Gastrointestinal/efectos de los fármacos , Heces/microbiología , Antibacterianos/farmacología , Femenino , ARN Ribosómico 16S/genética , Farmacorresistencia Bacteriana/genética , Masculino , LactanteRESUMEN
Manipulative behaviour that consists of touching or close contact with ears or tails of pen mates is common in pigs and can become damaging. Manipulative behaviour was analysed from video recordings of 45-day-old pigs, and 15 manipulator-control pairs (n = 30) were formed. Controls neither received nor performed manipulative behaviour. Rectal faecal samples of manipulators and controls were compared. 16S PCR was used to identify Lactobacillaceae species and 16S amplicon sequencing to determine faecal microbiota composition. Seven culturable Lactobacillaceae species were identified in control pigs and four in manipulator pigs. Manipulators (p = 0.02) and females (p = 0.005) expressed higher Lactobacillus amylovorus, and a significant interaction was seen (sex * status: p = 0.005) with this sex difference being more marked in controls. Females (p = 0.08) and manipulator pigs (p = 0.07) tended to express higher total Lactobacillaceae. A tendency for an interaction was seen in Limosilactobacillus reuteri (sex * status: p = 0.09). Results suggest a link between observed low diversity in Lactobacillaceae and the development of manipulative behaviour.
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Lactobacillaceae , Recto , Porcinos , Femenino , Masculino , Animales , HecesRESUMEN
Background: Maternal diet during pregnancy may play a role in infant health outcomes via the maternal microbiota. We assessed the association of the maternal diet index for the Mediterranean area (MDI-med) with infant gut microbiota at 1 month of life. Methods: The MAMI study is a longitudinal birth cohort in the Mediterranean area. In this work, a cross-sectional study, including 120 mother-infant dyads with available maternal diet and infant microbiota at 1-month-old data, was undertaken. The MDI developed in the US (MDI-US) was adapted for the MAMI cohort (MDI-med). Stratification based on extreme values resulted (22 in the "lower" MDI-med group and 23 in the "upper" group from the mean). Relative microbial abundances and alpha (microbial richness and diversity indexes) and beta diversity (Bray-Curtis distance matrix) were compared between the groups. Results: Higher maternal daily vegetable intake and lower red meat intake were the characteristics of the "upper" MDI-med group. Significantly lower microbial diversity (Shannon and InvSimpson index (p = 0.01)), but no changes in richness (Chao1 index) nor in beta-diversity, using Bray-Curtis distance, were observed in the "upper" group, compared to the "lower" MDI-med group. A higher relative abundance of the Bifidobacterium genus (Actinomycetota phylum) was associated with maternal daily vegetable and yogurt intake. Conclusion: Reduced infant microbial diversity at 1 month of age was associated with "upper" MDI-med scores. Higher maternal intakes of vegetables and yogurt were associated with higher relative abundances of the Bifidobacterium genus in the infant gut. Further studies are needed to understand the link between pregnancy diet, infant microbiota, and health outcomes.
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Cohorte de Nacimiento , Microbiota , Lactante , Embarazo , Femenino , Humanos , Estudios Transversales , Dieta , Madres , Verduras , BifidobacteriumRESUMEN
The gut microbiome has important roles in host metabolism and immunity, and microbial dysbiosis affects human physiology and health. Maternal immunity and microbial metabolites during pregnancy, microbial transfer during birth, and transfer of immune factors, microorganisms and metabolites via breastfeeding provide critical sources of early-life microbial and immune training, with important consequences for human health. Only a few studies have directly examined the interactions between the gut microbiome and the immune system during pregnancy, and the subsequent effect on offspring development. In this Review, we aim to describe how the maternal microbiome shapes overall pregnancy-associated maternal, fetal and early neonatal immune systems, focusing on the existing evidence and highlighting current gaps to promote further research.
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Microbioma Gastrointestinal , Microbiota , Embarazo , Femenino , Recién Nacido , Humanos , Microbioma Gastrointestinal/fisiología , Sistema Inmunológico , Lactancia MaternaRESUMEN
BACKGROUND: Children with cystic fibrosis (CF) present with gut dysbiosis, and current evidence impedes robust recommendations on the use of prebiotics. This study aimed at establishing the prebiotic potential of a commercial beta-glucan on the in vitro colonic microbiota of a child with CF compared to a healthy counterpart (H). METHODS: A dynamic simulator of colonic fermentation (twin-SHIME® model) was set up including the simulation of the proximal (PC) and distal colon (DC) of the CF and the H subjects by colonizing the bioreactors with faecal microbiota. During two weeks the system was supplied with the beta-glucan. At baseline, during treatment and post-treatment, microbiota composition was profiled by 16 S rRNA and short-chain fatty acids (SCFA) production was determined by GS-MS. RESULTS: At baseline, Faecalibacterium, was higher in CF' DC than in the H, along higher Acidaminococcus and less Megasphaera and Sutterella. Beta-glucan supplementation induced increased microbiota richness and diversity in both subjects during the treatment. At genus level, Pseudomonas and Veillonella decreased, while Akkermansia and Faecalibacterium increased significantly in CF. CONCLUSION: The supplementation with beta-glucan suggests positive results on CF colonic microbiota in the in vitro context, encouraging further research in the in vivo setting. IMPACT: Current evidence supports assessing the effect of prebiotics on modifying cystic fibrosis microbiota. The effect of beta-glucan supplementation was evaluated in a controlled dynamic in vitro colonic ecosystem. Beta-glucan supplement improved diversity in cystic fibrosis colonic microbiota. The treatment showed increased abundance of Faecalibacterium and Akkermansia in cystic fibrosis. New evidence supports the use of prebiotics in future clinical studies.
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Background: Breast milk is a complex and dynamic fluid needed for infant development and protection due to its content of bioactive factors such as immunoglobulins (Igs). Most studies focus primarily on IgA, but other types of Ig and even other immune components (cytokines and adipokines) may also play significant roles in neonatal health. As a first step, we aimed to characterize the Ig profile, many cytokines, and two adipokines (leptin and adiponectin) at two sampling time points within the transitional stage, which is the least studied phase in terms of these components. The secondary objective was to identify different breast milk immunotypes in the MAMI cohort substudy, and finally, we further aimed at analyzing maternal and infant characteristics to identify influencing factors of breast milk immune composition. Methods: Breast milk samples from 75 mothers were studied between days 7 and 15 postpartum. The Igs, cytokines, and adipokine levels were determined by a multiplex approach, except for the IgA, IgM, and leptin that were evaluated by ELISA. Results: IgA, IgM, IgE, IgG2, IL-1ß, IL-5, IL-6, IL-10, and IL-17 were significantly higher on day 7 with respect to day 15. The multiple factor analysis (MFA) allowed us to identify two maternal clusters (immunotypes) depending on the breast milk immune profile evolution from day 7 to day 15, mainly due to the IgE and IgG subtypes, but not for IgA and IgM, which always presented higher levels early in time. Conclusion: All these results demonstrated the importance of the dynamics of the breast milk composition in terms of immune factors because even in the same lactation stage, a difference of 1 week has induced changes in the breast milk immune profile. Moreover, this immune profile does not evolve in the same way for all women. The dynamic compositional changes may be maternal-specific, as we observed differences in parity and exclusive breastfeeding between the two BM immunotype groups, which could potentially impact infant health.
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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.
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Microbioma Gastrointestinal , MicroARNs , Femenino , Humanos , Lactante , Dieta , Microbioma Gastrointestinal/genética , Lactancia , MicroARNs/genética , Leche Humana/metabolismo , Nutrientes , Proteínas de Plantas , ARN Ribosómico 16S/genéticaRESUMEN
In this work, aqueous extracts from six different Pleurotus species were obtained and their yield, gross composition, ß-glucan content, monosaccharide profile, thermal stability, molecular weight distribution, and FT-IR were analyzed before and after purification through ethanol precipitation of the carbohydrate-rich fractions. The bioactivity (anti-inflammatory and immunomodulatory activity) of the various fractions obtained was also analyzed in three different cell cultures and compared with a lentinan control. The trend observed after purification of the aqueous fractions was an increase in the concentration of polysaccharides (especially ß-glucans), a decrease in ash, glucosamine and protein content and the elimination of low molecular weight (Mw) compounds, thus leaving in the purified samples high Mw populations with increased thermal stability. Interestingly, all these purified fractions displayed immunomodulatory capacity when tested in THP-1 macrophages and most of them also showed significant activity in HEK-hTLR4 cells, highlighting the bioactivity observed for Pleurotus ostreatus (both the extracts obtained from the whole mushroom and from the stipes). This specific species was richer in heteropolysaccharides, having moderate ß-glucan content and being enriched upon purification in a high Mw fraction with good thermal stability.