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1.
Am J Clin Nutr ; 110(3): 769-779, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31274142

RESUMO

Nationally representative data from mother-child dyads that capture human milk composition (HMC) and associated health outcomes are important for advancing the evidence to inform federal nutrition and related health programs, policies, and consumer information across the governments in the United States and Canada as well as in nongovernment sectors. In response to identified gaps in knowledge, the National Institute of Diabetes and Digestive and Kidney Diseases of the NIH sponsored the "Workshop on Human Milk Composition-Biological, Environmental, Nutritional, and Methodological Considerations" held 16-17 November 2017 in Bethesda, Maryland. Through presentations and discussions, the workshop aimed to 1) share knowledge on the scientific need for data on HMC; 2) explore the current understanding of factors affecting HMC; 3) identify methodological challenges in human milk (HM) collection, storage, and analysis; and 4) develop a vision for a research program to develop an HMC data repository and database. The 4 workshop sessions included 1) perspectives from both federal agencies and nonfederal academic experts, articulating scientific needs for data on HMC that could lead to new research findings and programmatic advances to support public health; 2) information about the factors that influence lactation and/or HMC; 3) considerations for data quality, including addressing sampling strategies and the complexities in standardizing collection, storage, and analyses of HM; and 4) insights on how existing research programs and databases can inform potential visions for HMC initiatives. The general consensus from the workshop is that the limited scope of HM research initiatives has led to a lack of robust estimates of the composition and volume of HM consumed and, consequently, missed opportunities to improve maternal and infant health.

2.
Breastfeed Med ; 14(7): 465-474, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31210534

RESUMO

Background: Breastfeeding promotion and support are not universally accepted in the United States as a strategy to reduce infant mortality. We investigated associations between breastfeeding and infant mortality in an urban population with high infant mortality and low breastfeeding rates. Methods: A retrospective epidemiologic study linked birth-infant death data for 148,679 live births in Shelby County, Tennessee from January 2004 to December 2014. Births <500 g, deaths ≤7 days, deaths because of congenital anomalies or malignant neoplasms, and records with missing breastfeeding status were excluded. Main outcomes were infant death before the first birthday, neonatal death <28 days, and postneonatal death ≥28 days by ever or never breastfed. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for breastfeeding initiation were adjusted for maternal factors and infant factors. Results: Initiation of breastfeeding was associated with a significant reduction in total infant mortality (OR = 0.81, 95% CI = 0.68-0.97, p = 0.023). Neonatal mortality was also significantly reduced with any breastfeeding (OR = 0.49, 95% CI = 0.34-0.72, p = 0.001). Postneonatal mortality was not significantly associated with breastfeeding initiation in the overall population (OR = 0.95, 95% CI = 0.78-1.17, p = 0.65), but was significant in the nonblack population (OR = 0.63, 95% CI = 0.41-0.98, p = 0.039). An association was observed between breastfeeding initiation and infant mortality from infectious disease (OR = 0.49, 95% CI = 0.32-0.77, p = 0.002). Conclusions: In an urban area with high infant mortality and low breastfeeding rates, initiation of breastfeeding was significantly associated with reductions in overall infant mortality, neonatal mortality, and infection-related deaths. Breastfeeding promotion, protection, and support should be an integral strategy of infant mortality reduction initiatives.

3.
J Pediatr Gastroenterol Nutr ; 69(3): 388-392, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31058771

RESUMO

Maternal supplementation with 1000 mg/day docosahexaenoic acid (DHA) provides third trimester DHA accretion levels in breast milk for the preterm infant. We hypothesized that DHA supplementation to mothers providing breastmilk for extremely preterm infants would result in decreased inflammatory markers, in the infant. Mother/infant dyads (n = 27) were enrolled at birth and mothers were assigned to receive 200 or 1000 mg/day of DHA. Milk and plasma samples were analyzed for fatty acids and inflammatory markers. Decreases in inflammation were observed in both maternal and infant plasma and correlated with red blood cell (RBC) DHA levels. The fact that maternal DHA supplementation decreases infant markers of inflammation implies that DHA, delivered through breastmilk, has the potential to decrease inflammation in the infant.

4.
Breastfeed Med ; 14(3): 193-202, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30916575

RESUMO

OBJECTIVE: Human milk administration in the early peritransplant period would lower intestinal inflammation after bone marrow transplant (BMT). MATERIALS AND METHODS: Children 0-5 years undergoing BMT received either a ready-to-feed human milk preparation designed for these children (Prolacta Bioscience, Duarte, CA) or standard formula. Babies breastfeeding at the time of BMT were also enrolled on the human milk arm. Human milk was administered from day -3 until day +14 after BMT. Metagenomic shotgun sequencing and metabolomics of stool, plasma cytokines, and regenerating islet-derived 3α (REG3α) levels were measured at enrollment and day +14. Human leukocyte antigen-DR isotype (HLA-DR), CD38, and CD69 expression on T cells were evaluated at day +21. RESULTS: Forty-six children were enrolled, 32 received human milk (donor milk n = 23, breastfeeding babies n = 9), and 14 were controls who received standard feeds supervised by a BMT dietician. Twenty-four patients received at least 60% of goal human milk and were evaluable. Plasma interleukin (IL)-8 (p = 0.04), IL-10 (p = 0.02), and REG3α (p = 0.03) were decreased in the human milk cohort. Peripheral blood CD69+ CD8+ T cells were higher in controls (p = 0.01). Species abundance of Adenovirus (p = 0.00034), Escherichia coli (p = 0.0017), Cryptosporidium parvum (p = 0.0006), Dialister invisus (p = 0.01), and Pseudomonas aeruginosa (p = 0.05) from stool was higher in controls. Stool alanine, tyrosine, methionine, and the ratio of fecal alanine to choline and phosphocholine were higher in controls (p < 0.05). No difference was observed in stool propionate and butyrate levels as measures of short-chain fatty acids between the two cohorts. CONCLUSIONS: Administration of human milk resulted in decreased markers of intestinal inflammation and could be a valuable adjunct for patients after BMT.


Assuntos
Transplante de Medula Óssea/efeitos adversos , Nutrição Enteral , Inflamação/prevenção & controle , Intestinos/patologia , Leite Humano , Animais , Bacteriemia/epidemiologia , Bacteriemia/prevenção & controle , Pré-Escolar , Citocinas/metabolismo , Feminino , Microbioma Gastrointestinal , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Lactente , Intestinos/microbiologia , Masculino , Ohio , Projetos Piloto , Cicatrização
5.
Artigo em Inglês | MEDLINE | ID: mdl-30865977

RESUMO

Fatty acids (FAs) and fat-soluble vitamins are vital components of the human milk lipid fraction. About two-thirds of the human milk FA fraction consist of oleic, linoleic, and palmitic FAs, but the precise composition depends on maternal geography, diet, and genetics. Mothers with high fish consumption have more docosahexaenoic acid (DHA) and other ω-3 FAs in their milk, while mothers with high dairy consumption have more branched-chain FAs in their milk. Vitamins A and E are the most common fat-soluble vitamins, but milk concentrations vary, depending on maternal diet and body stores. Vitamin D is typically low or undetectable in mother's milk and typically fails to meet the infant needs. However, trial data indicate that high maternal supplementation (6,400 IU/day) safely provides nutritionally adequate amounts of vitamin D in her milk. FA and fat-soluble vitamin levels in mother's milk can significantly influence infant health; for example, in preterm infants, low endogenous stores of DHA paired with low levels in maternal milk may influence the risk of chronic lung disease and other inflammatory conditions. Greater attention is warranted to the variation in FA and fat-soluble vitamin content of human milk in relation to infant health.

6.
J Infect Dis ; 219(5): 746-749, 2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-30357332

RESUMO

Rotaviruses bind to enterocytes in a genotype-specific manner via histo-blood group antigens (HBGAs), which are also detectable in saliva. We evaluated antirotavirus immunoglobulin A seroconversion ('vaccine take") among 166 Ghanaian infants after 2-3 doses of G1P[8] rotavirus vaccine during a vaccine trial, by HBGA status from saliva collected at age 4.1 years. Only secretor status was associated with seroconversion: 41% seroconversion for secretors vs 13% for nonsecretors; relative risk, 3.2 (95% confidence interval, 1.2-8.1; P = .016). Neither Lewis antigen nor salivary antigen blood type was associated with seroconversion. Likelihood of "take" for any particular rotavirus vaccine may differ across populations based on HBGAs.


Assuntos
Antígenos de Histocompatibilidade/análise , Infecções por Rotavirus/prevenção & controle , Vacinas contra Rotavirus/imunologia , Rotavirus/imunologia , Soroconversão , Pré-Escolar , Feminino , Genótipo , Gana , Humanos , Lactente , Masculino , Vacinas contra Rotavirus/administração & dosagem , Saliva/química
7.
Nutr Clin Pract ; 33(5): 687-693, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29603407

RESUMO

BACKGROUND: Human milk feeding is encouraged for all infants; however, the mammary gland depends on maternal dietary intake of vitamins A, B1, B2, B6, B12, D, docosahexaenoic acid (DHA), choline, and iodine. Nutrition support team knowledge of maternal feeding guidelines for these nutrient sources can therefore impact infant intake. We hypothesized that these key nutrients for lactation in the mother's diet would be less than the dietary guidelines in the United States. METHODS: This was a secondary analysis of nutrition data collected during a randomized, controlled trial. Dietary records were analyzed from 16 mothers (13 with singleton and 3 with multiple births) completing the study. Mean dietary intakes of selected nutrients were calculated and compared with the current dietary reference intakes. RESULTS: Mean maternal dietary intake for singletons was significantly (P < .05) lower than the dietary reference intakes for (vitamin A (58%), vitamin D (44%), and choline (58%);) DHA comprised only 5% of the current expert recommendation. Based on singleton recommendations, mothers to twins consumed an adequate intake except for DHA. CONCLUSIONS: Women providing breast milk for singleton preterm infants did not consume dietary reference intakes for key nutrients. Twin mothers' diets were adequate except for DHA, but these guidelines are based on singleton pregnancies and remain poorly understood for twin needs. The nutrition support team can have a unique role in maternal dietary education to impact human milk nutrient delivery to the infant.


Assuntos
Dieta/normas , Lactação/fisiologia , Leite Humano , Política Nutricional , Estado Nutricional/fisiologia , Adulto , Aleitamento Materno , Colina/análise , Registros de Dieta , Ácidos Docosa-Hexaenoicos/análise , Feminino , Fidelidade a Diretrizes , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Fenômenos Fisiológicos da Nutrição Materna , Ensaios Clínicos Controlados Aleatórios como Assunto , Gêmeos , Estados Unidos , Vitamina A/análise , Vitamina D/análise
8.
J Pediatr ; 197: 97-103.e3, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29551319

RESUMO

OBJECTIVES: We examined the impact of prenatal exposure to maternal antibiotics on risk of necrotizing enterocolitis (NEC), late onset sepsis (LOS), and death in infants born preterm. STUDY DESIGN: Secondary data analysis was conducted via an extant cohort of 580 infants born <32 weeks of gestation and enrolled in 3 level III neonatal intensive care units. Prenatal antibiotic exposure was defined as antibiotics received by the mother within 72 hours before delivery. Postnatal empiric antibiotic exposure was defined as antibiotic initiated within the first day of life without documented infection, categorized as low (<5 days) or high (>5 days) duration. RESULTS: Two-thirds of mothers received antibiotics within 72 hours before delivery, of whom 59.8% received >1 antibiotic. Ampicillin (37.6%) and azithromycin (26.4%) were the most common antibiotics given. NEC occurred in 7.5%, LOS in 11.1%, death in 9.6%, and the combined outcome of NEC, LOS, or death in 21.3% of study infants. In multiple logistic regression models adjusted for gestational age, postnatal empiric antibiotic exposure, and other factors, prenatal antibiotic exposure was associated with reduced risk of NEC (OR 0.28; 95% CI 0.14-0.56; P < .001), death (OR 0.29; 95% CI 0.14-0.60; P = .001), but not LOS (OR 1.59; 95% CI 0.84-2.99; P = .15), although protection was significant for the combined outcome (OR 0.52, P < .001). High postnatal empiric antibiotic exposure was associated with greater risk of death but not other outcomes in multiple regression models (OR 3.18, P = .002). CONCLUSIONS: Prenatal antibiotic exposure was associated with lower rates of NEC or death of infants born preterm, and its impact on infant outcomes warrants further study.


Assuntos
Antibacterianos/efeitos adversos , Enterocolite Necrosante/epidemiologia , Mortalidade Infantil , Sepse Neonatal/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Adolescente , Adulto , Enterocolite Necrosante/etiologia , Feminino , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Unidades de Terapia Intensiva Neonatal , Masculino , Sepse Neonatal/etiologia , Gravidez , Estudos Prospectivos , Fatores de Risco , Estados Unidos , Adulto Jovem
9.
Microbiome ; 5(1): 31, 2017 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-28274256

RESUMO

BACKGROUND: Necrotizing enterocolitis (NEC) is a catastrophic disease of preterm infants, and microbial dysbiosis has been implicated in its pathogenesis. Studies evaluating the microbiome in NEC and preterm infants lack power and have reported inconsistent results. METHODS AND RESULTS: Our objectives were to perform a systematic review and meta-analyses of stool microbiome profiles in preterm infants to discern and describe microbial dysbiosis prior to the onset of NEC and to explore heterogeneity among studies. We searched MEDLINE, PubMed, CINAHL, and conference abstracts from the proceedings of Pediatric Academic Societies and reference lists of relevant identified articles in April 2016. Studies comparing the intestinal microbiome in preterm infants who developed NEC to those of controls, using culture-independent molecular techniques and reported α and ß-diversity metrics, and microbial profiles were included. In addition, 16S ribosomal ribonucleic acid (rRNA) sequence data with clinical meta-data were requested from the authors of included studies or searched in public data repositories. We reprocessed the 16S rRNA sequence data through a uniform analysis pipeline, which were then synthesized by meta-analysis. We included 14 studies in this review, and data from eight studies were available for quantitative synthesis (106 NEC cases, 278 controls, 2944 samples). The age of NEC onset was at a mean ± SD of 30.1 ± 2.4 weeks post-conception (n = 61). Fecal microbiome from preterm infants with NEC had increased relative abundances of Proteobacteria and decreased relative abundances of Firmicutes and Bacteroidetes prior to NEC onset. Alpha- or beta-diversity indices in preterm infants with NEC were not consistently different from controls, but we found differences in taxonomic profiles related to antibiotic exposure, formula feeding, and mode of delivery. Exploring heterogeneity revealed differences in microbial profiles by study and the target region of the 16S rRNA gene (V1-V3 or V3-V5). CONCLUSIONS: Microbial dysbiosis preceding NEC in preterm infants is characterized by increased relative abundances of Proteobacteria and decreased relative abundances of Firmicutes and Bacteroidetes. Microbiome optimization may provide a novel strategy for preventing NEC.


Assuntos
Disbiose , Enterocolite Necrosante/microbiologia , Fezes/microbiologia , Microbioma Gastrointestinal , Intestinos/fisiopatologia , Bactérias/isolamento & purificação , Bacteroides/genética , Bacteroides/isolamento & purificação , Firmicutes/genética , Firmicutes/isolamento & purificação , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Doenças do Prematuro , Intestinos/microbiologia , Proteobactérias/genética , Proteobactérias/isolamento & purificação , RNA Ribossômico 16S
10.
Nutrients ; 9(3)2017 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-28335478

RESUMO

BACKGROUND: Mother's own milk is the first choice for feeding preterm infants, but when not available, pasteurized human donor milk (PDM) is often used. Infants fed PDM have difficulties maintaining appropriate growth velocities. To assess the most basic elements of nutrition, we tested the hypotheses that fatty acid and amino acid composition of PDM is highly variable and standard pooling practices attenuate variability; however, total nutrients may be limiting without supplementation due to late lactational stage of the milk. METHODS: A prospective cross-sectional sampling of milk was obtained from five donor milk banks located in Ohio, Michigan, Colorado, Texas-Ft Worth, and California. Milk samples were collected after Institutional Review Board (#07-0035) approval and informed consent. Fatty acid and amino acid contents were measured in milk from individual donors and donor pools (pooled per Human Milk Banking Association of North America guidelines). Statistical comparisons were performed using Kruskal-Wallis, Spearman's, or Multivariate Regression analyses with center as the fixed factor and lactational stage as co-variate. RESULTS: Ten of the fourteen fatty acids and seventeen of the nineteen amino acids analyzed differed across Banks in the individual milk samples. Pooling minimized these differences in amino acid and fatty acid contents. Concentrations of lysine and docosahexaenoic acid (DHA) were not different across Banks, but concentrations were low compared to recommended levels. CONCLUSIONS: Individual donor milk fatty acid and amino acid contents are highly variable. Standardized pooling practice reduces this variability. Lysine and DHA concentrations were consistently low across geographic regions in North America due to lactational stage of the milk, and thus not adequately addressed by pooling. Targeted supplementation is needed to optimize PDM, especially for the preterm or volume restricted infant.


Assuntos
Lactação , Bancos de Leite , Leite Humano/química , Valor Nutritivo , Pasteurização , Adulto , Aminoácidos/análise , Estudos Transversais , Ácidos Docosa-Hexaenoicos/análise , Ácidos Graxos/análise , Feminino , Humanos , Lactente , Lisina/análise , Proteínas do Leite/análise , América do Norte , Estudos Prospectivos , Adulto Jovem
11.
J Infect Dis ; 215(5): 786-789, 2017 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-28329092

RESUMO

Histo-blood group antigens (HBGAs) expressed on enterocytes are proposed receptors for rotaviruses and can be measured in saliva. Among 181 Pakistani infants in a G1P[8] rotavirus vaccine trial who were seronegative at baseline, anti-rotavirus immunoglobulin A seroconversion rates after 3 vaccine doses differed significantly by salivary HBGA phenotype, with the lowest rate (19%) among infants who were nonsecretors (ie, who did not express the carbohydrate synthesized by FUT2), an intermediate rate (30%) among secretors with non-blood group O, and the highest rate (51%) among secretors with O blood group. Differences in HBGA expression may be responsible for some of the discrepancy in the level of protection detected for the current rotavirus vaccines in low-income versus high-income settings.


Assuntos
Sistema ABO de Grupos Sanguíneos/sangue , Infecções por Rotavirus/prevenção & controle , Vacinas contra Rotavirus/administração & dosagem , Anticorpos Antivirais/sangue , Antígenos Virais/sangue , Humanos , Imunoglobulina A/sangue , Imunoglobulina A/imunologia , Lactente , Paquistão , Fenótipo , Rotavirus , Infecções por Rotavirus/imunologia , Vacinas contra Rotavirus/uso terapêutico , Saliva/imunologia , Saliva/virologia
12.
Matern Child Health J ; 21(6): 1367-1376, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28138825

RESUMO

Objective Obesity in adults is associated with inflammation and oxidative stress. Whether or not this phenotype is reflected in human milk (HM) composition, or may impact infant growth remains unknown. We investigated whether HM from overweight/obese (OW/Ob) mothers exhibited higher concentrations of inflammatory cytokines and markers of oxidative stress. We also correlated these bioactive components with infant growth patterns. Methods This was an observational cohort of 56 breastfeeding mothers and their infants [33 normal weight (NW) and 23 OW/Ob]. Infants were followed until 6 months of age and HM collected at 2-weeks and 4-months. Results Markers of oxidative stress, 8-hydroxy-deoxyguanosine (8OHdG) and 4-hydroxynonenol (HNE), decreased in HM over time (p < 0.001) and did not differ between NW and OW/Ob women. Concentrations of inflammatory cytokines, IL-6, IL-8, and TNF-α, were all inter-correlated (p < 0.001) but did not differ between NW and OW/Ob women. HM fat, protein, lactose, and total calories did not differ between NW and OW/Ob women. Infant growth patterns did not differ by group. In a model of infant weight-for-length-Z score trajectory, there was a significant interaction between both lactose and 8OHdG with maternal group: HM lactose and 8OHdG concentrations were both positively associated with increases in WLZ trajectory only among infants breastfed by OW/Ob mothers. Conclusions for Practice HM composition was relatively stable between NW and OW/Ob women. In exclusively breastfed infants, HM concentrations of lactose and 8OHdG, a marker of oxidative stress, may contribute to regulation of infant weight gain, especially among infants of OW/Ob women.


Assuntos
Biomarcadores/análise , Índice de Massa Corporal , Leite Humano/química , Mães , Aleitamento Materno , Desenvolvimento Infantil , Pré-Escolar , Estudos de Coortes , Citocinas/análise , Feminino , Humanos , Lactente , Lactação/fisiologia , Estudos Longitudinais , Obesidade/metabolismo , Obesidade/fisiopatologia , Sobrepeso/fisiopatologia , Estresse Oxidativo
13.
Am J Clin Nutr ; 105(1): 177-184, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27903517

RESUMO

BACKGROUND: An understudied component of the diet, branched-chain fatty acids (BCFAs) are distinctive saturated fatty acids that may have an important influence on health. Human-milk fatty acid composition is known to differ worldwide, but comparative data are lacking on BCFAs. OBJECTIVE: We tested the hypotheses that concentrations of BCFAs in human milk differ between populations and are associated with maternal diet. DESIGN: We surveyed the BCFA composition of samples collected as part of a standardized, prospective study of human-milk composition. Mothers were enrolled from 3 urban populations with differing diets: Cincinnati, Ohio; Shanghai, China; and Mexico City, Mexico. Enrollment was limited to healthy mothers of term singleton infants. We undertook a cross-sectional analysis of milk from all women with samples at postpartum week 4 (n = 359; ∼120 women/site). Fatty acids were extracted from milk by using a modified Bligh-Dyer technique and analyzed by gas chromatography. Statistical analysis was performed by ANOVA and Tobit regression. For Cincinnati mothers, 24-h diet recalls were analyzed in relation to the individual BCFA concentrations measured in milk samples. RESULTS: Total BCFAs in milk differed by site, with the highest concentration in Cincinnati followed by Mexico City and Shanghai (mean ± SE: 7.90 ± 0.41, 6.10 ± 0.36, and 4.27 ± 0.25 mg/100 mL, respectively; P < 0.001). Site differences persisted after delivery mode, maternal age, and body mass index were controlled for. The individual concentrations of iso-14:0, iso-16:0, iso-18:0, anteiso-15:0, and anteiso-17:0 also differed between sites. Milk concentrations of iso-14:0 and anteiso-15:0 were associated with maternal intake of dairy; iso-16:0 was associated with maternal intakes of dairy and beef. CONCLUSIONS: BCFA concentrations in milk at 4 wk postpartum differed between mothers from Cincinnati, Shanghai, and Mexico City. Variations in human-milk BCFAs are influenced by diet. The impact of BCFAs on infant health warrants investigation.


Assuntos
Dieta , Ácidos Graxos/análise , Comportamento Alimentar , Lactação/metabolismo , Leite Humano/química , China , Estudos Transversais , Laticínios , Feminino , Humanos , Recém-Nascido , Masculino , Carne , México , Ohio , Gravidez , Estudos Prospectivos
14.
PLoS One ; 11(9): e0162734, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27658190

RESUMO

OBJECTIVE: Chorioamnionitis (inflammation of the placenta and fetal membranes) and abnormal gastrointestinal colonization have been associated with an increased risk of sepsis and death in preterm infants, but whether chorioamnionitis causes abnormal pioneering gastrointestinal colonization in infants is not known. We determined the relationship between chorioamnionitis, altered infant fecal microbiome indicating abnormal gastrointestinal colonization, and adverse outcomes. STUDY DESIGN: Preterm infants ≤ 28 weeks at birth were enrolled from 3 level III NICUs in Cincinnati, Ohio and Birmingham, Alabama. Sequencing for 16S microbial gene was performed on stool samples in the first 3 weeks of life. Chorioamnionitis was diagnosed by placental histology. Late onset sepsis and death outcomes were analyzed in relation to fecal microbiota and chorioamnionitis with or without funisitis (inflammation of the umbilical cord). RESULTS: Of the 106 enrolled infants, 48 infants had no chorioamnionitis, 32 infants had chorioamnionitis but no funisitis (AC), and 26 infants had chorioamnionitis with funisitis (ACF). The fecal samples from ACF infants collected by day of life 7 had higher relative abundance of family Mycoplasmataceae (phylum Tenericutes), genus Prevotella (phylum Bacteroidetes) and genus Sneathia (phylum Fusobacteria). Further, AC and ACF infants had higher incidence of late-onset sepsis/death as a combined outcome. Presence of specific clades in fecal samples, specifically, order Fusobacteria, genus Sneathia or family Mycoplasmataceae, were significantly associated with higher risk of sepsis or death. CONCLUSION: The results support the hypothesis that specific alterations in the pioneering infant gastrointestinal microbiota induced by chorioamnionitis predispose to neonatal sepsis or death.

15.
J Pediatric Infect Dis Soc ; 5(2): 210-3, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27199472

RESUMO

Qualitative polymerase chain reaction (PCR) was used to determine the prevalence of fecal excretion of BK virus, JC virus, and simian virus 40 in 1-year-old infants. Overall, 17.8% of 321 specimens from 64.1% of 39 infants were polyomavirus positive. These data suggest that the gastrointestinal tract may be a site of polyomavirus persistence in humans.


Assuntos
Vírus BK/isolamento & purificação , Fezes/virologia , Vírus JC/isolamento & purificação , Infecções por Polyomavirus/diagnóstico , Vírus 40 dos Símios/isolamento & purificação , Eliminação de Partículas Virais , DNA Viral , Humanos , Lactente , Reação em Cadeia da Polimerase
16.
Cell Rep ; 14(12): 2912-24, 2016 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-26997279

RESUMO

Necrotizing enterocolitis (NEC) afflicts approximately 10% of extremely preterm infants with high fatality. Inappropriate bacterial colonization with Enterobacteriaceae is implicated, but no specific pathogen has been identified. We identify uropathogenic E. coli (UPEC) colonization as a significant risk factor for the development of NEC and subsequent mortality. We describe a large-scale deep shotgun metagenomic sequence analysis of the early intestinal microbiome of 144 preterm and 22 term infants. Using a pan-genomic approach to functionally subtype the E. coli, we identify genes associated with NEC and mortality that indicate colonization by UPEC. Metagenomic multilocus sequence typing analysis further defined NEC-associated strains as sequence types often associated with urinary tract infections, including ST69, ST73, ST95, ST127, ST131, and ST144. Although other factors associated with prematurity may also contribute, this report suggests a link between UPEC and NEC and indicates that further attention to these sequence types as potential causal agents is needed.


Assuntos
Enterocolite Necrosante/patologia , Escherichia coli Uropatogênica/genética , Antibacterianos/farmacologia , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Bacteriano/metabolismo , Farmacorresistência Bacteriana/efeitos dos fármacos , Enterocolite Necrosante/microbiologia , Enterocolite Necrosante/mortalidade , Fezes/microbiologia , Feminino , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Intestinos/microbiologia , Klebsiella/genética , Klebsiella/isolamento & purificação , Klebsiella/patogenicidade , Masculino , Metagenômica , Microbiota , Tipagem de Sequências Multilocus , Período Pós-Parto , Análise de Sequência de DNA , Taxa de Sobrevida , Escherichia coli Uropatogênica/isolamento & purificação , Escherichia coli Uropatogênica/patogenicidade
17.
Nat Methods ; 13(5): 435-8, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26999001

RESUMO

Identifying microbial strains and characterizing their functional potential is essential for pathogen discovery, epidemiology and population genomics. We present pangenome-based phylogenomic analysis (PanPhlAn; http://segatalab.cibio.unitn.it/tools/panphlan), a tool that uses metagenomic data to achieve strain-level microbial profiling resolution. PanPhlAn recognized outbreak strains, produced the largest strain-level population genomic study of human-associated bacteria and, in combination with metatranscriptomics, profiled the transcriptional activity of strains in complex communities.


Assuntos
Mucosa Intestinal/microbiologia , Metagenoma/genética , Metagenômica/métodos , Consórcios Microbianos/genética , Filogenia , Pele/microbiologia , Escherichia coli/classificação , Escherichia coli/genética , Escherichia coli/isolamento & purificação , Escherichia coli/patogenicidade , Perfilação da Expressão Gênica , Genoma Bacteriano , Alemanha , Humanos , Software , Especificidade da Espécie
18.
Biol Blood Marrow Transplant ; 22(3): 418-22, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26643031

RESUMO

The human gut microbiome is involved in vital biological functions, such as maintenance of immune homeostasis and modulation of intestinal development and enhanced metabolic capabilities. Disturbances of the intestinal microbiota have been associated with development and progression of inflammatory conditions, including graft-versus-host disease (GVHD). The fucosyltransferase 2 (FUT2) gene produces an enzyme that is responsible for the synthesis of the H antigen in body fluids and on the intestinal mucosa. FUT2 genotype has been shown to modify the gut microbiome. We hypothesized that FUT2 genotype influences risk of GVHD and bacterial translocation after allogeneic hematopoietic stem cell transplantation (HSCT). FUT2 genotype was determined in 150 consecutive patients receiving allogeneic HSCT at our center. We abstracted clinical characteristics and outcomes from the transplantation database. Cumulative risk of any acute GVHD varied by FUT2 genotype, with decreased risk in those with A/A genotype and increased risk in those with G/G genotype. In contrast, the cumulative incidence of bacteremia was increased in those with A/A genotype. We conclude that the FUT2 genotype influences risk of acute GVHD and bacteremia after HSCT. We hypothesize that the mechanisms involve altered intestinal surface glycosylation and microbial composition but this requires additional study.


Assuntos
Bacteriemia/genética , Fucosiltransferases/genética , Microbioma Gastrointestinal , Genótipo , Doença Enxerto-Hospedeiro/genética , Transplante de Células-Tronco Hematopoéticas , Adolescente , Adulto , Aloenxertos , Bacteriemia/enzimologia , Bacteriemia/etiologia , Translocação Bacteriana/genética , Criança , Pré-Escolar , Bases de Dados Factuais , Feminino , Doença Enxerto-Hospedeiro/enzimologia , Doença Enxerto-Hospedeiro/etiologia , Humanos , Lactente , Masculino , Fatores de Risco
19.
Am J Physiol Gastrointest Liver Physiol ; 310(6): G427-38, 2016 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-26702137

RESUMO

Intestinal resection resulting in short bowel syndrome (SBS) carries a heavy burden of long-term morbidity, mortality, and cost of care, which can be attenuated with strategies that improve intestinal adaptation. SBS infants fed human milk, compared with formula, have more rapid intestinal adaptation. We tested the hypothesis that the major noncaloric human milk oligosaccharide 2'-fucosyllactose (2'-FL) contributes to the adaptive response after intestinal resection. Using a previously described murine model of intestinal adaptation, we demonstrated increased weight gain from 21 to 56 days (P < 0.001) and crypt depth at 56 days (P < 0.0095) with 2'-FL supplementation after ileocecal resection. Furthermore, 2'-FL increased small bowel luminal content microbial alpha diversity following resection (P < 0.005) and stimulated a bloom in organisms of the genus Parabacteroides (log2-fold = 4.1, P = 0.035). Finally, transcriptional analysis of the intestine revealed enriched ontologies and pathways related to antimicrobial peptides, metabolism, and energy processing. We conclude that 2'-FL supplementation following ileocecal resection increases weight gain, energy availability through microbial community modulation, and histological changes consistent with improved adaptation.


Assuntos
Adaptação Fisiológica/efeitos dos fármacos , Intestinos/efeitos dos fármacos , Intestinos/cirurgia , Leite Humano/química , Síndrome do Intestino Curto/tratamento farmacológico , Trissacarídeos/farmacologia , Animais , Ceco/cirurgia , Dieta , Procedimentos Cirúrgicos do Sistema Digestório , Metabolismo Energético/efeitos dos fármacos , Humanos , Íleo/cirurgia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microbiota , RNA Ribossômico 16S/biossíntese , Trissacarídeos/química , Ganho de Peso/efeitos dos fármacos
20.
JAMA Pediatr ; 169(11): 1040-5, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26389824

RESUMO

IMPORTANCE: A genetic polymorphism affecting FUT2 secretor status in approximately one-quarter of humans of European descent affects the expression of histo-blood group antigens on the mucosal epithelia of human respiratory, genitourinary, and digestive tracts. These histo-blood group antigens serve as host receptor sites necessary for attachment and infection of some pathogens, including norovirus. OBJECTIVE: We investigated whether an association exists between FUT2 secretor status and laboratory-confirmed rotavirus infections in US children. DESIGN, SETTING, AND PARTICIPANTS: Multicenter case-control observational study involving active surveillance at 6 US pediatric medical institutions in the inpatient and emergency department clinical settings. We enrolled 1564 children younger than 5 years with acute gastroenteritis (diarrhea and/or vomiting) and 818 healthy controls frequency matched by age and month, from December 1, 2011, through March 31, 2013. MAIN OUTCOMES AND MEASURES: Paired fecal-saliva specimens were tested for rotavirus and for secretor status. Comparisons were made between rotavirus test-positive cases and healthy controls stratified by ethnicity and vaccination status. Adjusted multivariable analyses assessed the preventive association of secretor status against severe rotavirus gastroenteritis. RESULTS: One (0.5%) of 189 rotavirus test-positive cases was a nonsecretor, compared with 188 (23%) of 818 healthy control participants (P < .001). Healthy control participants of Hispanic ethnicity were significantly less likely to be nonsecretors (13%) compared with healthy children who were not of Hispanic ethnicity (25%) (P < .001). After controlling for vaccination and other factors, children with the nonsecretor FUT2 polymorphism appeared statistically protected (98% [95% CI, 84%-100%]) against severe rotavirus gastroenteritis. CONCLUSIONS AND RELEVANCE: Severe rotavirus gastroenteritis was virtually absent among US children who had a genetic polymorphism that inactivates FUT2 expression on the intestinal epithelium. We observed a strong epidemiologic association among children with rotavirus gastroenteritis compared with healthy control participants. The exact cellular mechanism behind this epidemiologic association remains unclear, but evidence suggests that it may be rotavirus genotype specific. The lower prevalence of nonsecretors among Hispanic children may translate to an enhanced burden of rotavirus gastroenteritis among this group. Our findings may have bearing on our full understanding of rotavirus infections and the effects of vaccination in diverse populations.


Assuntos
Fucosiltransferases/genética , Gastroenterite/epidemiologia , Infecções por Rotavirus/epidemiologia , Rotavirus/isolamento & purificação , Estudos de Casos e Controles , Pré-Escolar , Fezes/virologia , Feminino , Gastroenterite/genética , Gastroenterite/virologia , Predisposição Genética para Doença , Genótipo , Humanos , Lactente , Recém-Nascido , Masculino , Mutação , Estudos Prospectivos , Infecções por Rotavirus/genética , Infecções por Rotavirus/virologia , Saliva/virologia , Estados Unidos
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