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BACKGROUND: Alongside microbiota development, the evolution of the resistome is crucial in understanding the early-life acquisition and persistence of Antibiotic Resistance Genes (ARGs). Therefore, the aim of this study is to provide a comprehensive view of the evolution and dynamics of the neonatal resistome from 7 days to 4 months of age using a high-throughput qPCR platform. METHODS: In the initial phase, a massive screening of 384 ARGs using a high-throughput qPCR in pooled healthy mother-infant pairs feces from the MAMI cohort was carried out to identify the most abundant and prevalent ARGs in infants and in mothers. This pre-analysis allowed for later targeted profiling in a large number of infants in a longitudinal manner during the first 4 months of life. 16S rRNA V3-V4 amplicon sequencing was performed to asses microbial composition longitudinally. Potential factors influencing the microbiota and ARGs in this period were also considered, such as mode of birth and breastfeeding type. RESULTS: Following the massive screening, the top 45 abundant ARGs and mobile genetic elements were identified and studied in 72 infants during their first months of life (7 days, 1, 2, and 4 months). These genes were associated with resistance to aminoglycosides, beta-lactams and tetracyclines, among others, as well as integrons, and other mobile genetic elements. Changes in both ARG composition and quantity were observed during the first 4 months of life: most ARGs abundance increased over time, but mobile genetic elements decreased significantly. Further exploration of modulating factors highlighted the effect on ARG composition of specific microbial genus, and the impact of mode of birth at 7 days and 4 months. The influence of infant formula feeding was observed at 4-month-old infants, who exhibited a distinctive resistome composition. CONCLUSIONS: This study illustrates the ARG evolution and dynamics in the infant gut by use of a targeted, high-throughput, quantitative PCR-based method. An increase in antibiotic resistance over the first months of life were observed with a fundamental role of delivery mode in shaping resistance profiles. Further, we highlighted the influence of feeding methods on the resistome development. These findings offer pivotal insights into dynamics of and factors influencing early-life resistome, with potential avenues for intervention strategies.
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Antibacterianos , Fezes , Microbioma Gastrointestinal , RNA Ribossômico 16S , Humanos , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/genética , Lactente , Recém-Nascido , Fezes/microbiologia , Feminino , Antibacterianos/farmacologia , RNA Ribossômico 16S/genética , Masculino , Aleitamento Materno , Bactérias/genética , Bactérias/efeitos dos fármacos , Bactérias/classificação , Genes Bacterianos/genética , Farmacorresistência Bacteriana/genética , Evolução Molecular , Resistência Microbiana a Medicamentos/genética , Estudos LongitudinaisRESUMO
BACKGROUND: Animal and human studies indicate that exposure to air pollution and natural environments might modulate the gut microbiota, but epidemiological evidence is very scarce. OBJECTIVES: To assess the potential impact of pre- and postnatal exposure to air pollution and green spaces on infant gut microbiota assembly and trajectories during the first year of life. METHODS: MAMI ("MAternal MIcrobes") birth cohort (Valencia, Spain, N = 162) was used to study the impact of environmental exposure (acute and chronic) on infant gut microbiota during the first year of life (amplicon-based 16S rRNA sequencing). At 7 days and at 1, 6 and 12 months, residential pre- and postnatal exposure to air pollutants (NO2, black carbon -BC-, PM2.5 and O3) and green spaces indicators (NDVI and area of green spaces at 300, 500 and 1000 m buffers) were obtained. For the association between exposures and alpha diversity indicators linear regression models (cross-sectional analyses) and mixed models, including individual as a random effect (longitudinal analyses), were applied. For the differential taxon analysis, the ANCOM-BC package with a log count transformation and multiple-testing corrections were used. RESULTS: Acute exposure in the first week of life and chronic postnatal exposure to NO2 were associated with a reduction in microbial alpha diversity, while the effects of green space exposure were not evident. Acute and chronic (prenatal or postnatal) exposure to NO2 resulted in increased abundance of Haemophilus, Akkermansia, Alistipes, Eggerthella, and Tyzerella populations, while increasing green space exposure associated with increased Negativicoccus, Senegalimassilia and Anaerococcus and decreased Tyzzerella and Lachnoclostridium populations. DISCUSSION: We observed a decrease in the diversity of the gut microbiota and signs of alteration in its composition among infants exposed to higher levels of NO2. Increasing green space exposure was also associated with changes in gut microbial composition. Further research is needed to confirm these findings.
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Poluição do Ar , Microbioma Gastrointestinal , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Feminino , Lactente , Espanha , Poluição do Ar/efeitos adversos , Recém-Nascido , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/toxicidade , Coorte de Nascimento , Masculino , Exposição Ambiental/efeitos adversos , Gravidez , Estudos de Coortes , Exposição Materna/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal/microbiologiaRESUMO
OBJECTIVE: Consensus around the ideal chart to classify preterm babies is scant. It is particularly relevant in small for gestational age (SGA) infants due to its clinical and therapeutic implications. The aim of the study was to compare Olsen, Intergrowth-21st, and Fenton growth charts, regarding the classification at birth and incidence of SGA preterm infants. STUDY DESIGN: Retrospective study of 529 preterm infants ≤ 32 weeks of gestational age. Birth weight Z-score was calculated applying the three growth charts and ponderal index (PI) was also estimated. Incidence of SGA (birth weight < 10th percentile) and clinical outcome were compared according to the chart used. RESULTS: Incidence of SGA was significantly higher (p < 0.001) with Olsen (101 cases, 19.1%) compared with Intergrowth-21st (75 cases, 14.2%) and Fenton (53 cases, 10%). Differences were also found with PI of SGA preterm infants, as those infants classified by Olsen were mostly symmetric (PI > 10th percentile), while Fenton and Intergrowth-21st identified less symmetric SGA infants. Kappa concordance between Intergrowth-21st and Fenton was 0.805, Intergrowth-21st versus Olsen 0.824, and Fenton versus Olsen 0.641. No differences were observed on neonatal morbidities or mortality. CONCLUSION: Significant differences were detected when classifying very preterm infants at birth according to the growth chart, mainly among symmetric SGA. Concordance between Fenton and Olsen was poor, but Intergrowth-21st showed high concordance with Fenton and Olsen. However, further research is needed to select the ideal chart. Variability in the population selected to create the curves and the accuracy dating the pregnancy are factors that may have explained differences. KEY POINTS: · Very preterm infants are differently classified at birth with various growth charts.. · Higher incidence of small for gestational age infants with Olsen compared with Fenton or Intergrowth.. · Variability in population selection and accuracy in dating pregnancy may have explained differences..
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PURPOSE: Human milk (HM) composition is influenced by factors, like maternal diet and body stores, among other factors. For evaluating the influence of maternal fatty acid (FA) status on milk FA composition, the correlation between FA content in HM and in maternal plasma, erythrocytes, and adipose tissue was investigated. METHODS: 223 European women who delivered at term, provided HM samples over first four months of lactation. Venous blood and adipose tissue (only from mothers who consented and underwent a C-section delivery) were sampled at delivery. FAs were assessed in plasma, erythrocytes, adipose tissue, and HM. Evolution of HM FAs over lactation and correlations between FA content in milk and tissues and between mother's blood and cord blood were established. RESULTS: During lactation, arachidonic acid (ARA) and docosahexaenoic acid (DHA) significantly decreased, while linoleic acid (LA), alpha-linolenic acid (ALA), and eicosapentaenoic acid (EPA) remained stable. Positive correlations were observed between HM and adipose tissue for palmitic, stearic, oleic, and polyunsaturated fatty acids (PUFAs). Correlations were found between milk and plasma for oleic, LA, ARA, ALA, DHA, monounsaturated fatty acids (MUFAs), and PUFAs. No correlation was observed between erythrocytes and HM FAs. LA and ALA were more concentrated in maternal blood than in infant blood, contrary to ARA and DHA, supporting that biomagnification of LCPUFAs may have occurred during pregnancy. CONCLUSIONS: These data show that maternal adipose tissue rather than erythrocytes may serve as reservoir of PUFAs and LCPUFAs for human milk. Plasma also supplies PUFAs and LCPUFAs to maternal milk. If both, adipose tissue and plasma PUFAs, are reflection of dietary intake, it is necessary to provide PUFAs and LCPUFAs during pregnancy or even before conception and lactation to ensure availability for mothers and enough supply for the infant via HM.
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Ácidos Graxos , Leite Humano , Tecido Adiposo , Ácido Araquidônico , Aleitamento Materno , Ácidos Docosa-Hexaenoicos , Ácidos Graxos Insaturados , Feminino , Humanos , Lactente , Lactação , Ácido Linoleico , GravidezRESUMO
OBJECTIVES: Over the last several decades, there has been a tendency towards a predominance of less symptomatic forms of coeliac disease (CD) and an increase in the patient age at diagnosis. This study aimed to assess the clinical presentation and diagnostic process of paediatric CD in Spain. METHODS: A nationwide prospective, observational, multicentre registry of new paediatric CD cases was conducted from January 2011 to June 2017. The data regarding demographic variables, type of birth, breast-feeding history, family history of CD, symptoms, height and weight, associated conditions, serological markers, human leukocyte antigen (HLA) phenotype, and histopathological findings were collected. RESULTS: In total, 4838 cases (61% girls) from 73 centres were registered. The median age at diagnosis was 4âyears. Gastrointestinal symptoms were detected in 71.4% of the patients, and diarrhoea was the most frequent symptom (45.9%). The most common clinical presentation was the classical form (65.1%) whereas 9.8% ofthe patients were asymptomatic. There was a trend towards an increase in the age at diagnosis, proportion of asymptomatic CD cases, and usage of anti-deamidated gliadin peptide antibodies and HLA typing for CD diagnosis. There was, however, a decreasing trend in the proportion of patients undergoing biopsies. Some of these significant trend changes may reflect the effects of the 2012 ESPGHAN diagnosis guidelines. CONCLUSIONS: Paediatric CD in Spain is evolving in the same direction as in the rest of Europe, although classical CD remains the most common presentation form, and the age at diagnosis remains relatively low.
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Doença Celíaca , Sistema de Registros , Anticorpos , Doença Celíaca/complicações , Doença Celíaca/diagnóstico , Doença Celíaca/epidemiologia , Criança , Feminino , Gliadina , Humanos , Masculino , Estudos Prospectivos , Espanha/epidemiologiaRESUMO
We evaluated the Panbio™ COVID-19 Ag Rapid Test Device as a point-of-care diagnostic tool for COVID-19 in 357 patients at a pediatric emergency department. Thirty-four patients tested positive by reverse transcription polymerase chain reaction, of which 24 were positive by the antigen assay. The sensitivity and specificity of the assay were 70.5% and 100%, respectively.
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Antígenos Virais/imunologia , COVID-19/diagnóstico , COVID-19/imunologia , SARS-CoV-2/imunologia , Teste de Ácido Nucleico para COVID-19/métodos , Teste Sorológico para COVID-19/métodos , Criança , Pré-Escolar , Serviço Hospitalar de Emergência , Feminino , Humanos , Testes Imunológicos/métodos , Lactente , Masculino , Nasofaringe/imunologia , Nasofaringe/virologia , Testes Imediatos , Estudos Prospectivos , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Breast milk is a complex biofluid that provides nutrients and bioactive agents, including bacteria, for the development of the infant gut microbiota. However, the impact of maternal diet and other factors, such as mode of delivery and antibiotic exposure, on the breast milk microbiota has yet to be understood. OBJECTIVES: This study aimed to examine the association between maternal diet and breast milk microbiota and to ascertain the potential role of mode of delivery and antibiotic exposure. METHODS: In a cross-sectional study of the MAMI cohort, breast milk microbiota profiling was assessed in 120 samples from healthy mothers by 16S rRNA gene sequencing. Maternal dietary information was recorded through an FFQ, and clinical characteristics, including mode of delivery, antibiotic exposure, and exclusive breastfeeding, were collected. RESULTS: Maternal diet was grouped into 2 clusters: Cluster I (high intake of plant protein, fiber, and carbohydrates), and Cluster II (high intake of animal protein and lipids). Breast milk microbiota was shaped by maternal dietary clusters. Staphylococcus and Bifidobacterium were associated with carbohydrate intake whereas the Streptococcus genus was associated with intakes of the n-3 PUFAs [EPA and docosapentaenoic acid (22:5ω-3)]. Mode of delivery and antibiotic exposure influenced breast milk microbiota in a diet cluster-dependent manner. Differences between/among the maternal dietary clusters were found in the milk microbiota of the cesarean-section (C-section)/antibiotic group, whereas no differences were observed in vaginal births. Lower abundances of Lactobacillus, Bacteroides, and Sediminibacterium genera were observed in Cluster II/C-section/antibiotic exposure compared with the other groups. CONCLUSIONS: Maternal diet shapes the composition and diversity of breast milk microbiota, with the most important contributions coming from dietary fiber and both plant and animal protein intakes. The relation between the maternal diet and the milk microbiota needs further research because it has a key impact on infant microbiota development and contributes to infant health outcomes in the short and long term.This trial was registered at clinicaltrials.gov as NCT03552939.
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Antibacterianos/administração & dosagem , Bactérias/classificação , Dieta , Microbiota/efeitos dos fármacos , Leite Humano/química , Leite Humano/microbiologia , Adulto , Bactérias/efeitos dos fármacos , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Lactente , Recém-Nascido , MasculinoRESUMO
BACKGROUND: The relationship between human milk oligosaccharides (HMOs) and infant growth and adiposity is not fully understood and comprehensive studies are missing from the current literature. METHODS: We screened and recruited 370 healthy, pregnant women and their infants from seven European countries. Breastmilk samples were collected using standardized procedures at six time points over 4 months, as were infant parameters. Correlations and associations between HMO area under the curve, anthropometric data, and fat mass at 4 months were tested. RESULTS: Lacto-N-neotetraose had a negative correlation with the change in length (rs = -0.18, P = 0.02). Sialyllacto-N-tetraose c (LSTc) had a positive correlation with weight for length (rs = 0.19, P = 0.015). Infants at the 25th upper percentile were fed milk higher in 3'-sialyllactose and LSTc (P = 0.017 and P = 0.006, respectively) compared to the lower 25th percentile of the weight-for-length z-score gain over 4 months of lactation. No significant associations between growth and body composition and Lewis or secretor-dependent HMOs like 2'-fucosyllactose were identified. CONCLUSIONS: Changes in the HMO composition of breastmilk during the first 4 months appear to have little influence on infant growth and body composition in this cohort of healthy mothers and infants. IMPACT: Modest associations exist between individual HMO and infant growth outcomes at least in healthy growing populations. Our study provides a comprehensive investigation of associations between all major HMO and infant growth and adiposity including several time points. Certain groups of HMOs, like the sialylated, may be associated with adiposity during the first months of lactation. HMO may modulate the risk of future metabolic disease. Future population studies need to address the role of specific groups of HMOs in the context of health and disease to understand the long-term impact.
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Adiposidade , Crescimento , Lactação , Leite Humano/química , Oligossacarídeos/química , Adolescente , Adulto , Composição Corporal , Estudos de Coortes , Feminino , Humanos , Lactente , Masculino , Adulto JovemRESUMO
According to the developmental origins of health and disease hypothesis, our health is determined by events experienced in utero and during early infancy. Indeed, both our prenatal and postnatal nutrition conditions have an impact on the initial architecture and activity of our microbiota. Recent evidence has underlined the importance of the composition of the early gut microbiota in relation to malnutrition, whether it be undernutrition or overnutrition, that is, in terms of both stunted and overweight development. It remains unclear how early microbial contact is linked to the risk of disease, as well as whether alterations in the microbiome underlie the pathogenesis of malnutrition or are merely the end result of it, which indicates that thequestion of causality must urgently be answered. This review provides information on the complex interaction between the microbiota and nutrition during the first 1,000 days of life, taking into account the impact of both undernutrition and overnutrition on the microbiota and on infants' health outcomes in the short- and long-term.
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Microbioma Gastrointestinal , Transtornos da Nutrição do Lactente , Feminino , Humanos , Lactente , Fenômenos Fisiológicos da Nutrição do Lactente , Recém-Nascido , Gravidez , Fenômenos Fisiológicos da Nutrição Pré-NatalRESUMO
BACKGROUND AND OBJECTIVES: Breast milk contains several bioactive factors including human milk oligosaccharides (HMOs) and microbes that shape the infant gut microbiota. HMO profile is determined by secretor status; however, their influence on milk microbiota is still uncovered. This study is aimed to determine the impact of the FUT2 genotype on the milk microbiota during the first month of lactation and the association with HMO. METHODS: Milk microbiota from 25 healthy lactating women was determined by quantitative polymerase chain reaction and 16S gene pyrosequencing. Secretor genotype was obtained by polymerase chain reaction-random fragment length polymorphisms and by HMO identification and quantification. RESULTS: The most abundant bacteria were Staphylococcus and Streptococcus, followed by Enterobacteriaceae-related bacteria. The predominant HMO in secretor milk samples were 2'FL and lacto-N-fucopentaose I, whereas non-secretor milk was characterized by lacto-N-fucopentaose II and lacto-N-difucohexaose II. Differences in microbiota composition and quantity were found depending on secretor/non-secretor status. Lactobacillus spp, Enterococcus spp, and Streptococcus spp were lower in non-secretor than in secretor samples. Bifidobacterium genus and species were less prevalent in non-secretor samples. Despite no differences on diversity and richness, non-secretor samples had lower Actinobacteria and higher relative abundance of Enterobacteriaceae, Lactobacillaceae, and Staphylococcaceae. CONCLUSIONS: Maternal secretor status is associated with the human milk microbiota composition and is maintained during the first 4 weeks. Specific associations between milk microbiota, HMO, and secretor status were observed, although the potential biological impact on the neonate remains elusive. Future studies are needed to reveal the early nutrition influence on the reduction of risk of disease.
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Fucosiltransferases/metabolismo , Lactação/metabolismo , Leite Humano/química , Leite Humano/microbiologia , Oligossacarídeos/metabolismo , Bifidobacterium/isolamento & purificação , Feminino , Genótipo , Humanos , Lactente , Recém-Nascido , Microbiota , Projetos Piloto , Reação em Cadeia da Polimerase , RNA Ribossômico 16S , Galactosídeo 2-alfa-L-FucosiltransferaseRESUMO
BACKGROUND: Early microbial colonization is a relevant aspect in human health. Altered microbial colonization patterns have been linked to an increased risk of non-communicable diseases (NCDs). Advances in understanding host-microbe interactions highlight the pivotal role of maternal microbiota on infant health programming. This birth cohort is aimed to characterize the maternal microbes transferred to neonates during the first 1000 days of life, as well as to identify the potential host and environmental factors, such as gestational age, mode of delivery, maternal/infant diet, and exposure to antibiotics, which affect early microbial colonization. METHODS: MAMI is a prospective mother-infant birth cohort in the Spanish-Mediterranean area. Mothers were enrolled at the end of pregnancy and families were follow-up during the first years of life. Maternal-infant biological samples were collected at several time points from birth to 24 months of life. Clinical and anthropometric characteristics and dietary information is available. Specific qPCR and 16S rRNA gene sequencing as well as short chain fatty acid (SCFAs) profile would be obtained. Multivariable models will be used to identy associations between microbiota and clinical and anthropometric data controlling for confounders. MAMI would contribute to a better understanding of the interaction between diet, microbiota and host response in early life health programming, enabling new applications in the field of personalized nutrition and medicine. TRIAL REGISTRATION: The study is registered on the ClinicalTrial.gov platform NCT03552939. (June 12, 2018).
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Aleitamento Materno , Dieta , Saúde do Lactente , Monitorização Fisiológica/métodos , Adulto , Fatores Etários , Desenvolvimento Infantil , Estudos de Coortes , DNA/genética , Feminino , Microbioma Gastrointestinal , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Masculino , Relações Mãe-Filho , Análise Multivariada , Reação em Cadeia da Polimerase/métodos , Estudos Prospectivos , Fatores Sexuais , EspanhaRESUMO
OBJECTIVES: Human milk oligosaccharides (HMOs) are considered to play an important role for the infant. As the biotechnical production of some HMOs is feasible today and clinical studies are being designed, the individual variation of the total amount of HMOs and of single components is of particular importance. Our objectives were to investigate whether differences exist between term and preterm milk, milk from mothers with secretor or nonsecretor status, and a Lewis blood group (a+b-), (a-b+), or (a-b-) pattern. METHODS: Within a longitudinal study 96 milk samples (colostrum, transitional, and mature milk) from 32 mothers with preterm (nâ=â18) and term (nâ=â14) infants were collected. Delipidated and deproteinized milk was subjected to porous graphitized carbon cartridges followed by high pH anion exchange chromatography with pulsed amperometric detection. RESULTS: Quantitation of 16 single HMOs revealed changes during the first weeks of lactation without discrepancies between term and preterm milk. Significant differences occurred between "secretor" and "nonsecretor" milk (median approximately 10 vs 5 g/L total HMOs). Lacto-N-tetraose (LNT) and lacto-N-fucopentaose (LNFP) II comprised > 55% of the total HMO content in Lewis blood group (a+b-), "nonsecretor" milk and LNT together with 2'fucosyllactose, LNFP I, and difucosyllactose approximately 60% in Lewis (a-b+), "secretor" milk. In Lewis (a-b-), "secretor" milk 80% of oligosaccharides are due to LNT, 2'fucosyllactose, and LNFP I. CONCLUSIONS: There are marked differences in total HMOs and single HMOs in milk depending on Lewis blood group and secretor status, which need to be taken into account in clinical studies.
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Idade Gestacional , Antígenos do Grupo Sanguíneo de Lewis , Leite Humano/química , Oligossacarídeos/metabolismo , Feminino , Voluntários Saudáveis , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Estudos Longitudinais , Estudos ProspectivosRESUMO
OBJECTIVE: To receive stakeholders' feedback on the new structure of the Nutritional Disorders section of the International Classification of Diseases, 11th Revision (ICD-11). DESIGN: A twenty-five-item survey questionnaire on the ICD-11 Nutritional Disorders section was developed and sent out via email. The international online survey investigated participants' current use of the ICD and their opinion of the new structure being proposed for ICD-11. The LimeSurvey® software was used to conduct the survey. Summary statistical analyses were performed using the survey tool. SETTING: Worldwide. SUBJECTS: Individuals subscribed to the mailing list of the WHO Department of Nutrition for Health and Development. RESULTS: Seventy-two participants currently using the ICD, mainly nutritionists, public health professionals and medical doctors, completed the questionnaire (response rate 16 %). Most participants (n 69) reported the proposed new structure will be a useful improvement over ICD-10 and 78 % (n 56) considered that all nutritional disorders encountered in their work were represented. Overall, participants expressed satisfaction with the comprehensiveness, clarity and life cycle approach. Areas identified for improvement before ICD-11 is finalized included adding some missing disorders, more clarity on the transition to new terminology, links to other classifications and actions to address the disorders. CONCLUSIONS: The Nutritional Disorders section being proposed for ICD-11 offers significant improvements compared with ICD-10. The new taxonomy and inclusion of currently missing entities is expected to enhance the classification and health-care professionals' accurate coding of the full range of nutritional disorders throughout the life cycle.
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Pessoal de Saúde , Classificação Internacional de Doenças , Distúrbios Nutricionais/classificação , Humanos , Inquéritos e QuestionáriosRESUMO
Resistance to antibiotics in newborns is a huge concern as their immune system is still developing, and infections and resistance acquisition in early life have short- and long-term consequences for their health. Bifidobacterium species are important commensals capable of dominating the infant gut microbiome and are known to be less prone to possess antimicrobial resistance genes than other taxa that may colonize infants. We aimed to study the association between Bifidobacterium-dominated infant gut microbiota and the antibiotic resistant gene load in neonates, and to ascertain the perinatal factors that may contribute to the antibiotic resistance acquisition. Two hundred infant fecal samples at 7 days and 1 month of age from the MAMI birth cohort were included in the study and for whom maternal-neonatal clinical records were available. Microbiota profiling was carried out by 16S rRNA amplicon sequencing, and targeted antibiotic resistance genes (ARGs) including tetM, tetW, tetO, blaTEM, blaSHV and ermB were quantified by qPCR. Infant microbiota clustered into two distinct groups according to their Bifidobacterium genus abundance: high and low. The main separation of groups or clusters at each time point was performed with an unsupervised non-linear algorithm of k-means partitioning to cluster data by time points based on Bifidobacterium genus relative abundance. Microbiota composition differed significantly between both groups, and specific bifidobacterial species were enriched in each cluster. Lower abundance of Bifidobacterium in the infant gut was associated with a higher load of antibiotic resistance genes. Our results highlight the relevance of Bifidobacterium genus in the early acquisition and establishment of antibiotic resistance in the gut. Further studies are needed to develop strategies to promote a healthy early colonization and fight against the spread of antibiotic resistances.
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Antibacterianos , Bifidobacterium , Farmacorresistência Bacteriana , Fezes , Microbioma Gastrointestinal , RNA Ribossômico 16S , Humanos , Bifidobacterium/genética , Bifidobacterium/efeitos dos fármacos , Bifidobacterium/isolamento & purificação , Recém-Nascido , Microbioma Gastrointestinal/efeitos dos fármacos , Fezes/microbiologia , Antibacterianos/farmacologia , Feminino , RNA Ribossômico 16S/genética , Farmacorresistência Bacteriana/genética , Masculino , LactenteRESUMO
The composition and maturation of the early-life microbiota are modulated by a number of perinatal factors, whose interplay in relation to microbial vertical transmission remains inadequately elucidated. Using recent strain-tracking methodologies, we analyzed mother-to-infant microbiota transmission in two different birth environments: hospital-born (vaginal/cesarean) and home-born (vaginal) infants and their mothers. While delivery mode primarily explains initial compositional differences, place of birth impacts transmission timing-being early in homebirths and delayed in cesarean deliveries. Transmission patterns vary greatly across species and birth groups, yet certain species, like Bifidobacterium longum, are consistently vertically transmitted regardless of delivery setting. Strain-level analysis of B. longum highlights relevant and consistent subspecies replacement patterns mainly explained by breastfeeding practices, which drive changes in human milk oligosaccharide (HMO) degrading capabilities. Our findings highlight how delivery setting, breastfeeding duration, and other lifestyle preferences collectively shape vertical transmission, impacting infant gut colonization during early life.
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Aleitamento Materno , Leite Humano , Humanos , Feminino , Leite Humano/microbiologia , Recém-Nascido , Lactente , Microbioma Gastrointestinal/fisiologia , Microbiota/fisiologia , Adulto , Bifidobacterium , Transmissão Vertical de Doenças Infecciosas , GravidezRESUMO
OBJECTIVE: There is sufficient evidence on the feasibility of a vaccine to prevent Helicobacter pylori infection. Modeling studies in low prevalence environments report a very probable long-term cost-effectiveness. The objective of this study was to quantify its efficiency in a local context. METHODS: The evolution of a cohort of newborns was simulated through a compartmental model representing a series of clinical situations regarding H. pylori infection and related diseases. The model was run under the assumption of both vaccination in the first year of life and no intervention. The time horizon was set as equivalent to the life expectancy and the perspective of the health system was taken into account. RESULTS: Vaccination against H. pylori would cost an average of 2,168/person more than no intervention. This would yield an average additional 0.32 quality-adjusted life years gained (QALY), which would entail an incremental cost-effectiveness ratio (ICER) of 7,196/QALY. For a willingness to pay of 24,506/QALY, 99.96% of the simulations were cost-effective at eighty-four years old. This threshold was crossed thirty years after vaccination. The variables that carried the most weight in explaining the variability of the ICER were, in this order, vaccine effectiveness, the incidence of infection in young children, and the price of the vaccine. Vaccination would cease to be cost-effective with a price greater than 3,634/dose or with effective population coverage less than 11%. CONCLUSIONS: When implemented in an environment with the epidemiological and economic characteristics of Southern Europe, a prophylactic vaccination against H. pylori would be cost-effective in the long run.
OBJECTIVE: Existen pruebas de la factibilidad de una vacuna para prevenir la infección por Helicobacter pylori. Modelizaciones en entornos de baja prevalencia informan de una muy probable coste-efectividad a largo plazo. El objetivo de este estudio fue cuantificar su eficiencia en un contexto local. METHODS: Se simuló la evolución de una cohorte de nacidos a través de un modelo compartimental representativo de varios estados clínicos en relación a la infección por H. pylori. Se ejecutó dicho modelo bajo las premisas de vacunación en el periodo de lactante y de no intervención. El horizonte temporal fue equivalente a la esperanza de vida y se tuvo en cuenta la perspectiva del sistema de salud. RESULTS: La vacunación frente a H. pylori costaría de media 2.168 /persona más que la no intervención. Con ello se obtendrían 0,32 años de vida ganados ajustados por calidad (AVAC), lo que implicaría una razón de coste-efectividad incremental (RCEI) media de 7.196 /AVAC. Para una disposición a pagar de 24.506 /AVAC, el 99,96% de las simulaciones resultaron coste-efectivas al alcanzar el horizonte temporal y se cruzó dicho umbral a partir de los treinta años de la vacunación. Las variables que más peso tuvieron para explicar la variabilidad de la RCEI fueron, en este orden, la efectividad vacunal, la incidencia de la infección en la primera infancia y el precio de la vacuna. La vacunación dejaría de ser coste-efectiva con un precio mayor de 3.634/vial o con una cobertura poblacional efectiva menor del 11%. CONCLUSIONS: Una vacunación frente a la infección por H. pylori administrada en la infancia sería coste-efectiva a largo plazo en un entorno con las características epidemiológicas y económicas del sur de Europa.
Assuntos
Infecções por Helicobacter , Helicobacter pylori , Vacinas , Criança , Humanos , Recém-Nascido , Pré-Escolar , Idoso de 80 Anos ou mais , Análise de Custo-Efetividade , Análise Custo-Benefício , Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/prevenção & controle , Espanha , Europa (Continente) , Anos de Vida Ajustados por Qualidade de VidaRESUMO
OBJECTIVE: To examine the association between cardiovascular risk and childhood overweight and obesity using the BMI cut-offs recommended by the WHO. DESIGN: Children were classified as normal weight, overweight and obese according to the WHO BMI-for-age reference. Blood pressure, lipids, glucose, insulin, homeostasis model assessment-insulin resistance (HOMA-IR) and uric acid levels were compared across BMI groups. ANOVA and tests of linearity were used to assess overall mean differences across groups. Crude and adjusted odds ratios were calculated for adverse plasma levels of biochemical variables. SETTING: Paediatric care centres. SUBJECTS: Children (n 149) aged 8-18 years. RESULTS: About 37 %, 22 % and 41 % of children were classified respectively as normal weight, overweight and obese. There were significant linear mean differences between BMI groups in systolic blood pressure, HDL-cholesterol, TAG, insulin, HOMA-IR and uric acid. Obese children were 10·6 times more likely than normal-weight children to have hypertension; OR for other associations were 60·2 (high insulin), 39·5 (HOMA-IR), 27·9 (TAG), 16·0 (HDL-cholesterol), 4·3 (LDL-cholesterol) and 3·6 (uric acid). Overweight children were more likely than normal-weight children to have hypertension (OR = 3·5), high insulin (OR = 28·2), high HOMA-IR (OR = 23·3) and high TAG (OR = 16·1). Nearly 92 % and 57 % of the obese and overweight children, respectively, had one or more risk factor. CONCLUSIONS: Obesity and overweight defined using the WHO BMI-for-age cut-offs identified children with higher metabolic and vascular risk. These results emphasize the importance of prevention of overweight and obesity in childhood to reduce cardiovascular risk.
Assuntos
Doenças Cardiovasculares/epidemiologia , Obesidade/epidemiologia , Sobrepeso/epidemiologia , Organização Mundial da Saúde , Adolescente , Glicemia/análise , Pressão Sanguínea , Índice de Massa Corporal , Doenças Cardiovasculares/etiologia , Criança , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Análise por Conglomerados , Feminino , Seguimentos , Humanos , Hipertensão/epidemiologia , Hipertensão/etiologia , Insulina/sangue , Resistência à Insulina , Modelos Logísticos , Masculino , Análise Multivariada , Obesidade/complicações , Sobrepeso/complicações , Estudos Prospectivos , Fatores de Risco , Espanha/epidemiologia , Ácido Úrico/sangueRESUMO
BACKGROUND: Maternal diet influences the milk composition, yet little information is available on the impact of maternal diet on milk miRNAs expression. Further, the association of human milk miRNAs to maternal diet and milk microbiota is not explored. In addition, the role of milk miRNAs on the infant gut microbiota, infant growth and development has not been investigated. METHODS: Milk samples were collected from 60 healthy lactating women at ≤15d post-partum, HTG transcriptome assay was performed to examine milk miRNA profile. Maternal clinical and dietary clusters information were available and infant anthropometric measures were followed up to one year of age. Milk and infant microbiota were analyzed by 16S rRNA gene sequencing and integrative multi-omics data analysis was performed to identify potential association between microRNA, maternal dietary nutrients and microbiota. RESULTS: Discriminant analysis revealed that the milk miRNAs were clustered into groups according to the maternal protein source. Interestingly, 31 miRNAs were differentially expressed (P adj < 0.05) between maternal dietary clusters (Cluster 1: enriched in plant protein and fibers and Cluster 2: enriched in animal protein), with 30 miRNAs downregulated in the plant protein group relative to animal protein group. Pathway analysis revealed that the top enriched pathways (P adj < 0.01) were involved in cell growth and proliferation processes. Furthermore, significant features contributing to the clustering were associated with maternal dietary nutrients and milk microbiota (r > 0.70). Further, miR-378 and 320 family miRNAs involved in adipogenesis were positively correlated to the infant BMI-z-scores, weight, and weight for length-z-scores at 6 months of age. CONCLUSIONS: Maternal dietary source impacts the milk miRNA expression profile. Further, miRNAs were associated with maternal dietary nutrients, milk microbiota and to the infant gut microbiota and infant growth and development. CLINICAL TRIAL: The study is registered in ClinicalTrials.gov. The identification number is NCT03552939.
Assuntos
Microbioma Gastrointestinal , MicroRNAs , Feminino , Humanos , Lactente , Dieta , Microbioma Gastrointestinal/genética , Lactação , MicroRNAs/genética , Leite Humano/metabolismo , Nutrientes , Proteínas de Plantas , RNA Ribossômico 16S/genéticaRESUMO
Breast milk (BM) is important for adequate infant development, and it contains bioactive compounds, such as bacteria, cytokines and some adipokines which play a role in infant microbial, metabolic, and immunological maturation. However, little is known about its impact on growth and development in early life. The objective of this study was to evaluate the impact of milk microbiota, cytokine, and adipokine profiles on the risk of overweight at 12 months of life to find the possible mechanisms of host-microbe interactions. In this study, BM samples from 100 healthy women collected during 15 d after birth were included. BM microbiota was analysed by 16S rRNA gene sequencing, and cytokine and adipokine levels were measured by the Luminex approach. In addition, infant weight and length were recorded during the first 12 months and z-scores were obtained according to the WHO databases. Infants were classified as risk of overweight (ROW) and no-risk of overweight (NOROW) based on their body mass index z-score (BMIZ) and infant weight-for-length z-score (WLZ) at 12 months. In order to study host-microbe interactions, epithelial intestinal and mammary cell lines were exposed to milk microbes to assess the host response by interleukin (IL)-6 production as a potential inflammatory marker. BM was dominated by Staphylococcus and Streptococcus genera, and the most abundant cytokines were IL-6 and IL-18. Leptin levels were positively correlated with the pregestational body mass index (BMI). Higher relative abundance of the Streptococcus genus was associated with higher IL-10 and higher relative abundance of the Bifidobacterium genus was associated with lower IL-6 concentrations in milk. Infant WLZ at 12 months could be partially predicted by Streptococcus genus proportions and IL-10 and IL-18 levels in BM. BM microbiota significantly induced cytokine responses in mammary epithelial cells. Higher levels of IL-6 production were observed in mammary cells exposed to BM microbiota from mothers with ROW offspring compared to mothers with NOROW offspring. In conclusion, BM microbiota is related to the cytokine profile. IL-10 and IL-18 levels and the abundance of the Streptococcus genus could affect early infant development. Further research is needed to clarify the specific impact of BM microbiota and cytokines on infant growth and the risk of overweight.