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1.
Semin Perinatol ; : 151408, 2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-33875265

RESUMO

To understand the disparities in spontaneous preterm birth (sPTB) and/or its outcomes, biologic and social determinants as well as healthcare practice (such as those in neonatal intensive care units) should be considered. They have been largely intractable and remain obscure in most cases, despite a myriad of identified risk factors for and causes of sPTB. We still do not know how they might actually affect and lead to the different outcomes at different gestational ages and if they are independent of NICU practices. Here we describe an integrated approach to study the interplay between the genome and exposome, which may drive biochemistry and physiology, with health disparities.

2.
Microbiome ; 9(1): 8, 2021 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-33436098

RESUMO

For more than a century, the prenatal environment was considered sterile. Over the last few years, findings obtained with next-generation sequencing approaches from samples of the placenta, the amniotic fluid, meconium, and even fetal tissues have challenged the dogma of a sterile womb, and additional reports have emerged that used culture, microscopy, and quantitative PCR to support the presence of a low-biomass microbial community at prenatal sites. Given the substantial implications of prenatal exposure to microbes for the development and health of the host, the findings have gathered substantial interest from academics, high impact journals, the public press, and funding agencies. However, an increasing number of studies have challenged the prenatal microbiome identifying contamination as a major issue, and scientists that remained skeptical have pointed to inconsistencies with in utero colonization, the impact of c-sections on early microbiome assembly, and the ability to generate germ-free mammals. A lively academic controversy has emerged on the existence of the wider importance of prenatal microbial communities. Microbiome has asked experts to discuss these issues and provide their thoughts on the implications. To allow for a broader perspective of this discussion, we have specifically selected scientists, who have a long-standing expertise in microbiome sciences but who have not directly been involved in the debate so far.


Assuntos
Dissidências e Disputas , Feto/microbiologia , Microbiota/fisiologia , Modelos Biológicos , Líquido Amniótico/microbiologia , Animais , Feminino , Vida Livre de Germes , Humanos , Recém-Nascido , Mecônio/microbiologia , Placenta/microbiologia , Gravidez , Útero/microbiologia
3.
Nat Commun ; 11(1): 6294, 2020 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-33293537

RESUMO

Biology can be misused, and the risk of this causing widespread harm increases in step with the rapid march of technological progress. A key security challenge involves attribution: determining, in the wake of a human-caused biological event, who was responsible. Recent scientific developments have demonstrated a capability for detecting whether an organism involved in such an event has been genetically modified and, if modified, to infer from its genetic sequence its likely lab of origin. We believe this technique could be developed into powerful forensic tools to aid the attribution of outbreaks caused by genetically engineered pathogens, and thus protect against the potential misuse of synthetic biology.

4.
Proc Natl Acad Sci U S A ; 117(47): 29246-29248, 2020 11 24.
Artigo em Inglês | MEDLINE | ID: mdl-33144498
5.
Nat Commun ; 11(1): 3772, 2020 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-32728114

RESUMO

Selective and neutral forces shape human microbiota assembly in early life. The Tsimane are an indigenous Bolivian population with infant care-associated behaviors predicted to increase mother-infant microbial dispersal. Here, we characterize microbial community assembly in 47 infant-mother pairs from six Tsimane villages, using 16S rRNA gene amplicon sequencing of longitudinal stool and tongue swab samples. We find that infant consumption of dairy products, vegetables, and chicha (a fermented drink inoculated with oral microbes) is associated with stool microbiota composition. In stool and tongue samples, microbes shared between mothers and infants are more abundant than non-shared microbes. Using a neutral model of community assembly, we find that neutral processes alone explain the prevalence of 79% of infant-colonizing microbes, but explain microbial prevalence less well in adults from river villages with more regular access to markets. Our results underscore the importance of neutral forces during microbiota assembly. Changing lifestyle factors may alter traditional modes of microbiota assembly by decreasing the role of neutral processes.


Assuntos
Horticultura , Povos Indígenas , Microbiota , Adolescente , Adulto , Bolívia , Criança , Pré-Escolar , DNA Bacteriano/isolamento & purificação , Fezes/microbiologia , Feminino , Humanos , Lactente , Recém-Nascido , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Filogenia , RNA Ribossômico 16S/genética , Língua/microbiologia , Adulto Jovem
6.
Microbiol Resour Announc ; 9(20)2020 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-32409537

RESUMO

Lactobacillus iners is a common member of the human vaginal microbiota, with a genome size smaller than that of other lactobacilli. Here, we report the complete genome sequences of six L. iners strains isolated from different vaginal swab specimens. Three strains were found to harbor ∼100-kbp plasmids, which were not known previously.

7.
Mol Cell ; 78(4): 570-576, 2020 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-32442503

RESUMO

Co-evolution of gut commensal bacteria and humans has ensured that the micronutrient needs of both parties are met. This minireview summarizes the known molecular mechanisms of iron, zinc, and B vitamin processing by human-associated bacteria, comparing gut pathogens and commensals, and highlights the tension between their roles as competitors versus collaborators with the human host.


Assuntos
Bactérias/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/efeitos dos fármacos , Micronutrientes/farmacologia , Humanos
9.
Curr Opin Microbiol ; 54: 119-126, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32114367

RESUMO

Relationships between hosts and host-associated microbial communities are complex, intimate, and associated with a wide variety of health and disease states. For these reasons, these relationships have raised many difficult questions and claims about microbiome causation. While philosophers and scientists alike have pondered the challenges of causal inference and offered postulates and rules, there are no simple solutions, especially with poorly characterized, putative causal factors such as microbiomes, ill-defined host effects, and inadequate experimental models. Recommendations are provided here for conceptual and experimental approaches regarding microbiome causal inference, and for a research agenda.

10.
Semin Immunopathol ; 42(4): 397-412, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32020337

RESUMO

Preterm birth is the leading cause of mortality in children under the age of five worldwide. Despite major efforts, we still lack the ability to accurately predict and effectively prevent preterm birth. While multiple factors contribute to preterm labor, dysregulations of immunological adaptations required for the maintenance of a healthy pregnancy is at its pathophysiological core. Consequently, a precise understanding of these chronologically paced immune adaptations and of the biological pacemakers that synchronize the pregnancy "immune clock" is a critical first step towards identifying deviations that are hallmarks of peterm birth. Here, we will review key elements of the fetal, placental, and maternal pacemakers that program the immune clock of pregnancy. We will then emphasize multiomic studies that enable a more integrated view of pregnancy-related immune adaptations. Such multiomic assessments can strengthen the biological plausibility of immunological findings and increase the power of biological signatures predictive of preterm birth.

11.
Nature ; 578(7795): 425-431, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32051592

RESUMO

Bacteriophages typically have small genomes1 and depend on their bacterial hosts for replication2. Here we sequenced DNA from diverse ecosystems and found hundreds of phage genomes with lengths of more than 200 kilobases (kb), including a genome of 735 kb, which is-to our knowledge-the largest phage genome to be described to date. Thirty-five genomes were manually curated to completion (circular and no gaps). Expanded genetic repertoires include diverse and previously undescribed CRISPR-Cas systems, transfer RNAs (tRNAs), tRNA synthetases, tRNA-modification enzymes, translation-initiation and elongation factors, and ribosomal proteins. The CRISPR-Cas systems of phages have the capacity to silence host transcription factors and translational genes, potentially as part of a larger interaction network that intercepts translation to redirect biosynthesis to phage-encoded functions. In addition, some phages may repurpose bacterial CRISPR-Cas systems to eliminate competing phages. We phylogenetically define the major clades of huge phages from human and other animal microbiomes, as well as from oceans, lakes, sediments, soils and the built environment. We conclude that the large gene inventories of huge phages reflect a conserved biological strategy, and that the phages are distributed across a broad bacterial host range and across Earth's ecosystems.


Assuntos
Bactérias/virologia , Bacteriófagos/classificação , Bacteriófagos/genética , Planeta Terra , Ecossistema , Genoma Viral/genética , Filogenia , Aminoacil-tRNA Sintetases/genética , Animais , Bactérias/genética , Bacteriófagos/isolamento & purificação , Bacteriófagos/metabolismo , Biodiversidade , Sistemas CRISPR-Cas/genética , Evolução Molecular , Regulação Bacteriana da Expressão Gênica , Regulação Viral da Expressão Gênica , Especificidade de Hospedeiro , Humanos , Lagos/virologia , Anotação de Sequência Molecular , Oceanos e Mares , Prófagos/genética , Biossíntese de Proteínas , RNA de Transferência/genética , Proteínas Ribossômicas/genética , Água do Mar/virologia , Microbiologia do Solo , Transcrição Genética
12.
Periodontol 2000 ; 82(1): 26-41, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31850642

RESUMO

In humans, the composition of microbial communities differs among body sites and between habitats within a single site. Patterns of variation in the distribution of organisms across time and space are referred to as "biogeography." The human oral cavity is a critical observatory for exploring microbial biogeography because it is spatially structured, easily accessible, and its microbiota has been linked to the promotion of both health and disease. The biogeographic features of microbial communities residing in spatially distinct, but ecologically similar, environments on the human body, including the subgingival crevice, have not yet been adequately explored. The purpose of this paper is twofold. First, we seek to provide the dental community with a primer on biogeographic theory, highlighting its relevance to the study of the human oral cavity. We summarize what is known about the biogeographic variation of dental caries and periodontitis and postulate that disease occurrence reflects spatial patterning in the composition and structure of oral microbial communities. Second, we present a number of methods that investigators can use to test specific hypotheses using biogeographic theory. To anchor our discussion, we apply each method to a case study and examine the spatial variation of the human subgingival microbiota in 2 individuals. Our case study suggests that the composition of subgingival communities may conform to an anterior-to-posterior gradient within the oral cavity. The gradient appears to be structured by both deterministic and nondeterministic processes, although additional work is needed to confirm these findings. A better understanding of biogeographic patterns and processes will lead to improved efficacy of dental interventions targeting the oral microbiota.


Assuntos
Cárie Dentária , Microbiota , Doenças Periodontais , Periodontite , Humanos , Boca
13.
Nat Microbiol ; 5(2): 343-353, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31873203

RESUMO

Despite the importance of horizontal gene transfer for rapid bacterial evolution, reliable assignment of mobile genetic elements to their microbial hosts in natural communities such as the human gut microbiota is lacking. We used high-throughput chromosomal conformation capture coupled with probabilistic modelling of experimental noise to resolve 88 strain-level metagenome-assembled genomes of distal gut bacteria from two participants, including 12,251 accessory elements. Comparisons of two samples collected 10 years apart for each of the participants revealed extensive in situ exchange of accessory elements as well as evidence of adaptive evolution in core genomes. Accessory elements were predominantly promiscuous and prevalent in the distal gut metagenomes of 218 adult individuals. This research provides a foundation and approach for studying microbial evolution in natural environments.


Assuntos
Microbioma Gastrointestinal/genética , Microbioma Gastrointestinal/fisiologia , Adaptação Fisiológica/genética , Adulto , Simulação por Computador , Evolução Molecular , Transferência Genética Horizontal , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Metagenoma , Modelos Genéticos , Filogenia , Fatores de Tempo
14.
Front Microbiol ; 10: 2291, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31649637

RESUMO

Iron overload disorder (IOD) affects many wildlife species cared for ex situ. Two of the four rhinoceros species in human care, Sumatran rhinoceros (Dicerorhinus sumatrensis) and black rhinoceros (Diceros bicornis), are susceptible, whereas the other two, white rhinoceros (Ceratotherium simum) and greater one-horned (GOH) rhinoceros (Rhinoceros unicornis), are relatively resistant to IOD. Complex interrelationships exist between mammalian hosts, their indigenous gut microbiota, metabolome, physical condition, and iron availability. The goal of this study was to gain insight into these relationships within the family Rhinocerotidae. Specific objectives were to (1) characterize the gut microbiome and metabolome of four rhinoceros species; (2) compare the microbiome and metabolome of IOD-susceptible and IOD-resistant rhinoceros species; and (3) identify variation in the microbiome and metabolome associated with compromised health or disease in IOD-susceptible rhinoceroses. Fecal samples were collected from 31 rhinoceroses (Sumatran rhinoceros, n = 3; black rhinoceros, n = 6; GOH rhinoceros, n = 9; white rhinoceros, n = 13) located at five facilities, and matched fecal aliquots were processed for microbiome and metabolome analyses using 16S rRNA gene sequencing and nuclear magnetic resonance spectroscopy, respectively. Despite the phylogenetic disparity and dissimilar zoo diets of the hosts, the structure of the fecal microbiota of the two IOD-susceptible rhinoceros species were more closely related to each other than to those of the two IOD-resistant species (Bray-Curtis dissimilarity; IOD-susceptible vs. IOD-resistant p-value < 0.001). In addition, IOD-susceptible rhinoceroses exhibited less microbial diversity than their IOD-resistant relatives (Shannon diversity; p-value < 0.001) which could have health implications. Of note, the black rhinoceros was distinct among the four rhinoceros species with the most divergent fecal metabolome; interestingly, it contained higher concentrations of short chain fatty acids. Neither age nor sex were associated with differences in microbial community composition (p = 0.253 and 0.488, respectively) or fecal metabolomic profile (p = 0.634 and 0.332, respectively). Differences in the distal gut microbiomes between IOD-resistant and IOD-susceptible rhinoceroses support hypotheses that gut microbes play a role in host iron acquisition, and further studies and experiments to test these hypotheses are warranted.

15.
Immunity ; 51(2): 211-213, 2019 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-31433968

RESUMO

In a recent issue of Nature Medicine, Gopalakrishna et al. show that altered patterns of IgA binding to gut bacteria in premature infants are associated with necrotizing enterocolitis, underscoring the critical role of host mucosal immunity in shaping the microbiota.


Assuntos
Enterocolite Necrosante , Microbiota , Criança , Pré-Escolar , Humanos , Imunidade nas Mucosas , Imunoglobulina A , Lactente , Recém-Nascido , Recém-Nascido Prematuro
16.
Inflamm Bowel Dis ; 25(12): 1927-1938, 2019 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-31276165

RESUMO

BACKGROUND: The beneficial effects of antibiotics in Crohn's disease (CD) depend in part on the gut microbiota but are inadequately understood. We investigated the impact of metronidazole (MET) and metronidazole plus azithromycin (MET+AZ) on the microbiota in pediatric CD and the use of microbiota features as classifiers or predictors of disease remission. METHODS: 16S rRNA-based microbiota profiling was performed on stool samples from 67 patients in a multinational, randomized, controlled, longitudinal, 12-week trial of MET vs MET+AZ in children with mild to moderate CD. Profiles were analyzed together with disease activity, and then used to construct random forest models to classify remission or predict treatment response. RESULTS: Both MET and MET+AZ significantly decreased diversity of the microbiota and caused large treatment-specific shifts in microbiota structure at week 4. Disease remission was associated with a treatment-specific microbiota configuration. Random forest models constructed from microbiota profiles before and during antibiotic treatment with metronidazole accurately classified disease remission in this treatment group (area under the curve [AUC], 0.879; 95% confidence interval, 0.683-0.9877; sensitivity, 0.7778; specificity, 1.000; P < 0.001). A random forest model trained on pre-antibiotic microbiota profiles predicted disease remission at week 4 with modest accuracy (AUC, 0.8; P = 0.24). CONCLUSIONS: MET and MET+AZ antibiotic regimens in pediatric CD lead to distinct gut microbiota structures at remission. It may be possible to classify and predict remission based in part on microbiota profiles, but larger cohorts will be needed to realize this goal.


Assuntos
Antibacterianos/uso terapêutico , Azitromicina/uso terapêutico , Doença de Crohn/tratamento farmacológico , Microbioma Gastrointestinal/efeitos dos fármacos , Metronidazol/uso terapêutico , Adolescente , Criança , Pré-Escolar , Quimioterapia Combinada , Feminino , Humanos , Masculino , RNA Ribossômico 16S/análise , Indução de Remissão , Resultado do Tratamento
17.
J Perinatol ; 39(3): 354-358, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30560947

RESUMO

Based upon our recent insights into the determinants of preterm birth, which is the leading cause of death in children under five years of age worldwide, we describe potential analytic frameworks that provides both a common understanding and, ultimately the basis for effective, ameliorative action. Our research on preterm birth serves as an example that the framing of any human health condition is a result of complex interactions between the genome and the exposome. New discoveries of the basic biology of pregnancy, such as the complex immunological and signaling processes that dictate the health and length of gestation, have revealed a complexity in the interactions (current and ancestral) between genetic and environmental forces. Understanding of these relationships may help reduce disparities in preterm birth and guide productive research endeavors and ultimately, effective clinical and public health interventions.


Assuntos
Meio Ambiente , Predisposição Genética para Doença , Disparidades nos Níveis de Saúde , Complicações na Gravidez/etiologia , Nascimento Prematuro/etiologia , Feminino , Humanos , Gravidez , Nascimento Prematuro/epidemiologia , Saúde Pública , Fatores de Risco
18.
Bioinformatics ; 35(1): 95-103, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30561547

RESUMO

Motivation: Multiple biological clocks govern a healthy pregnancy. These biological mechanisms produce immunologic, metabolomic, proteomic, genomic and microbiomic adaptations during the course of pregnancy. Modeling the chronology of these adaptations during full-term pregnancy provides the frameworks for future studies examining deviations implicated in pregnancy-related pathologies including preterm birth and preeclampsia. Results: We performed a multiomics analysis of 51 samples from 17 pregnant women, delivering at term. The datasets included measurements from the immunome, transcriptome, microbiome, proteome and metabolome of samples obtained simultaneously from the same patients. Multivariate predictive modeling using the Elastic Net (EN) algorithm was used to measure the ability of each dataset to predict gestational age. Using stacked generalization, these datasets were combined into a single model. This model not only significantly increased predictive power by combining all datasets, but also revealed novel interactions between different biological modalities. Future work includes expansion of the cohort to preterm-enriched populations and in vivo analysis of immune-modulating interventions based on the mechanisms identified. Availability and implementation: Datasets and scripts for reproduction of results are available through: https://nalab.stanford.edu/multiomics-pregnancy/. Supplementary information: Supplementary data are available at Bioinformatics online.


Assuntos
Metaboloma , Microbiota , Gravidez , Proteoma , Transcriptoma , Biologia Computacional , Feminino , Humanos
19.
Microbiome ; 6(1): 226, 2018 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-30558668

RESUMO

BACKGROUND: The accuracy of microbial community surveys based on marker-gene and metagenomic sequencing (MGS) suffers from the presence of contaminants-DNA sequences not truly present in the sample. Contaminants come from various sources, including reagents. Appropriate laboratory practices can reduce contamination, but do not eliminate it. Here we introduce decontam ( https://github.com/benjjneb/decontam ), an open-source R package that implements a statistical classification procedure that identifies contaminants in MGS data based on two widely reproduced patterns: contaminants appear at higher frequencies in low-concentration samples and are often found in negative controls. RESULTS: Decontam classified amplicon sequence variants (ASVs) in a human oral dataset consistently with prior microscopic observations of the microbial taxa inhabiting that environment and previous reports of contaminant taxa. In metagenomics and marker-gene measurements of a dilution series, decontam substantially reduced technical variation arising from different sequencing protocols. The application of decontam to two recently published datasets corroborated and extended their conclusions that little evidence existed for an indigenous placenta microbiome and that some low-frequency taxa seemingly associated with preterm birth were contaminants. CONCLUSIONS: Decontam improves the quality of metagenomic and marker-gene sequencing by identifying and removing contaminant DNA sequences. Decontam integrates easily with existing MGS workflows and allows researchers to generate more accurate profiles of microbial communities at little to no additional cost.


Assuntos
Bactérias/genética , Marcadores Genéticos , Metagenômica/métodos , Boca/microbiologia , Análise de Sequência de DNA/métodos , Bactérias/classificação , Contaminação por DNA , DNA Bacteriano/genética , DNA Ribossômico/genética , Bases de Dados Genéticas , Humanos , Internet , Modelos Estatísticos , RNA Ribossômico 16S/genética , Software
20.
Proc Natl Acad Sci U S A ; 115(51): 12902-12910, 2018 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-30559176

RESUMO

Reciprocal, intimate relationships between the human microbiome and the host immune system are shaped by past microbial encounters and prepare the host for future ones. Antibiotics and other antimicrobials leave their mark on both the microbiome and host immunity. Antimicrobials alter the structure of the microbiota, expand the host-specific pool of antimicrobial-resistance genes and organisms, degrade the protective effects of the microbiota against invasion by pathogens, and may impair vaccine efficacy. Through these effects on the microbiome they may affect immune responses. Vaccines that exert protective or therapeutic effects against pathogens may reduce the use of antimicrobials, the development and spread of antimicrobial resistance, and the harmful impacts of these drugs on the microbiome. Other strategies involving manipulation of the microbiome to deplete antibiotic-resistant organisms or to enhance immune responses to vaccines may prove valuable in addressing antimicrobial resistance as well. This article describes the intersections of immunity, microbiome and antimicrobial exposure, and the use of vaccines and other alternative strategies for the control and management of antimicrobial resistance.


Assuntos
Anti-Infecciosos/farmacologia , Controle de Doenças Transmissíveis/métodos , Resistência Microbiana a Medicamentos/efeitos dos fármacos , Microbiota/efeitos dos fármacos , Vacinas/uso terapêutico , Doenças Transmissíveis/tratamento farmacológico , Resistência Microbiana a Medicamentos/genética , Interações entre Hospedeiro e Microrganismos/efeitos dos fármacos , Interações entre Hospedeiro e Microrganismos/genética , Interações entre Hospedeiro e Microrganismos/imunologia , Humanos
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