RESUMO
Importance: Establishment of the infant microbiome has lifelong implications on health and immunity. Gut microbiota of breastfed compared with nonbreastfed individuals differ during infancy as well as into adulthood. Breast milk contains a diverse population of bacteria, but little is known about the vertical transfer of bacteria from mother to infant by breastfeeding. Objective: To determine the association between the maternal breast milk and areolar skin and infant gut bacterial communities. Design, Setting, and Participants: In a prospective, longitudinal study, bacterial composition was identified with sequencing of the 16S ribosomal RNA gene in breast milk, areolar skin, and infant stool samples of 107 healthy mother-infant pairs. The study was conducted in Los Angeles, California, and St Petersburg, Florida, between January 1, 2010, and February 28, 2015. Exposures: Amount and duration of daily breastfeeding and timing of solid food introduction. Main Outcomes and Measures: Bacterial composition in maternal breast milk, areolar skin, and infant stool by sequencing of the 16S ribosomal RNA gene. Results: In the 107 healthy mother and infant pairs (median age at the time of specimen collection, 40 days; range, 1-331 days), 52 (43.0%) of the infants were male. Bacterial communities were distinct in milk, areolar skin, and stool, differing in both composition and diversity. The infant gut microbial communities were more closely related to an infant's mother's milk and skin compared with a random mother (mean difference in Bray-Curtis distances, 0.012 and 0.014, respectively; P < .001 for both). Source tracking analysis was used to estimate the contribution of the breast milk and areolar skin microbiomes to the infant gut microbiome. During the first 30 days of life, infants who breastfed to obtain 75% or more of their daily milk intake received a mean (SD) of 27.7% (15.2%) of the bacteria from breast milk and 10.3% (6.0%) from areolar skin. Bacterial diversity (Faith phylogenetic diversity, P = .003) and composition changes were associated with the proportion of daily breast milk intake in a dose-dependent manner, even after the introduction of solid foods. Conclusions and Relevance: The results of this study indicate that bacteria in mother's breast milk seed the infant gut, underscoring the importance of breastfeeding in the development of the infant gut microbiome.
Assuntos
Fezes/microbiologia , Microbioma Gastrointestinal , Leite Humano/microbiologia , Mamilos/microbiologia , Aleitamento Materno , Feminino , Humanos , Lactente , Recém-Nascido , Estudos Longitudinais , Masculino , Mães , Filogenia , Estudos Prospectivos , Análise de Sequência de RNA/métodosRESUMO
More than 1 million HIV-exposed, uninfected infants are born annually to HIV-positive mothers worldwide. This growing population of infants experiences twice the mortality of HIV-unexposed infants. We found that although there were very few differences seen in the microbiomes of mothers with and without HIV infection, maternal HIV infection was associated with changes in the microbiome of HIV-exposed, uninfected infants. Furthermore, we observed that human breast milk oligosaccharides were associated with bacterial species in the infant microbiome. The disruption of the infant's microbiome associated with maternal HIV infection may contribute to the increased morbidity and mortality of HIV-exposed, uninfected infants.
Assuntos
Infecções por HIV/transmissão , Microbiota/fisiologia , Aleitamento Materno , Estudos Transversais , Feminino , Infecções por HIV/microbiologia , Humanos , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas , Leite Humano/química , Mães , Oligossacarídeos/metabolismo , Gravidez , Complicações Infecciosas na Gravidez/microbiologia , Estudos Prospectivos , Fatores de RiscoRESUMO
Accumulating evidence suggests that rates of low bone mass are greater in HIV-infected males than females. Of 11 biomarkers assessed by sex and HIV-status, HIV-infected males had increased levels of soluble CD14 which inversely correlated with bone mineral content and bone mineral density measures, suggesting macrophage activation as a possible mechanism of differential bone loss.
Assuntos
Terapia Antirretroviral de Alta Atividade , Densidade Óssea/efeitos dos fármacos , Doenças Ósseas Metabólicas/fisiopatologia , Infecções por HIV/fisiopatologia , Ativação de Macrófagos , Osteoporose/fisiopatologia , Coluna Vertebral/patologia , Absorciometria de Fóton , Adolescente , Adulto , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Doenças Ósseas Metabólicas/diagnóstico por imagem , Doenças Ósseas Metabólicas/virologia , Estudos Transversais , Feminino , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Osteoporose/diagnóstico por imagem , Osteoporose/virologia , Porto Rico/epidemiologia , Fatores Sexuais , Estados Unidos/epidemiologia , Adulto JovemRESUMO
Circulating levels of microbial products such as lipopolysaccharide (LPS) are increased in HIV infection. Microbial translocation promotes obesity, insulin resistance, and dyslipidemia in other settings. We examined data from 178 subjects: an Indiana University (IU) cross-sectional study [N=49 on antiretroviral therapy (ART), N=47 not on ART], and a 24 week prospective study of ART initiation ACTG 5152s (N=82). Pearson correlations were used to describe relationships of plasma LPS levels and soluble CD14 (sCD14), a marker of monocyte activation, with metabolic and body composition measures. HOMA-IR (a measure of insulin resistance) and LPS were correlated for the combined cohorts (r=0.19, p=0.02), particularly in the 5152s ART-naive cohort (r=0.41, p<0.01). Triglycerides were correlated with LPS in the combined cohort (r=0.32, p<0.01), and all subsets excluding the IU on ART subset. There were negative correlations between sCD14 and high-density lipoprotein (HDL) cholesterol in all subjects (r=-0.21, p<0.01), as well as the IU subset not on ART (r=-0.32, p=0.04). Large particle HDL as measured by NMR spectroscopy, but not HDL cholesterol, was negatively correlated with LPS (r=-0.18, p=0.02), particularly among the IU subset receiving ART (r=-0.33, p=0.03). In the combined cohorts, sCD14 was negatively correlated with lean mass as well as trunk and limb fat. There is a relationship between microbial translocation markers and metabolic effects, particularly lipoproteins. During prolonged ART, microbial translocation was associated with an adverse effect on large HDL and thus may contribute to the increased cardiovascular disease risk observed during chronic treatment of HIV.
Assuntos
Antirretrovirais/uso terapêutico , Translocação Bacteriana , Composição Corporal , Infecções por HIV/tratamento farmacológico , Infecções por HIV/patologia , Metaboloma , Adulto , Estudos Transversais , Feminino , Hospitais Universitários , Humanos , Indiana , Receptores de Lipopolissacarídeos/sangue , Lipopolissacarídeos/sangue , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Circulating levels of microbial products are increased in HIV infection, and provoke endothelial dysfunction in other disease settings. METHODOLOGY/PRINCIPAL FINDINGS: We examined data from a cross-sectional single site study at Indiana University (Indiana, Nâ=â85) and a 24- week multicenter prospective study of antiretroviral therapy (ART) initiation (ACTG 5152s, Nâ=â75). Brachial artery flow-mediated dilation (FMD) was measured by ultrasound. Plasma lipopolysaccharide (LPS) and soluble CD14 (sCD14) levels were measured from stored specimens and correlated with FMD values using Pearson correlations. The Indiana subjects were 63% male with a mean age of 39 years and a median CD4 count of 406 cells/mm(3) (388 not on ART, 464 on ART). The 5152s subjects were 92% were male with a mean age of 35 years and a median CD4 count of 251 cells/mm(3) at entry which increased to 396 cells/mm(3) on ART. When analyzing the two cohorts individually or in combination neither sCD14 nor LPS correlated significantly with FMD. In a pre-specified subgroup analysis of the Indiana subjects receiving ART (Nâ=â46, mean ART duration 40 months) LPS was inversely correlated with FMD (râ=â-0.33, pâ=â0.02), but not sCD14 (râ=â-0.01, pâ=â0.9). Multivariate analysis confirmed LPS as an independent predictor of FMD in this subgroup (pâ=â0.02). CONCLUSIONS/SIGNIFICANCE: In HIV-infected individuals on prolonged ART, higher LPS levels are associated with worse endothelial function but not in untreated subjects or at 24 weeks after ART initiation. Persistent microbial translocation may contribute to arterial dysfunction and the increased cardiovascular disease risk observed in individuals on long-term ART.
Assuntos
Endotélio/fisiopatologia , Infecções por HIV/complicações , Infecções por HIV/fisiopatologia , Adulto , Antirretrovirais/uso terapêutico , Transporte Biológico , Artéria Braquial/fisiopatologia , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/etiologia , Estudos de Coortes , Estudos Transversais , Endotélio/microbiologia , Endotélio/virologia , Feminino , Infecções por HIV/microbiologia , Humanos , Indiana , Receptores de Lipopolissacarídeos/biossíntese , Lipopolissacarídeos/sangue , Lipopolissacarídeos/metabolismo , Masculino , Análise Multivariada , Estudos Prospectivos , Ultrassonografia/métodosRESUMO
Telomere capping is the essential function of telomeres. To identify new genes involved in telomere capping, we carried out a genome-wide screen in Saccharomyces cerevisiae for suppressors of cdc13-1, an allele of the telomere-capping protein Cdc13. We report the identification of five novel suppressors, including the previously uncharacterized gene YML036W, which we name CGI121. Cgi121 is part of a conserved protein complex -- the KEOPS complex -- containing the protein kinase Bud32, the putative peptidase Kae1, and the uncharacterized protein Gon7. Deletion of CGI121 suppresses cdc13-1 via the dramatic reduction in ssDNA levels that accumulate in cdc13-1 cgi121 mutants. Deletion of BUD32 or other KEOPS components leads to short telomeres and a failure to add telomeres de novo to DNA double-strand breaks. Our results therefore indicate that the KEOPS complex promotes both telomere uncapping and telomere elongation.