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OBJECTIVES: Breastfeeding is an energetically costly and intense form of human parental investment, providing sole-source nutrition in early infancy and bioactive components, including immune factors. Given the energetic cost of lactation, milk factors may be subject to tradeoffs, and variation in concentrations have been explored utilizing the Trivers-Willard hypothesis. As human milk immune factors are critical to developing immune system and protect infants against pathogens, we tested whether concentrations of milk immune factors (IgA, IgM, IgG, EGF, TGFß2, and IL-10) vary in response to infant sex and maternal condition (proxied by maternal diet diversity [DD] and body mass index [BMI]) as posited in the Trivers-Willard hypothesis and consider the application of the hypothesis to milk composition. METHODS: We analyzed concentrations of immune factors in 358 milk samples collected from women residing in 10 international sites using linear mixed-effects models to test for an interaction between maternal condition, including population as a random effect and infant age and maternal age as fixed effects. RESULTS: IgG concentrations were significantly lower in milk produced by women consuming diets with low diversity with male infants than those with female infants. No other significant associations were identified. CONCLUSIONS: IgG concentrations were related to infant sex and maternal diet diversity, providing minimal support for the hypothesis. Given the lack of associations across other select immune factors, results suggest that the Trivers-Willard hypothesis may not be broadly applied to human milk immune factors as a measure of maternal investment, which are likely buffered against perturbations in maternal condition.
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Leite Humano , Estado Nutricional , Feminino , Lactente , Masculino , Humanos , Lactação/fisiologia , Aleitamento Materno , Fatores Imunológicos , Imunoglobulina GRESUMO
Because breastfeeding provides optimal nutrition and other benefits for infants (e.g., lower risk of infectious disease) and benefits for mothers (e.g., less postpartum bleeding), many organizations recommend that healthy infants be exclusively breastfed for 4 to 6 months in the United States and 6 months internationally. Recommendations related to how long breastfeeding should continue, however, are inconsistent. The objective of this article is to review the literature related to evidence for benefits of breastfeeding beyond 1 year for mothers and infants. In summary, human milk represents a good source of nutrients and immune components beyond 1 year. Some studies point toward lower infant mortality in undernourished children breastfed for >1 year, and prolonged breastfeeding increases interbirth intervals. Data on other outcomes (e.g., growth, diarrhea, obesity, and maternal weight loss) are inconsistent, often lacking sufficient control for confounding variables. There is a substantial need for rigorous, prospective, mixed-methods, cross-cultural research on this topic.
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Aleitamento Materno , Estado Nutricional , Criança , Feminino , Humanos , Lactente , Obesidade , Estudos Prospectivos , Estados UnidosRESUMO
The novel coronavirus SARS-CoV-2 has emerged as one of the most compelling and concerning public health challenges of our time. To address the myriad issues generated by this pandemic, an interdisciplinary breadth of research, clinical and public health communities has rapidly engaged to collectively find answers and solutions. One area of active inquiry is understanding the mode(s) of SARS-CoV-2 transmission. Although respiratory droplets are a known mechanism of transmission, other mechanisms are likely. Of particular importance to global health is the possibility of vertical transmission from infected mothers to infants through breastfeeding or consumption of human milk. However, there is limited published literature related to vertical transmission of any human coronaviruses (including SARS-CoV-2) via human milk and/or breastfeeding. Results of the literature search reported here (finalized on 17 April 2020) revealed a single study providing some evidence of vertical transmission of human coronavirus 229E; a single study evaluating presence of SARS-CoV in human milk (it was negative); and no published data on MERS-CoV and human milk. We identified 13 studies reporting human milk tested for SARS-CoV-2; one study (a non-peer-reviewed preprint) detected the virus in one milk sample, and another study detected SARS-CoV-2 specific IgG in milk. Importantly, none of the studies on coronaviruses and human milk report validation of their collection and analytical methods for use in human milk. These reports are evaluated here, and their implications related to the possibility of vertical transmission of coronaviruses (in particular, SARS-CoV-2) during breastfeeding are discussed.
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COVID-19/transmissão , COVID-19/virologia , Transmissão Vertical de Doenças Infecciosas/estatística & dados numéricos , Leite Humano/virologia , SARS-CoV-2/isolamento & purificação , Adulto , Anticorpos Antivirais/análise , Aleitamento Materno , COVID-19/diagnóstico , Teste para COVID-19 , Feminino , Idade Gestacional , Humanos , Imunoglobulina G/análise , Lactente , Recém-Nascido , Masculino , Gravidez , Complicações Infecciosas na Gravidez/virologia , SARS-CoV-2/imunologiaRESUMO
BACKGROUND: Numerous reports have documented bacteria in the placental membranes and basal plate decidua in the absence of immunopathology using histologic techniques. Similarly, independent metagenomic characterizations have identified an altered taxonomic makeup in association with spontaneous preterm birth. Here we sought to corroborate these findings by localizing presumptive intact bacteria using molecular histology within the placental microanatomy. OBJECTIVE: Here we examined for microbes in term and preterm gestations using a signal-amplified 16S universal in situ hybridization probe set for bacterial rRNA, alongside traditional histologic methods of Warthin-Starry and Gram stains, as well as clinical culture methodologies. We further sought to differentiate accompanying 16S gene sequencing taxonomic profiles from germ-free (gnotobiotic) mouse and extraction and amplicon contamination controls. STUDY DESIGN: Placentas were collected from a total of 53 subjects, composed of term labored (n = 4) and unlabored cesarean deliveries (n = 22) and preterm vaginal (n = 18) and cesarean deliveries (n = 8); a placenta from a single subject with clinical and histologic evident choriomanionitis was employed as a positive control (n = 1). The preterm cohort included spontaneous preterm birth with (n = 6) and without (n = 10) preterm premature rupture of membranes, as well as medically indicated preterm births (n = 10). Placental microbes were visualized using an in situ hybridization probe set designed against highly conserved regions of the bacterial 16S ribosome, which produces an amplified stable signal using branched DNA probes. Extracted bacterial nucleic acids from these same samples were subjected to 16S rRNA metagenomic sequencing (Illumina, V4) for course taxonomic analysis, alongside environmental and kit contaminant controls. A subset of unlabored, cesarean-delivered term pregnancies were also assessed with clinical culture for readily cultivatable pathogenic microbes. RESULTS: Molecular in situ hybridization of bacterial rRNA enabled visualization and localization of low-abundance microbes after systematic high-power scanning. Despite the absence of clinical or histologic chorioamnionitis in 52 of 53 subjects, instances of 16S rRNA signal were confidently observed in 13 of 16 spontaneous preterm birth placentas, which was not significantly different from term unlabored cesarean specimens (18 of 22; P > .05). 16S rRNA signal was largely localized to the villous parenchyma and/or syncytiotrophoblast, and less commonly the chorion and the maternal intervillous space. In all term and unlabored cesarean deliveries, visualization of evident placental microbes by in situ hybridization occurred in the absence of clinical or histologic detection using conventional clinical cultivation, hematoxylin-eosin, and Gram staining. In 1 subject, appreciable villous bacteria localized to an infarction, where 16S microbial detection was confirmed by Warthin-Starry stain. In all instances, parallel sample principle coordinate analysis using Bray-Cutis distances of 16S rRNA gene sequencing data demonstrated consistent taxonomic distinction from all negative or potential contamination controls (P = .024, PERMANOVA). Classification from contaminant filtered data identified a distinct taxonomic makeup among term and preterm cohorts when compared with contaminant controls (false discovery rate <0.05). CONCLUSION: Presumptively intact placental microbes are visualized as low-abundance, low-biomass and sparse populations within the placenta regardless of gestational age and mode of delivery. Their taxonomic makeup is distinct from contamination controls. These findings further support several previously published findings, including our own, which have used metagenomics to characterize low-abundance and low-biomass microbial communities in the placenta.
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Placenta/microbiologia , RNA Ribossômico 16S , Adulto , Código de Barras de DNA Taxonômico , Feminino , Humanos , Hibridização In Situ , Metagenômica , Microbiota , Gravidez , Nascimento Prematuro , RNA Bacteriano/análise , Análise de Sequência de RNA , Nascimento a TermoRESUMO
Previously we have shown that the Japanese macaque gut microbiome differs not by obesity per se, but rather in association with high-fat diet (HFD) feeding. This held true for both pregnant dams, as well as their 1-year-old offspring, even when weaned onto a control diet. Here we aimed to examine the stability of the gut microbiome over time and in response to maternal and postweaning HFD feeding from 6 months of age, and at 1 and 3 years of age. In both cross-sectional and longitudinal specimens, we performed analysis of the V4 hypervariable region of the 16S rRNA gene on anus swabs collected from pregnant dams and their juveniles at age 6 months to 3 years (n = 55). Extracted microbial DNA was subjected to 16S-amplicon-based metagenomic sequencing on the Illumina MiSeq platform. We initially identified 272 unique bacterial genera, and multidimensional scaling revealed samples to cluster by age and diet exposures. Dirichlet multinomial mixture modeling of microbiota abundances enabled identification of two predominant enterotypes to which samples sorted, characterized primarily by Treponema abundance, or lack thereof. Approximating the time of initial weaning (6 months), the Japanese macaque offspring microbiome underwent a significant state type transition which stabilized from 1 to 3 years of age. However, we also found the low abundance Treponema enterotype to be strongly associated with HFD exposure, be it during gestation/lactation or in the postweaning interval. Examination of taxonomic co-occurrences revealed samples within the low Treponema cluster were relatively permissive (allowing for increased interactions between microbiota) whereas samples within the high Treponema cluster were relatively exclusionary (suggesting decreased interactions amongst microbiota). Taken together, these findings suggest that Treponemes are keystone species in the developing gut microbiome of the gut, and susceptible to HFD feeding in their relative abundance.
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Dieta/veterinária , Microbioma Gastrointestinal , Macaca fuscata/microbiologia , Fatores Etários , Animais , Bactérias/classificação , Dieta Hiperlipídica/veterinária , Feminino , Genoma Bacteriano , Estudos Longitudinais , Macaca fuscata/crescimento & desenvolvimento , Gravidez , RNA Ribossômico 16S/genética , Treponema , DesmameRESUMO
BACKGROUND: We and others have previously shown that alterations in the mammalian gut microbiome are associated with diet, notably early life exposure to a maternal high fat diet (HFD). Here, we aimed to further these studies by examining alterations in the gut microbiome of juvenile Japanese macaques (Macaca fuscata) that were exposed to a maternal HFD, weaned onto a control diet, and later supplemented with a synbiotic comprised of psyllium seed and Enterococcus and Lactobacillus species. RESULTS: Eighteen month old offspring (n = 7) of 36% HFD fed dams were fed a control (14% fat) diet post weaning, then were synbiotic supplemented for 75 days and longitudinal stool and serum samples were obtained. All stool samples were subjected to 16S rRNA metagenomic sequencing, and microbiome profiles and serum lipids and triglycerides were compared to untreated, healthy age matched and diet matched controls (n = 7). Overall, 16S-based metagenomic analysis revealed that supplementation exerted minimal alterations to the gut microbiome including transient increased abundance of Lactobacillus species and decreased abundance of few bacterial genera, including Faecalibacterium and Anaerovibrio. However, serum lipid analysis revealed significant decreases in triglycerides, cholesterol, and LDL (p < 0.05). Nevertheless, supplemented juveniles challenged 4 months later were not protected from HFD-induced gut dysbiosis. CONCLUSIONS: Synbiotic supplementation is temporally associated with alterations in the gut microbiome and host lipid profiles of juvenile Japanese macaques that were previously exposed to a maternal HFD. Despite these presumptive temporal benefits, a protective effect against later HFD-challenge gut dysbiosis was not observed.
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Bactérias/classificação , Bactérias/metabolismo , Dieta Hiperlipídica , Microbioma Gastrointestinal/fisiologia , Primatas/microbiologia , Simbióticos , Animais , Bactérias/genética , Disbiose/microbiologia , Enterococcus/fisiologia , Faecalibacterium , Fezes/microbiologia , Feminino , Firmicutes , Microbioma Gastrointestinal/genética , Lactobacillus/fisiologia , Lipídeos/sangue , Macaca/microbiologia , Masculino , Redes e Vias Metabólicas , Metagenômica , Probióticos , Psyllium , RNA Ribossômico 16S/genética , Especificidade da Espécie , Triglicerídeos/sangueRESUMO
The spider mite Tetranychus urticae is a cosmopolitan agricultural pest with an extensive host plant range and an extreme record of pesticide resistance. Here we present the completely sequenced and annotated spider mite genome, representing the first complete chelicerate genome. At 90 megabases T. urticae has the smallest sequenced arthropod genome. Compared with other arthropods, the spider mite genome shows unique changes in the hormonal environment and organization of the Hox complex, and also reveals evolutionary innovation of silk production. We find strong signatures of polyphagy and detoxification in gene families associated with feeding on different hosts and in new gene families acquired by lateral gene transfer. Deep transcriptome analysis of mites feeding on different plants shows how this pest responds to a changing host environment. The T. urticae genome thus offers new insights into arthropod evolution and plant-herbivore interactions, and provides unique opportunities for developing novel plant protection strategies.
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Adaptação Fisiológica/genética , Genoma/genética , Herbivoria/genética , Tetranychidae/genética , Tetranychidae/fisiologia , Adaptação Fisiológica/fisiologia , Animais , Ecdisterona/análogos & derivados , Ecdisterona/genética , Evolução Molecular , Fibroínas/genética , Regulação da Expressão Gênica , Transferência Genética Horizontal/genética , Genes Homeobox/genética , Genômica , Herbivoria/fisiologia , Dados de Sequência Molecular , Muda/genética , Família Multigênica/genética , Nanoestruturas/química , Plantas/parasitologia , Seda/biossíntese , Seda/química , Transcriptoma/genéticaRESUMO
Wnt genes are a family of conserved glycoprotein ligands that play a role in a wide variety of cell and developmental processes, from cell proliferation to axis elongation. There are 13 Wnt subfamilies found among metazoans. Eleven of these appear conserved in arthropods with a pattern of loss during evolution of as many as six subfamilies among hexapods. Here we report on Wnt genes in the branchiopod crustacean, Thamnocephalus platyurus, including the first documentation of the expression of the complete Wnt gene family in a crustacean. Our results suggest fewer Wnt genes were retained in Thamnocephalus than in the related crustacean, Daphnia, although the Thamnocephalus Wnt repertoire is larger than that found in insects. We also find an intriguing pattern of staggered expression of Wnts-an anterior-posterior stagger within the posterior growth zone and a dorsal-ventral stagger in the developing segments-suggesting a potential for subfunctionalization of Wnts in these regions.
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Anostraca/genética , Proteínas de Artrópodes/genética , Regulação da Expressão Gênica no Desenvolvimento , Proteínas Wnt/genética , Animais , Anostraca/embriologia , Proteínas de Artrópodes/metabolismo , Clonagem Molecular , DNA Complementar/genética , DNA Complementar/metabolismo , Evolução Molecular , Filogenia , Análise de Sequência de DNA , Proteínas Wnt/metabolismoRESUMO
Metazoans are known to contain a limited, yet highly conserved, set of signal transduction pathways that instruct early developmental patterning mechanisms. Genomic surveys that have compared gene conservation in signal transduction pathways between various insects and Drosophila support the conclusion that these pathways are conserved in evolution. However, the degree to which individual components of signal transduction pathways vary among more divergent arthropods is not known. Here, we report our results of a survey of the genome of the two-spotted spider mite Tetranychus urticae, using a set of 294 Drosophila orthologs of genes that function in signal transduction. We find a third of all genes surveyed absent from the spider mite genome. We also identify several novel duplications that have not been previously reported for a chelicerate. In comparison with previous insect surveys, Tetranychus contains a decrease in overall gene conservation, as well as an unusual ratio of ligands to receptors and other modifiers. These findings suggest that gene loss and duplication among components of signal transduction pathways are common among arthropods and suggest that signal transduction pathways in arthropods are more evolutionarily labile than previously hypothesized.
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Artrópodes/genética , Artrópodes/metabolismo , Transdução de Sinais , Animais , Artrópodes/classificação , Drosophila/genética , Drosophila/metabolismo , Genoma , Filogenia , Tetranychidae/genética , Tetranychidae/metabolismoRESUMO
Background: There is a paucity of data on the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in feces of lactating women with coronavirus disease 2019 (COVID-19) and their breastfed infants as well as associations between fecal shedding and symptomatology. Objective: We examined whether and to what extent SARS-CoV-2 is detectable in the feces of lactating women and their breastfed infants following maternal COVID-19 diagnosis. Methods: This was a longitudinal study carried out from April 2020 to December 2021 involving 57 breastfeeding maternal-infant dyads: 33 dyads were enrolled within 7 d of maternal COVID-19 diagnosis, and 24 healthy dyads served as controls. Maternal/infant fecal samples were collected by participants, and surveys were administered via telephone over an 8-wk period. Feces were analyzed for SARS-CoV-2 RNA. Results: Signs/symptoms related to ears, eyes, nose, and throat (EENT); general fatigue/malaise; and cardiopulmonary signs/symptoms were commonly reported among mothers with COVID-19. In infants of mothers with COVID-19, EENT, immunologic, and cardiopulmonary signs/symptoms were most common, but prevalence did not differ from that of infants of control mothers. SARS-CoV-2 RNA was detected in feces of 7 (25%) women with COVID-19 and 10 (30%) of their infants. Duration of fecal shedding ranged from 1-4 wk for both mothers and infants. SARS-CoV-2 RNA was sparsely detected in feces of healthy dyads, with only one mother's and two infants' fecal samples testing positive. There was no relationship between frequencies of maternal and infant SARS-CoV-2 fecal shedding (P=0.36), although presence of maternal or infant fever was related to increased likelihood (7-9 times greater, P≤0.04) of fecal shedding in infants of mothers with COVID-19.
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COVID-19 , Lactente , Humanos , Feminino , Masculino , COVID-19/diagnóstico , COVID-19/epidemiologia , SARS-CoV-2 , Aleitamento Materno , Teste para COVID-19 , Lactação , Estudos Longitudinais , RNA Viral , Prevalência , FezesRESUMO
The human milk microbiome (HMM) is hypothesized to be seeded by multiple factors, including the infant oral microbiome during breastfeeding. However, it is not known whether breastfeeding patterns (e.g., frequency or total time) impact the composition of the HMM. As part of the Mother-Infant Microbiomes, Behavior, and Ecology Study (MIMBES), we analyzed data from naturalistic observations of 46 mother-infant dyads living in the US Pacific Northwest and analyzed milk produced by the mothers for its bacterial diversity and composition. DNA was extracted from milk and the V1-V3 region of the 16S rRNA gene was amplified and sequenced. We hypothesized that number of breastfeeding bouts (breastfeeding sessions separated by >30 seconds) and total time breastfeeding would be associated with HMM α-diversity (richness, diversity, or evenness) and differential abundance of HMM bacterial genera. Multiple linear regression was used to examine associations between HMM α-diversity and the number of breastfeeding bouts or total time breastfeeding and selected covariates (infant age, maternal work outside the home, frequency of allomother physical contact with the infant, non-household caregiving network). HMM richness was inversely associated with number of breastfeeding bouts and frequency of allomother physical contact, but not total time breastfeeding. Infants' non-household caregiving network was positively associated with HMM evenness. In two ANCOM-BC analyses, abundances of 5 of the 35 most abundant genera were differentially associated with frequency of breastfeeding bouts (Bifidobacterium, Micrococcus, Pedobacter, Acidocella, Achromobacter); 5 genera (Bifidobacterium, Agreia, Pedobacter, Rugamonas, Stenotrophomonas) were associated with total time breastfeeding. These results indicate that breastfeeding patterns and infant caregiving ecology may play a role in influencing HMM composition. Future research is needed to identify whether these relationships are consistent in other populations and if they are associated with variation in the infant's gastrointestinal (including oral) microbiome.
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Microbiota , Leite Humano , Feminino , Humanos , Lactente , Leite Humano/microbiologia , Aleitamento Materno , Mães , RNA Ribossômico 16S/genética , Microbiota/genética , Bactérias/genéticaRESUMO
There is growing interest in a functional understanding of milk-associated microbiota as there is ample evidence that host-associated microbial communities play an active role in host health and phenotype. Mastitis, characterized by painful inflammation of the mammary gland, is prevalent among lactating humans and agricultural animals and is associated with significant clinical and economic consequences. The etiology of mastitis is complex and polymicrobial and correlative studies have indicated alterations in milk microbial community composition. Recent evidence is beginning to suggest that a causal relationship may exist between the milk microbiota and host phenotype in mastitis. Multi-omic approaches can be leveraged to gain a mechanistic, molecular level understanding of how the milk microbiome might modulate host physiology, thereby informing strategies to prevent and ameliorate mastitis. In this paper, we review existing studies that have utilized omics approaches to investigate the role of the milk microbiome in mastitis. We also summarize the strengths and challenges associated with the different omics techniques including metagenomics, metatranscriptomics, metaproteomics, metabolomics and lipidomics and provide perspective on the integration of multiple omics technologies for a better functional understanding of the milk microbiome.
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The sodium (Na) concentration and the ratio of Na to potassium (K; Na/K) in human milk are used commonly as biomarkers of subclinical mastitis, but limited data exist on their relationship to and ability to predict clinical mastitis. Here, we assessed concentrations of Na, K, Na/K, and somatic cell count (SCC), a mammary health biomarker used in the dairy industry, in milk prospectively collected from both breasts of 41 women over the first 6 weeks postpartum. Although values differed over time postpartum, there were no differences in mean values between breasts. Nearly one-quarter (24%) of participants experienced clinical mastitis. Somatic cell counts >4.76 × 105 cells/mL were most strongly related to development of clinical mastitis in the following week (odds ratio, 7.81; 95% CI, 2.15−28.30; p = 0.002), although relationships were also observed for SCC > 4.00 × 105 cells/mL and Na concentration >12 mmol/L. Estimates of the prevalence of subclinical mastitis in women who never progressed to clinical mastitis differed by biomarker but ranged from 20 to 75%. Despite these findings, positive predictive values (PPV) of the biomarkers for identifying clinical mastitis were low (≤0.34), indicating additional research is needed to identify single biomarkers or composite measures that are highly specific, sensitive, and predictive of clinical mastitis in women.
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Mastite , Leite Humano , Humanos , Feminino , Leite Humano/química , Potássio/análise , Sódio/análise , Mastite/diagnóstico , Mastite/epidemiologia , Contagem de Células , Período Pós-Parto , Íons , BiomarcadoresRESUMO
Infants exposed to caregivers infected with SARS-CoV-2 may have heightened infection risks relative to older children due to their more intensive care and feeding needs. However, there has been limited research on COVID-19 outcomes in exposed infants beyond the neonatal period. Between June 2020 - March 2021, we conducted interviews and collected capillary dried blood spots from 46 SARS-CoV-2 infected mothers and their infants (aged 1-36 months) for up to two months following maternal infection onset (COVID+ group, 87% breastfeeding). Comparative data were also collected from 26 breastfeeding mothers with no known SARS-CoV-2 infection or exposures (breastfeeding control group), and 11 mothers who tested SARS-CoV-2 negative after experiencing symptoms or close contact exposure (COVID- group, 73% breastfeeding). Dried blood spots were assayed for anti-SARS-CoV-2 S-RBD IgG and IgA positivity and anti-SARS-CoV-2 S1 + S2 IgG concentrations. Within the COVID+ group, the mean probability of seropositivity among infant samples was lower than that of corresponding maternal samples (0.54 and 0.87, respectively, for IgG; 0.33 and 0.85, respectively, for IgA), with likelihood of infant infection positively associated with the number of maternal symptoms and other household infections reported. COVID+ mothers reported a lower incidence of COVID-19 symptoms among their infants as compared to themselves and other household adults, and infants had similar PCR positivity rates as other household children. No samples returned by COVID- mothers or their infants tested antibody positive. Among the breastfeeding control group, 44% of mothers but none of their infants tested antibody positive in at least one sample. Results support previous research demonstrating minimal risks to infants following maternal COVID-19 infection, including for breastfeeding infants.
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COVID-19 , SARS-CoV-2 , Lactente , Recém-Nascido , Adulto , Feminino , Criança , Humanos , Adolescente , Anticorpos Antivirais , Imunoglobulina G , Imunoglobulina ARESUMO
BACKGROUND: Lactobacillus was described as a keystone bacterial taxon in the human vagina over 100 years ago. Using metagenomics, we and others have characterized lactobacilli and other vaginal taxa across health and disease states, including pregnancy. While shifts in community membership have been resolved at the genus/species level, strain dynamics remain poorly characterized. METHODS: We performed a metagenomic analysis of the complex ecology of the vaginal econiche during and after pregnancy in a large U.S. based longitudinal cohort of women who were initially sampled in the third trimester of pregnancy, then validated key findings in a second cohort of women initially sampled in the second trimester of pregnancy. FINDINGS: First, we resolved microbial species and strains, interrogated their co-occurrence patterns, and probed the relationship between keystone species and preterm birth outcomes. Second, to determine the role of human heredity in shaping vaginal microbial ecology in relation to preterm birth, we performed a mtDNA-bacterial species association analysis. Finally, we explored the clinical utility of metagenomics in detection and co-occurrence patterns for the pathobiont Group B Streptococcus (causative bacterium of invasive neonatal sepsis). CONCLUSIONS: Our highly refined resolutions of the vaginal ecology during and post-pregnancy provide insights into not only structural and functional community dynamics, but highlight the capacity of metagenomics to reveal finer aspects of the vaginal microbial ecologic framework. FUNDING: NIH-NINR R01NR014792, NIH-NICHD R01HD091731, NIH National Children's Study Formative Research, Burroughs Wellcome Fund Preterm Birth Initiative, March of Dimes Preterm Birth Research Initiative, NIH-NIGMS (K12GM084897, T32GM007330, T32GM088129).
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Microbiota , Nascimento Prematuro , Bactérias , Criança , Feminino , Humanos , Recém-Nascido , Lactobacillus/genética , Microbiota/genética , Período Pós-Parto , Gravidez , Nascimento Prematuro/microbiologia , RNA Ribossômico 16S/genética , Vagina/químicaRESUMO
In addition to providing life-giving nutrients and other substances to the breastfed infant, human milk can also represent a vehicle of pathogen transfer. As such, when an infectious disease outbreak, epidemic, or pandemic occurs-particularly when it is associated with a novel pathogen-the question will naturally arise as to whether the pathogen can be transmitted through breastfeeding. Until high-quality data are generated to answer this question, abandonment of breastfeeding due to uncertainty can result. The COVID-19 pandemic, which was in full swing at the time this document was written, is an excellent example of this scenario. During these times of uncertainty, it is critical for investigators conducting research to assess the possible transmission of pathogens through milk, whether by transfer through the mammary gland or contamination from respiratory droplets, skin, breast pumps, and milk containers, and/or close contact between mother and infant. To promote the most rigorous science, it is critical to outline optimal methods for milk collection, handling, storage, and analysis in these situations, and investigators should openly share their methods in published materials. Otherwise, the risks of inconsistent test results from preanalytical and analytical variation, false positives, and false negatives are unacceptably high and the ability to provide public health guidance poor. In this study, we provide "best practices" for collecting human milk samples for COVID-19 research with the intention that this will also be a useful guide for future pandemics.
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Benchmarking , Aleitamento Materno/métodos , COVID-19/prevenção & controle , Controle de Infecções/métodos , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , COVID-19/transmissão , Feminino , Humanos , Recém-Nascido , Intenção , Leite Humano/virologia , Mães/psicologia , SARS-CoV-2RESUMO
Whether mother-to-infant SARS-CoV-2 transmission can occur during breastfeeding and, if so, whether the benefits of breastfeeding outweigh this risk during maternal COVID-19 illness remain important questions. Using RT-qPCR, we did not detect SARS-CoV-2 RNA in any milk sample (n = 37) collected from 18 women following COVID-19 diagnosis. Although we detected evidence of viral RNA on 8 out of 70 breast skin swabs, only one was considered a conclusive positive result. In contrast, 76% of the milk samples collected from women with COVID-19 contained SARS-CoV-2-specific IgA, and 80% had SARS-CoV-2-specific IgG. In addition, 62% of the milk samples were able to neutralize SARS-CoV-2 infectivity in vitro, whereas milk samples collected prior to the COVID-19 pandemic were unable to do so. Taken together, our data do not support mother-to-infant transmission of SARS-CoV-2 via milk. Importantly, milk produced by infected mothers is a beneficial source of anti-SARS-CoV-2 IgA and IgG and neutralizes SARS-CoV-2 activity. These results support recommendations to continue breastfeeding during mild-to-moderate maternal COVID-19 illness.IMPORTANCE Results from prior studies assaying human milk for the presence of SARS-CoV-2, the causative virus of COVID-19, have suggested milk may act as a potential vehicle for mother-to-child transmission. Most previous studies are limited because they followed only a few participants, were cross-sectional, and/or failed to report how milk was collected and/or analyzed. As such, considerable uncertainty remains regarding whether human milk is capable of transmitting SARS-CoV-2 from mother to child. Here, we report that repeated milk samples collected from 18 women following COVID-19 diagnosis did not contain SARS-CoV-2 RNA; however, risk of transmission via breast skin should be further evaluated. Importantly, we found that milk produced by infected mothers is a source of anti-SARS-CoV-2 IgA and IgG and neutralizes SARS-CoV-2 activity. These results support recommendations to continue breastfeeding during mild-to-moderate maternal COVID-19 illness as milk likely provides specific immunologic benefits to infants.
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Anticorpos Neutralizantes/metabolismo , Anticorpos Antivirais/metabolismo , COVID-19/imunologia , Leite Humano/imunologia , Complicações Infecciosas na Gravidez/imunologia , SARS-CoV-2/imunologia , Adulto , Mama/virologia , Aleitamento Materno , COVID-19/transmissão , COVID-19/virologia , Feminino , Humanos , Lactente , Transmissão Vertical de Doenças Infecciosas , Masculino , Leite Humano/virologia , Mães , Gravidez , Complicações Infecciosas na Gravidez/virologia , RNA Viral/isolamento & purificação , SARS-CoV-2/isolamento & purificaçãoRESUMO
Previously published data from our group and others demonstrate that human milk oligosaccharide (HMOs), as well as milk and infant fecal microbial profiles, vary by geography. However, little is known about the geographical variation of other milk-borne factors, such as lactose and protein, as well as the associations among these factors and microbial community structures in milk and infant feces. Here, we characterized and contrasted concentrations of milk-borne lactose, protein, and HMOs, and examined their associations with milk and infant fecal microbiomes in samples collected in 11 geographically diverse sites. Although geographical site was strongly associated with milk and infant fecal microbiomes, both sample types assorted into a smaller number of community state types based on shared microbial profiles. Similar to HMOs, concentrations of lactose and protein also varied by geography. Concentrations of HMOs, lactose, and protein were associated with differences in the microbial community structures of milk and infant feces and in the abundance of specific taxa. Taken together, these data suggest that the composition of human milk, even when produced by relatively healthy women, differs based on geographical boundaries and that concentrations of HMOs, lactose, and protein in milk are related to variation in milk and infant fecal microbial communities.
RESUMO
Background: Limited data are available regarding the balance of risks and benefits from human milk and/or breastfeeding during and following maternal infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Objective: To investigate whether SARS-CoV-2 can be detected in milk and on the breast after maternal coronavirus disease 2019 (COVID-19) diagnosis; and characterize concentrations of milk immunoglobulin (Ig) A specific to the SARS-CoV-2 spike glycoprotein receptor binding domain (RBD) during the 2 months after onset of symptoms or positive diagnostic test. Methods: Using a longitudinal study design, we collected milk and breast skin swabs one to seven times from 64 lactating women with COVID-19 over a 2-month period, beginning as early as the week of diagnosis. Milk and breast swabs were analyzed for SARS-CoV-2 RNA, and milk was tested for anti-RBD IgA. Results: SARS-CoV-2 was not detected in any milk sample or on 71% of breast swabs. Twenty-seven out of 29 (93%) breast swabs collected after breast washing tested negative for SARS-CoV-2. Detection of SARS-CoV-2 on the breast was associated with maternal coughing and other household COVID-19. Most (75%; 95% CI, 70-79%; n=316) milk samples contained anti-RBD IgA, and concentrations increased (P=.02) during the first two weeks following onset of COVID-19 symptoms or positive test. Milk-borne anti-RBD IgA persisted for at least two months in 77% of women. Conclusion: Milk produced by women with COVID-19 does not contain SARS-CoV-2 and is likely a lasting source of passive immunity via anti-RBD IgA. These results support recommendations encouraging lactating women to continue breastfeeding during and after COVID-19 illness.
Assuntos
Anticorpos Antivirais/análise , Imunoglobulina A/análise , Leite Humano/imunologia , SARS-CoV-2/imunologia , Adulto , Anticorpos Antivirais/imunologia , Aleitamento Materno , COVID-19/imunologia , Feminino , Humanos , Imunização Passiva , Imunoglobulina A/imunologia , Lactação , Estudos Longitudinais , Leite Humano/virologia , RNA Viral/genéticaRESUMO
Human milk is the optimal nutrition source for infants, and oligosaccharides represent the third most abundant component in milk after lactose and fat. Human milk oligosaccharides (HMO) are favorable macromolecules which are, interestingly, indigestible by the infant but serve as substrates for bacteria. Hypothesizing that the maternal diet itself might influence HMO composition, we sought to directly determine the effect maternal diet on HMO and the milk bacteria. Employing a human cross-over study design, we demonstrate that distinct maternal dietary carbohydrate and energy sources preferentially alter milk concentrations of HMO, including fucosylated species. We find significant associations between the concentration of HMO-bound fucose and the abundance of fucosidase (a bacterial gene that digests fucose moieties) harbored by milk bacteria. These studies reveal a successive mechanism by which the maternal diet during lactation alters milk HMO composition, which in turn shapes the functional milk microbiome prior to infant ingestion.