RESUMEN
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 , Nacimiento Prematuro , Bacterias , Niño , Femenino , Humanos , Recién Nacido , Lactobacillus/genética , Microbiota/genética , Periodo Posparto , Embarazo , Nacimiento Prematuro/microbiología , ARN Ribosómico 16S/genética , Vagina/químicaRESUMEN
BACKGROUND: Reliable prediction of spontaneous preterm birth remains limited, particularly for nulliparous and multiparous women without a personal history of preterm birth. Although previous preterm birth is a risk factor for recurrent preterm birth, most spontaneous preterm births occur in women with no previous history of preterm birth. OBJECTIVE: This study aimed to determine whether patients' self-reported maternal family history of preterm births among siblings and across 3 generations was an independent risk factor for spontaneous preterm births after controlling for potential confounders. STUDY DESIGN: This was a retrospective analysis of a prospectively acquired cohort using a comprehensive single, academic center database of deliveries from August 2011 to July 2017. The objective of the current analysis was to evaluate the risk of preterm birth among women with and without a family history of preterm birth. All subjects in the database were directly queried regarding familial history across 3 generations, inclusive of obstetrical morbidities. Index subjects with probable indicated preterm birth (eg, concurrent diagnosis of preeclampsia; hemolysis, elevated liver enzymes, and low platelet count; or placenta previa or placenta accreta) were excluded, as were nonsingleton pregnancies. Univariate and multivariate analyses with logistic regression were used to determine significance and adjusted relative risk. RESULTS: In this study, 23,816 deliveries were included, with 2345 (9.9%) born prematurely (<37 weeks' gestation). Across all subjects, preterm birth was significantly associated with a maternal family history of preterm birth by any definition (adjusted relative risk, 1.44; P<.001), and the fraction of preterm birth occurring in women with a positive family history increased with decreasing gestational age at which the index subjects of preterm birth occurred. For nulliparous women, a history in the subject's sister posed the greatest risk (adjusted relative risk, 2.25; P=.003), whereas for multiparous women with no previous preterm birth, overall family history was most informative (P=.003). Interestingly, a personal history of the index subject herself being born preterm presented the greatest individual risk factor (adjusted relative risk, 1.94; P=.004). CONCLUSION: Spontaneous preterm birth in the current pregnancy was significantly associated with a maternal family history of preterm birth among female relatives within 3 generations and notably sisters. The risk persisted among gravidae without a previous preterm birth, demonstrating the capacity for familial history to independently predict risk of spontaneous preterm birth even in the context of a negative personal history. This study provides evidence that self-reported maternal family history is relevant in a US population cohort and across more distant generations than has previously been reported.
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Preeclampsia , Nacimiento Prematuro , Femenino , Edad Gestacional , Humanos , Recién Nacido , Embarazo , Nacimiento Prematuro/epidemiología , Estudios Retrospectivos , Factores de RiesgoRESUMEN
OBJECTIVE: To evaluate the association between Hurricane Harvey landfall with maternal and neonatal morbidity. METHODS: Using an institutional perinatal database from two hospitals in Houston, Texas, women with nonanomalous singletons delivering after 24 weeks of gestation between August 2011 and June 2018 were included. To evaluate the possible association of hurricane landfall with pregnancy outcomes, gravid women delivering within 280 days (40 weeks of gestation) on or after August 25, 2017 (the day of hurricane landfall) were categorized as exposed, and women who delivered before August 25, 2017, were the reference group. Composite maternal morbidity included any of the following: hypertensive disorders of pregnancy, chorioamnionitis, endometritis, blood transfusion, peripartum hysterectomy, maternal critical care admission, pulmonary edema, or maternal death. Composite neonatal morbidity included any of the following: 5-minute Apgar score 3 or less, respiratory distress syndrome, use of ventilator or continuous positive airway pressure, suspected newborn sepsis, seizure, stillbirth, or neonatal death. Adjusted odds ratios (aORs) were calculated after correcting for possible confounders identified on univariate analysis. Disruption in outcome trends were measured in time series analyses. RESULTS: Of 40,502 deliveries in our database, 29,179 (72%) met the inclusion criteria, with 3,842 (13.2%) delivering within 280 days of Hurricane Harvey landfall. Women delivering after Hurricane Harvey were on average less likely to be obese and more likely to be older, Caucasian, married, have a household income higher than $75,000, a high school education, and private insurance. However, compared with the cohort of gravid patients who delivered before Hurricane Harvey, composite maternal morbidity increased by 27% (11.5% vs 14.7%, aOR 1.27, 95% CI 1.14-1.42) after the storm. Composite neonatal morbidity increased by 50% (7.8% vs 11.9%, aOR 1.52, 95% CI 1.34-1.71). In time series analyses, we observed a significant shift in composite maternal morbidity specific to women of low socioeconomic status (estimate 2.87, P=.028). CONCLUSION: Despite having fewer at-risk baseline characteristics, gravid patients delivering after landfall by Hurricane Harvey had a significantly higher likelihood of adverse outcomes as did their neonates.
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Tormentas Ciclónicas , Enfermedades del Recién Nacido , Complicaciones del Embarazo , Resultado del Embarazo/epidemiología , Adulto , Bases de Datos Factuales/estadística & datos numéricos , Femenino , Edad Gestacional , Humanos , Lactante , Mortalidad Infantil , Recién Nacido , Enfermedades del Recién Nacido/clasificación , Enfermedades del Recién Nacido/epidemiología , Masculino , Mortalidad Materna , Desastres Naturales , Embarazo , Complicaciones del Embarazo/clasificación , Complicaciones del Embarazo/epidemiología , Factores de Riesgo , Texas/epidemiologíaRESUMEN
The human body is cohabitated with trillions of commensal bacteria that are essential for our health. However, certain bacteria can also cause diseases in the human host. Before the microbiome can be attributed to disease risk and pathogenesis, normal acquisition and development of the microbiome must be understood. Here, we explore the evidence surrounding in utero microbial exposures and the significant of this exposure in the proper development of the fetal and neonatal microbiome. We further explore the development of the fetal and neonatal microbiome and its relationship to preterm birth, feeding practices, and mode of delivery, and maternal diet.
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Feto/microbiología , Microbiota , Femenino , Humanos , Recién Nacido , Fenómenos Fisiologicos Nutricionales Maternos , Embarazo , Útero/microbiologíaRESUMEN
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/microbiología , ARN Ribosómico 16S , Adulto , Código de Barras del ADN Taxonómico , Femenino , Humanos , Hibridación in Situ , Metagenómica , Microbiota , Embarazo , Nacimiento Prematuro , ARN Bacteriano/análisis , Análisis de Secuencia de ARN , Nacimiento a TérminoRESUMEN
OBJECTIVE: To assess whether recent anti-immigration rhetoric is significantly associated with inadequate prenatal care. METHODS: This was a population-based cohort study (2011-2017). In their native language, patients were consented and queried regarding country of origin and time in the United States. Additional variables were collected or abstracted from the medical record, including documentation and timing of prenatal visits. Based on relevance and prevalence during the study period, publicly available Google search trends were mined for the terms "Make America Great Again," "Mexico Wall," and "Deportation" by geographic region. The time of first deviation from the mode Google search popularity value for each term was ascertained (mode inflection date). Perinatal data was averaged over 15 days moving windows, and the Adequacy of Prenatal Care Utilization Index was used to categorically define inadequate prenatal care by validated standards. RESULTS: Twenty-four thousand nine hundred thirty-three deliveries occurred during the study period. A mode inflection date was extrapolated from Google trend analytics and used to define the period before change in trends use pre (before rhetoric) and post (after rhetoric). Coincident to the rhetoric change, there was a significant increase in days until the first prenatal visit, fewer prenatal visits, and a decreased trend of mean hemoglobin nadir among U.S. non-native Hispanic women (P<.001). Immigrant status was an independent predictor of inadequate prenatal care as defined by the Adequacy of Prenatal Care Utilization Index standard, with increased adjusted odds among Hispanic women (adjusted odds ratio 1.581, 95% CI 1.407-1.777 [1.4-1.8]) coincident with anti-immigration rhetoric. CONCLUSION: Our findings are of likely significant public health importance and suggest that recent anti-immigrant rhetoric is associated with adequate, timely, and regular access to prenatal care among nearly 25,000 deliveries in Houston, Texas.
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Parto Obstétrico/estadística & datos numéricos , Emigrantes e Inmigrantes , Accesibilidad a los Servicios de Salud , Atención Prenatal , Adulto , América Central/etnología , Estudios de Cohortes , Femenino , Humanos , México/etnología , Política , Embarazo , América del Sur/etnología , Texas , Servicios de Salud para MujeresRESUMEN
The microbiome is thought to play a role in the maintenance of a healthy pregnancy and thus may either contribute to or protect from preterm birth. Study of the human microbiome has been aided by metagenomic sequencing approaches, providing greater insight into the commensal bacteria that coexist in and on our bodies. The vaginal microbiome has been the most widely studied, though there have been recent efforts to explore the gut, cervical-vaginal, placental and oral microbiomes in the further search of etiologies of preterm birth. To date, a specific microbiome community or microorganism has yet to be reliably associated with preterm birth. This is partly due to the fact that the 'normal' constituents' microbiome can vary widely between healthy individuals. Before our knowledge of the microbiome can be utilized and applied in clinical practice, a greater understanding of the 'healthy' microbiome must be achieved. In particular, we must first appreciate how our microbes influence our biology to promote a healthy pregnancy or alternately render preterm birth.
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Microbiota , Nacimiento Prematuro/microbiología , Femenino , Humanos , Lactobacillus/metabolismo , Estudios Longitudinales , Placenta/microbiología , Embarazo , Vagina/microbiologíaRESUMEN
The human microbiome acquires its vastness and diversity over a relatively short time period during development. Much is unknown, however, about the precise prenatal versus postnatal timing or its sources and determinants. Given early evidence of a role for influences during pregnancy and early neonatal and infant life on the microbiome and subsequent metabolic health, research investigating the development and shaping of the microbiome in the fetus and neonate is an important arena for study. This article reviews the relevant available literature and future questions on what shapes the microbiome during early development and mechanisms for doing so.
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Enfermedades Fetales/microbiología , Salud del Lactante , Enfermedades del Recién Nacido/microbiología , Salud Materna , Microbiota/fisiología , Nacimiento Prematuro/microbiología , Adulto , Femenino , Humanos , Recién Nacido , Enfermedades del Recién Nacido/terapia , Masculino , Microbiota/inmunología , Atención Perinatal/métodos , Embarazo , Atención Prenatal/métodos , Probióticos/administración & dosificaciónRESUMEN
BACKGROUND: We have recently shown in both non-human primates and in rodents that fetal and neonatal hepatic expression of the circadian transcription factor, Npas2, is modulated by a high fat maternal diet and plays a critical role in establishing life-long metabolic homeostasis. Similarly, we and others have also established the importance of the maternal and early postnatal diet on establishment of the early gut microbiome. OBJECTIVE: We hypothesized that altered circadian gene expression solely in the neonatal liver would result in gut microbiome dysbiosis, especially with diet-induced metabolic stress (ie, restricted feeding). Using a murine model in which we conditionally knock out Npas2 in the neonatal liver, we aimed to determine the role of the circadian machinery in gut dysbiosis with restricted feeding. STUDY DESIGN: We collected fecal samples from liver Npas2 conditional knockout (n = 11) and wild-type (n = 13) reproductive-aged mice before (study day 0) and after the restricted feeding study (study day 17). Extracted DNA was sequenced using the MiSeq Illumina platform using primers specific for the V4 region of the 16S ribosomal DNA gene. The resulting sequences were quality filtered, aligned, and assigned taxonomy. Principal coordinate analysis was performed on unweighted and weighted UniFrac distances between samples with a permutation analysis of variance to assess clustering significance between groups. Microbial taxa that significantly differ between groups of interest was determined using linear discriminate analysis effect size and randomForrest. RESULTS: Principal coordinate analysis performed on weighted UniFrac distances between male conditional knockout and wild-type cohorts revealed that the gut microbiome of the mice did not differ by genotype at the start of the restricted feeding study but did differ by virtue of genotype at the end of the study (P = .001). Moreover, these differences could be at least partially attributed to restricted feeding-associated alterations in relative abundance of the Bacteroides genus, which has been implicated as crucial to establishing a healthy gut microbiome early in development. CONCLUSION: Here we have provided an initial key insight into the interplay between neonatal establishment of the peripheral circadian clock in the liver and the ability of the gut microbiome to respond to dietary and metabolic stress. Because Npas2 expression in the liver is a target of maternal high-fat diet-induced metabolic perturbations during fetal development, we speculate that these findings have potential implications in the long-term metabolic health of their offspring.
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Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Dieta , Microbioma Gastrointestinal/genética , Proteínas del Tejido Nervioso/genética , Animales , Animales Recién Nacidos , Ritmo Circadiano , Femenino , Regulación de la Expresión Génica , Masculino , RatonesRESUMEN
BACKGROUND: The US Preventive Services Task Force recommends low-dose aspirin for the prevention of preeclampsia among women at high risk for primary occurrence or recurrence of disease. Recommendations for the use of aspirin for preeclampsia prevention were issued by the US Preventive Services Task Force in September 2014. OBJECTIVES: The objective of the study was to evaluate the incidence of recurrent preeclampsia in our cohort before and after the US Preventive Services Task Force recommendation for aspirin for preeclampsia prevention. STUDY DESIGN: This was a retrospective cohort study designed to evaluate the rates of recurrent preeclampsia among women with a history of preeclampsia. We utilized a 2-hospital, single academic institution database from August 2011 through June 2016. We excluded multiple gestations and included only the first delivery for women with multiple deliveries during the study period. The cohort of women with a history of preeclampsia were divided into 2 groups, before and after the release of the US Preventive Services Task Force 2014 recommendations. Potential confounders were accounted for in multivariate analyses, and relative risk and adjusted relative risk were calculated. RESULTS: A total of 17,256 deliveries occurred during the study period. A total of 417 women had a documented history of prior preeclampsia: 284 women before and 133 women after the US Preventive Services Task Force recommendation. Comparing the before and after groups, the proportion of Hispanic women in the after group was lower and the method of payment differed between the groups (P <.0001). The prevalence of type 1 diabetes was increased in the after period, but overall rates of pregestational diabetes were similar (6.3% before vs 5.3% after [P > .05]). Risk factors for recurrent preeclampsia included maternal age >35 years (relative risk, 1.83; 95% confidence interval, 1.34-2.48), Medicaid insurance (relative risk, 2.08; 95% confidence interval, 1.15-3.78), type 2 diabetes (relative risk, 2.13; 95% confidence interval, 1.37-3.33), and chronic hypertension (relative risk, 1.96; 95% confidence interval, 1.44-2.66). The risk of recurrent preeclampsia was decreased by 30% in the after group (adjusted relative risk, 0.70; 95% confidence interval, 0.52-0.95). CONCLUSION: Rates of recurrent preeclampsia among women with a history of preeclampsia decreased by 30% after release of the US Preventive Services Task Force recommendation for aspirin for preeclampsia prevention. Future prospective studies should include direct measures of aspirin compliance, gestational age at initiation, and explore the influence of race and ethnicity on the efficacy of this primary prevention.
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Antiinflamatorios no Esteroideos/administración & dosificación , Aspirina/administración & dosificación , Preeclampsia/prevención & control , Adulto , Estudios de Cohortes , Diabetes Mellitus Tipo 2/complicaciones , Femenino , Adhesión a Directriz , Humanos , Hipertensión/complicaciones , Edad Materna , Medicaid , Guías de Práctica Clínica como Asunto , Embarazo , Recurrencia , Estudios Retrospectivos , Factores de Riesgo , Estados UnidosRESUMEN
Human microbial communities are characterized by their taxonomic, metagenomic and metabolic diversity, which varies by distinct body sites and influences human physiology. However, when and how microbial communities within each body niche acquire unique taxonomical and functional signatures in early life remains underexplored. We thus sought to determine the taxonomic composition and potential metabolic function of the neonatal and early infant microbiota across multiple body sites and assess the effect of the mode of delivery and its potential confounders or modifiers. A cohort of pregnant women in their early third trimester (n = 81) were prospectively enrolled for longitudinal sampling through 6 weeks after delivery, and a second matched cross-sectional cohort (n = 81) was additionally recruited for sampling once at the time of delivery. Samples across multiple body sites, including stool, oral gingiva, nares, skin and vagina were collected for each maternal-infant dyad. Whole-genome shotgun sequencing and sequencing analysis of the gene encoding the 16S rRNA were performed to interrogate the composition and function of the neonatal and maternal microbiota. We found that the neonatal microbiota and its associated functional pathways were relatively homogeneous across all body sites at delivery, with the notable exception of the neonatal meconium. However, by 6 weeks after delivery, the infant microbiota structure and function had substantially expanded and diversified, with the body site serving as the primary determinant of the composition of the bacterial community and its functional capacity. Although minor variations in the neonatal (immediately at birth) microbiota community structure were associated with the cesarean mode of delivery in some body sites (oral gingiva, nares and skin; R2 = 0.038), this was not true for neonatal stool (meconium; Mann-Whitney P > 0.05), and there was no observable difference in community function regardless of delivery mode. For infants at 6 weeks of age, the microbiota structure and function had expanded and diversified with demonstrable body site specificity (P < 0.001, R2 = 0.189) but without discernable differences in community structure or function between infants delivered vaginally or by cesarean surgery (P = 0.057, R2 = 0.007). We conclude that within the first 6 weeks of life, the infant microbiota undergoes substantial reorganization, which is primarily driven by body site and not by mode of delivery.
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Cesárea , Parto Obstétrico , Microbioma Gastrointestinal/genética , ARN Ribosómico 16S/genética , Adulto , Estudios Transversales , Femenino , Encía/microbiología , Humanos , Lactante , Recién Nacido , Estudios Longitudinales , Masculino , Meconio/microbiología , Metagenómica , Mucosa Nasal/microbiología , Embarazo , Tercer Trimestre del Embarazo , Estudios Prospectivos , Piel/microbiología , Adulto JovenRESUMEN
Evidence supporting the Developmental Origins of Health and Disease Hypothesis indicates that maternal nutrition in pregnancy has a significant impact on offspring disease risk later in life, likely by modulating developmental processes in utero. Gut microbiota have recently been explored as a potential mediating factor, as dietary components strongly influence microbiota abundance, function and its impact on host physiology. A growing body of evidence has additionally indicated that the intrauterine environment is not sterile as once presumed, indicating that maternal-fetal transmission of microbiota may occur during pregnancy. In this article, we will review the body of literature that supports this emerging hypothesis, as well as highlight the work in relevant animal models demonstrating associations with maternal gestational nutrition and the offspring gut microbiome that may influence offspring physiology and susceptibility to disease.
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Desarrollo Fetal , Microbioma Gastrointestinal , Fenómenos Fisiologicos Nutricionales Maternos , Animales , Femenino , Humanos , Lactancia , Masculino , Intercambio Materno-Fetal , EmbarazoRESUMEN
BACKGROUND: Emerging evidence suggests that the in utero environment is not sterile as once presumed. Work in the mouse demonstrated transmission of commensal bacteria from mother to fetus during gestation, though it is unclear what modulates this process. We have previously shown in the nonhuman primate that, independent of obesity, a maternal high-fat diet during gestation and lactation persistently shapes the juvenile gut microbiome. We therefore sought to interrogate in a population-based human longitudinal cohort whether a maternal high-fat diet similarly alters the neonatal and infant gut microbiome in early life. METHODS: A representative cohort was prospectively enrolled either in the early third trimester or intrapartum (n = 163), with a subset consented to longitudinal sampling through the postpartum interval (n = 81). Multiple body site samples, including stool and meconium, were collected from neonates at delivery and by 6 weeks of age. A rapid dietary questionnaire was administered to estimate intake of fat, added sugars, and fiber over the past month (National Health and Examination Survey). DNA was extracted from each infant meconium/stool sample (MoBio) and subjected to 16S rRNA gene sequencing and analysis. RESULTS: On average, the maternal dietary intake of fat ranged from 14.0 to 55.2 %, with an average intake of 33.1 % (σ = 6.1 %). Mothers whose diets significantly differed from the mean (±1 standard deviation) were separated into two distinct groups, a control group (n = 13, µ = 24.4 %) and a high-fat group (n = 13, µ = 43.1 %). Principal coordinate analysis revealed that the microbiome of the neonatal stool at birth (meconium) clustered differently by virtue of maternal gestational diet (PERMANOVA p = 0.001). LEfSe feature selection identified several taxa that discriminated the groups, with a notable relative depletion of Bacteroides in the neonates exposed to a maternal high-fat gestational diet (Student's t-test, p < 0.05) that persisted to 6 weeks of age. CONCLUSIONS: Similar to the primate, independent of maternal body mass index, a maternal high-fat diet is associated with distinct changes in the neonatal gut microbiome at birth which persist through 4-6 weeks of age. Our findings underscore the importance of counseling pregnant mothers on macronutrient consumption during pregnancy and lactation.
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Dieta Alta en Grasa , Grasas de la Dieta/administración & dosificación , Microbioma Gastrointestinal/efectos de los fármacos , Meconio/microbiología , ARN Ribosómico 16S/genética , Femenino , Microbioma Gastrointestinal/genética , Humanos , Lactante , Recién Nacido , Embarazo , Tercer Trimestre del Embarazo , Estudios Prospectivos , Encuestas y CuestionariosAsunto(s)
Trastornos del Crecimiento/dietoterapia , Trastornos del Crecimiento/microbiología , Intestinos/microbiología , Desnutrición/dietoterapia , Desnutrición/microbiología , Microbiota/fisiología , Animales , Preescolar , Enfermedad Crónica , Clostridium symbiosum/aislamiento & purificación , Clostridium symbiosum/fisiología , Dieta/efectos adversos , Dieta/métodos , Heces/microbiología , Femenino , Vida Libre de Gérmenes , Trastornos del Crecimiento/etiología , Voluntarios Sanos , Humanos , Lactante , Intestinos/efectos de los fármacos , Hígado/metabolismo , Malaui , Desnutrición/complicaciones , Ratones , Microbiota/efectos de los fármacos , Microbiota/genética , Leche Humana/química , Leche Humana/microbiología , Madres , Oligosacáridos/análisis , Oligosacáridos/farmacología , Oligosacáridos/uso terapéutico , Ruminococcus/aislamiento & purificación , Ruminococcus/fisiología , Somatomedinas/biosíntesis , Aumento de Peso/efectos de los fármacosRESUMEN
Metabolic syndrome (MetS), following intrauterine growth restriction (IUGR), is epigenetically heritable. Recently, we abrogated the F2 adult phenotype with essential nutrient supplementation (ENS) of intermediates along the 1-carbon pathway. With the use of the same grandparental uterine artery ligation model, we profiled the F2 serum metabolome at weaning [postnatal day (d)21; n = 76] and adulthood (d160; n = 12) to test if MetS is preceded by alterations in the metabolome. Indicative of developmentally programmed MetS, adult F2, formerly IUGR rats, were obese (621 vs. 461 g; P < 0.0001), dyslipidemic (133 vs. 67 mg/dl; P < 0.001), and glucose intolerant (26 vs. 15 mg/kg/min; P < 0.01). Unbiased gas chromatography-mass spectrometry (GC-MS) profiling revealed 34 peaks corresponding to 12 nonredundant metabolites and 9 unknowns to be changing at weaning [false discovery rate (FDR) < 0.05]. Markers of later-in-life MetS included citric acid, glucosamine, myoinositol, and proline (P < 0.03). Hierarchical clustering revealed grouping by IUGR lineage and supplementation at d21 and d160. Weanlings grouped distinctly for ENS and IUGR by partial least-squares discriminate analysis (PLS-DA; P < 0.01), whereas paternal and maternal IUGR (IUGR(pat)/IUGR(mat), respectively) control-fed rats, destined for MetS, had a distinct metabolome at weaning (randomForest analysis; class error < 0.1) and adulthood (PLS-DA; P < 0.05). In sum, we have found that alterations in the metabolome accompany heritable IUGR, precede adult-onset MetS, and are partially amenable to dietary intervention.
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Retardo del Crecimiento Fetal/metabolismo , Síndrome Metabólico/metabolismo , Metaboloma , Metabolómica/métodos , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Animales Recién Nacidos , Peso Corporal , Ácido Cítrico/sangre , Ácido Cítrico/metabolismo , Suplementos Dietéticos , Dislipidemias/sangre , Dislipidemias/genética , Dislipidemias/metabolismo , Femenino , Retardo del Crecimiento Fetal/sangre , Retardo del Crecimiento Fetal/genética , Cromatografía de Gases y Espectrometría de Masas , Glucosamina/sangre , Glucosamina/metabolismo , Intolerancia a la Glucosa/sangre , Intolerancia a la Glucosa/genética , Intolerancia a la Glucosa/metabolismo , Masculino , Síndrome Metabólico/sangre , Síndrome Metabólico/genética , Obesidad/sangre , Obesidad/genética , Obesidad/metabolismo , Ratas Sprague-Dawley , DesteteRESUMEN
The human microbiome, the collective genome of the microbial community that is on and within us, has recently been mapped. The initial characterization of healthy subjects has provided investigators with a reference population for interrogating the microbiome in metabolic, intestinal, and reproductive health and disease states. Although it is known that bacteria can colonize the vagina, recent metagenomic studies have shown that the vaginal microbiome varies among reproductive age women. Similarly, the richness and diversity of intestinal microbiota also naturally fluctuate among gravidae in both human and nonhuman primates, as well as mice. Moreover, recent evidence suggests that microbiome niches in pregnancy are not limited to maternal body sites, as the placenta appears to harbor a low biomass microbiome that is presumptively established in early pregnancy and varies in association with a remote history of maternal antenatal infection as well as preterm birth. In this article, we will provide a brief overview on metagenomics science as a means to investigate the microbiome, observations pertaining to both variation and the presumptive potential role of a varied microbiome during pregnancy, and how future studies of the microbiome in pregnancy may lend to a better understanding of human biology, reproductive health, and parturition.
Asunto(s)
Metagenómica/métodos , Microbiota/fisiología , Complicaciones Infecciosas del Embarazo/microbiología , Vagina/microbiología , Animales , ADN Bacteriano/genética , Femenino , Estudio de Asociación del Genoma Completo , Humanos , Recién Nacido , Transmisión Vertical de Enfermedad Infecciosa , Ratones , Microbiota/genética , Placenta/microbiología , Embarazo , Salud ReproductivaRESUMEN
The causes of preterm birth are multifactorial, but its association with infection has been well-established. The predominant paradigm describes an ascending infection from the lower genital tract through the cervix and into the presumably sterile fetal membranes and placenta. Thus, an evaluation of the role of the vaginal microbiome in preterm birth is implicated. However, emerging fields of data described in this review suggest that the placenta might not be sterile, even in the absence of clinical infection. We thus propose an additional mechanism for placental colonization and infection: hematogenous spread. When considered in the context of decades of evidence demonstrating a strong risk of recurrence for preterm birth, studies on parturition are ideal for applying the rapidly expanding field of metagenomics and analytic pipelines. The translational implications toward identification of innovative treatments for the prevention of preterm birth are further discussed. In sum, exciting advances in understanding the role of both host and microbiota in parturition and preterm birth are on the horizon.