RESUMO
The neonatal adaptive immune system, relatively naïve to foreign antigens, requires synergy with the innate immune system to protect the intestine...
Assuntos
Masculino , Feminino , Humanos , Aleitamento Materno , Intestino Delgado , Intestino Grosso , Leite Humano , Sistema Imunitário , Citocinas , QuimiocinasAssuntos
Humanos , Bactérias , Leite Humano , Oligossacarídeos , Intestino Delgado , Intestino GrossoRESUMO
OBJECTIVES: To determine the impact of empiric ampicillin and gentamicin use in the first week of life on microbial colonization and diversity in preterm infants. STUDY DESIGN: The 16s ribosomal DNA community profiling was used to compare the microbiota of 74 infants born ≤32 weeks gestational age by degree of antibiotic use in the first week of life. The degree of antibiotic use was classified as 0 days, 1-4 days, and 5-7 days of antibiotic administration. All of the antibiotic use was empiric, defined as treatment based solely on clinical suspicion of infection without a positive culture result. RESULTS: Infants who received 5-7 days of empiric antimicrobial agents in the first week had increased relative abundance of Enterobacter (P = .016) and lower bacterial diversity in the second and third weeks of life. Infants receiving early antibiotics also experienced more cases of necrotizing enterocolitis, sepsis, or death than those not exposed to antibiotics. CONCLUSIONS: Early empiric antibiotics have sustained effects on the intestinal microbiota of preterm infants. Intestinal dysbiosis in this population has been found to be associated with elevated risk of necrotizing enterocolitis, sepsis, or death.
Assuntos
Antibacterianos/uso terapêutico , Enterobacter/efeitos dos fármacos , Recém-Nascido Prematuro , Intestinos/microbiologia , Microbiota/efeitos dos fármacos , Ampicilina/efeitos adversos , Ampicilina/uso terapêutico , Antibacterianos/efeitos adversos , Biodiversidade , Estudos de Coortes , Impressões Digitais de DNA , DNA Ribossômico/genética , Feminino , Gentamicinas/efeitos adversos , Gentamicinas/uso terapêutico , Idade Gestacional , Humanos , Recém-Nascido , Estudos Longitudinais , Masculino , Ohio , RNA Ribossômico 16S/genéticaRESUMO
OBJECTIVE: To investigate secretor gene fucosyltransferase 2 (FUT2) polymorphism and secretor phenotype in relation to outcomes of prematurity. STUDY DESIGN: Study infants were ≤32 weeks gestational age. Secretor genotype was determined from salivary DNA. Secretor phenotype was measured with H antigen, the carbohydrate produced by secretor gene enzymes, in saliva samples collected on day 9 ± 5. The optimal predictive cutoff point in salivary H values was identified with Classification and Regression Tree analysis. Study outcomes were death, necrotizing enterocolitis (NEC, Bell's stage II/III), and confirmed sepsis. RESULTS: There were 410 study infants, 26 deaths, 30 cases of NEC, and 96 cases of sepsis. Analyzed by genotype, 13% of 95 infants who were non-secretors, 5% of 203 infants who were heterozygotes, and 2% of 96 infants who were secretor dominant died (P = .01). Analyzed by phenotype, 15% of 135 infants with low secretor phenotype died, compared with 2% of 248 infants with high secretor phenotype (predictive value = 76%, P < .001). Low secretor phenotype was associated (P < .05) with NEC, and non-secretor genotype was associated (P = .05) with gram negative sepsis. Secretor status remained significant after controlling for multiple clinical factors. CONCLUSIONS: Secretor genotype and phenotype may provide strong predictive biomarkers of adverse outcomes in premature infants.
Assuntos
DNA/genética , Fucosiltransferases/genética , Recém-Nascido Prematuro , Polimorfismo Genético , Causas de Morte/tendências , Enterocolite Necrosante/enzimologia , Enterocolite Necrosante/genética , Enterocolite Necrosante/mortalidade , Seguimentos , Fucosiltransferases/metabolismo , Genótipo , Humanos , Mortalidade Infantil/tendências , Recém-Nascido , Ohio/epidemiologia , Prognóstico , Estudos Retrospectivos , Saliva/enzimologia , Galactosídeo 2-alfa-L-FucosiltransferaseRESUMO
Adiponectin is a protein hormone produced by adipose tissue, whose circulating levels are inversely related to adiposity and inflammation. Adiponectin circulates as oligomers, from the low-molecular-weight trimer to the high-molecular-weight octodecamer (18 mer). Each oligomer has distinct biological activities, which include enhancement of insulin sensitivity and metabolic control and suppression of inflammation. Adiponectin occurs in human milk at higher concentrations than leptin. The adiponectin in human milk is almost entirely of the high-molecular-weight form, the form with the highest activity in controlling many types of metabolic processes. Human adiponectin fed to infant mice is transported across the intestinal mucosa into the serum. An inverse relationship between adiponectin levels in milk and adiposity (weight-for-height) of the breast-fed infant was observed and could be due to modulation of infant metabolism by milk adiponectin and may be related to the observed protection against obesity by breast-feeding. Human milk may be a medium whereby the hormonal milieu (in response to internal factors and the environment) of the mother can be used to communicate with the breast-fed infant to modify infant metabolic processes. Transmission of information from mother to infant through milk may allow adaptation to fluctuating environmental conditions.
Assuntos
Leite Humano/química , Adiponectina/análise , Adiponectina/fisiologia , Adiposidade/fisiologia , Peso Corporal , Desenvolvimento Infantil/fisiologia , Feminino , Humanos , LactenteRESUMO
BACKGROUND: Adiponectin, a circulating adipocyte protein, is associated with lower obesity. We have previously shown that adiponectin is present in human milk. This study determined whether higher milk adiponectin is associated with infant growth and investigated milk adiponectin's oligomeric form. DESIGN AND METHODS: This is a study of two parallel longitudinal cohorts of breastfed infants born between 1998 and 2005. Forty-five mother-infant pairs from Cincinnati, OH and 277 mother-infant pairs from Mexico City, Mexico were analyzed. All participants were healthy, term infants breastfed at least 1 month who completed 6 months of follow-up. Monthly milk samples (n = 1,379) up to 6 months were assayed for adiponectin by radioimmunoassay. Infant weight-for-age, length-for-age, and weight-for-length Z-scores up to 6 months of age were calculated using World Health Organization standards. Repeated-measures analysis was conducted. The structural form of human milk adiponectin was assessed by western blot. RESULTS: In the population studies, initial milk adiponectin was 24.0 +/- 8.6 microg/L and did not differ by cohort. Over the first 6 months, higher milk adiponectin was associated with lower infant weight-for-age Z-score (-0.20 +/- 0.04, p < 0.0001) and weight-for-length Z-score (-0.29 +/- 0.08, p = 0.0002) but not length-for-age Z-score, adjusted for covariates, with no difference by cohort. By western blot, human milk adiponectin was predominantly in the biologically active high-molecular-weight form. CONCLUSIONS: Our data suggest milk adiponectin may play a role in the early growth and development of breastfed infants.
Assuntos
Adiponectina/análise , Crescimento , Recém-Nascido/crescimento & desenvolvimento , Leite Humano/química , Adiponectina/química , Adulto , Fatores Etários , Estatura/fisiologia , Peso Corporal/fisiologia , Estudos de Coortes , Feminino , Humanos , Lactente , Estudos Longitudinais , Masculino , México , Peso Molecular , Obesidade/epidemiologia , Obesidade/etiologia , Obesidade/prevenção & controle , Ohio , RadioimunoensaioRESUMO
Noroviruses (NVs) recognize human histo-blood group antigens (HBGAs) as receptors. We characterized the interaction of human milk samples with recombinant virus-like particles representing VA387, Norwalk, VA207, and MOH. Milk samples from 60 healthy women were tested for human HBGAs and for their ability to block the binding of NVs. Fifty-four women were secretors (Se+), and 6 were nonsecretors (Se-). No women had detectable A or B antigens in their milk samples. All 54 Se+ milk samples, but 0 of 6 Se- milk samples, blocked VA387 and Norwalk virus (Se+ binders) from binding to saliva samples. All 6 Lewis-positive Se- milk samples blocked binding to VA207, and variable blocking activities were exhibited by the Se+ milk samples. No milk samples blocked the binding of MOH to A and B antigens. Secretor and Lewis, but not A or B antigens, were present in human milk and were responsible for blocking NV binding to receptors and therefore are likely to be decoy receptors that protect breast-fed infants from NV infection.
Assuntos
Antígenos de Grupos Sanguíneos/metabolismo , Leite Humano/imunologia , Norovirus/fisiologia , Receptores Virais/metabolismo , Saliva/imunologia , Infecções por Caliciviridae/prevenção & controle , Feminino , Humanos , México , Saliva/virologia , Virginia , Inativação de VírusRESUMO
OBJECTIVE: To determine the association between maternal milk levels of 2-linked fucosylated oligosaccharide and prevention of diarrhea as a result of Campylobacter, caliciviruses, and diarrhea of all causes in breast-fed infants. STUDY DESIGN: Data and banked samples were analyzed from 93 breast-feeding mother-infant pairs who were prospectively studied during 1988-1991 from birth to 2 years with infant feeding and diarrhea data collected weekly; diarrhea was diagnosed by a study physician. Milk samples obtained 1 to 5 weeks postpartum were analyzed for oligosaccharide content. Data were analyzed by Poisson regression. RESULTS: Total 2-linked fucosyloligosaccharide in maternal milk ranged from 0.8 to 20.8 mmol/L (50%-92% of milk oligosaccharide). Moderate-to-severe diarrhea of all causes (n=77 cases) occurred less often (P=.001) in infants whose milk contained high levels of total 2-linked fucosyloligosaccharide as a percent of milk oligosaccharide. Campylobacter diarrhea (n=31 cases) occurred less often (P=.004) in infants whose mother's milk contained high levels of 2'-FL, a specific 2-linked fucosyloligosaccharide, and calicivirus diarrhea (n=16 cases) occurred less often (P=.012) in infants whose mother's milk contained high levels of lacto-N-difucohexaose (LDFH-I), another 2-linked fucosyloligosaccharide. CONCLUSION: This study provides novel evidence suggesting that human milk oligosaccharides are clinically relevant to protection against infant diarrhea.
Assuntos
Aleitamento Materno , Infecções por Campylobacter/prevenção & controle , Diarreia Infantil/prevenção & controle , Leite Humano/química , Oligossacarídeos/uso terapêutico , Adolescente , Adulto , Coleta de Dados , Diarreia Infantil/classificação , Diarreia Infantil/microbiologia , Escolaridade , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Idade Materna , Oligossacarídeos/metabolismo , Distribuição de Poisson , Estudos Prospectivos , Índice de Gravidade de DoençaRESUMO
The most common cause of infant mortality is diarrhea; the most common cause of bacterial diarrhea is Campylobacter jejuni, which is also the primary cause of motor neuron paralysis. The first step in campylobacter pathogenesis is adherence to intestinal mucosa. We found that such binding was inhibited in vitro by human milk and, with high avidity, by alpha1,2-fucosylated carbohydrate moieties containing the H(O) blood group epitope (Fuc alpha 1,2Gal beta 1,4GlcNAc em leader ). In studies on the mechanism of adherence, campylobacter, which normally does not bind to Chinese hamster ovary cells, bound avidly when the cells were transfected with a human alpha1,2-fucosyltransferase gene that caused overexpression of H-2 antigen; binding was specifically inhibited by H-2 ligands (lectins Ulex europaeus and Lotus tetragonolobus and H-2 monoclonal antibody), H-2 mimetics, and human milk oligosaccharides. Human milk oligosaccharides inhibited campylobacter colonization of mice in vivo and human intestinal mucosa ex vivo. Campylobacter colonization of nursing mouse pups was inhibited if their dams had been transfected with a human alpha1,2-fucosyltransferase gene that caused expression of H(O) antigen in milk. We conclude that campylobacter binding to intestinal H-2 antigen is essential for infection. Milk fucosyloligosaccharides and specific fucosyl alpha1,2-linked molecules inhibit this binding and may represent a novel class of antimicrobial agents.