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Common and rare alleles are now being annotated across millions of human genomes, and omics technologies are increasingly being used to develop health and treatment recommendations. However, these alleles have not yet been systematically characterized relative to aerospace medicine. Here, we review published alleles naturally found in human cohorts that have a likely protective effect, which is linked to decreased cancer risk and improved bone, muscular, and cardiovascular health. Although some technical and ethical challenges remain, research into these protective mechanisms could translate into improved nutrition, exercise, and health recommendations for crew members during deep space missions.
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Alelos , Medicina de Precisão , Voo Espacial , Humanos , Medicina de Precisão/métodos , Medicina Aeroespacial , Genoma Humano , Neoplasias/genética , Neoplasias/terapiaRESUMO
The SpaceX Inspiration4 mission provided a unique opportunity to study the impact of spaceflight on the human body. Biospecimen samples were collected from four crew members longitudinally before (Launch: L-92, L-44, L-3 days), during (Flight Day: FD1, FD2, FD3), and after (Return: R + 1, R + 45, R + 82, R + 194 days) spaceflight, spanning a total of 289 days across 2021-2022. The collection process included venous whole blood, capillary dried blood spot cards, saliva, urine, stool, body swabs, capsule swabs, SpaceX Dragon capsule HEPA filter, and skin biopsies. Venous whole blood was further processed to obtain aliquots of serum, plasma, extracellular vesicles and particles, and peripheral blood mononuclear cells. In total, 2,911 sample aliquots were shipped to our central lab at Weill Cornell Medicine for downstream assays and biobanking. This paper provides an overview of the extensive biospecimen collection and highlights their processing procedures and long-term biobanking techniques, facilitating future molecular tests and evaluations.As such, this study details a robust framework for obtaining and preserving high-quality human, microbial, and environmental samples for aerospace medicine in the Space Omics and Medical Atlas (SOMA) initiative, which can aid future human spaceflight and space biology experiments.
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Bancos de Espécimes Biológicos , Voo Espacial , Manejo de Espécimes , Humanos , Manejo de Espécimes/métodos , AstronautasRESUMO
Spaceflight induces an immune response in astronauts. To better characterize this effect, we generated single-cell, multi-ome, cell-free RNA (cfRNA), biochemical, and hematology data for the SpaceX Inspiration4 (I4) mission crew. We found that 18 cytokines/chemokines related to inflammation, aging, and muscle homeostasis changed after spaceflight. In I4 single-cell multi-omics data, we identified a "spaceflight signature" of gene expression characterized by enrichment in oxidative phosphorylation, UV response, immune function, and TCF21 pathways. We confirmed the presence of this signature in independent datasets, including the NASA Twins Study, the I4 skin spatial transcriptomics, and 817 NASA GeneLab mouse transcriptomes. Finally, we observed that (1) T cells showed an up-regulation of FOXP3, (2) MHC class I genes exhibited long-term suppression, and (3) infection-related immune pathways were associated with microbiome shifts. In summary, this study reveals conserved and distinct immune disruptions occurring and details a roadmap for potential countermeasures to preserve astronaut health.
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Análise de Célula Única , Voo Espacial , Transcriptoma , Animais , Feminino , Masculino , Humanos , Camundongos , Astronautas , Citocinas/metabolismo , Linfócitos T/imunologia , Fatores Sexuais , Perfilação da Expressão Gênica , Fosforilação OxidativaRESUMO
Spaceflight induces molecular, cellular and physiological shifts in astronauts and poses myriad biomedical challenges to the human body, which are becoming increasingly relevant as more humans venture into space1-6. Yet current frameworks for aerospace medicine are nascent and lag far behind advancements in precision medicine on Earth, underscoring the need for rapid development of space medicine databases, tools and protocols. Here we present the Space Omics and Medical Atlas (SOMA), an integrated data and sample repository for clinical, cellular and multi-omic research profiles from a diverse range of missions, including the NASA Twins Study7, JAXA CFE study8,9, SpaceX Inspiration4 crew10-12, Axiom and Polaris. The SOMA resource represents a more than tenfold increase in publicly available human space omics data, with matched samples available from the Cornell Aerospace Medicine Biobank. The Atlas includes extensive molecular and physiological profiles encompassing genomics, epigenomics, transcriptomics, proteomics, metabolomics and microbiome datasets, which reveal some consistent features across missions, including cytokine shifts, telomere elongation and gene expression changes, as well as mission-specific molecular responses and links to orthologous, tissue-specific mouse datasets. Leveraging the datasets, tools and resources in SOMA can help to accelerate precision aerospace medicine, bringing needed health monitoring, risk mitigation and countermeasure data for upcoming lunar, Mars and exploration-class missions.
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Maintenance of astronaut health during spaceflight will require monitoring and potentially modulating their microbiomes. However, documenting microbial shifts during spaceflight has been difficult due to mission constraints that lead to limited sampling and profiling. Here we executed a six-month longitudinal study to quantify the high-resolution human microbiome response to three days in orbit for four individuals. Using paired metagenomics and metatranscriptomics alongside single-nuclei immune cell profiling, we characterized time-dependent, multikingdom microbiome changes across 750 samples and 10 body sites before, during and after spaceflight at eight timepoints. We found that most alterations were transient across body sites; for example, viruses increased in skin sites mostly during flight. However, longer-term shifts were observed in the oral microbiome, including increased plaque-associated bacteria (for example, Fusobacteriota), which correlated with immune cell gene expression. Further, microbial genes associated with phage activity, toxin-antitoxin systems and stress response were enriched across multiple body sites. In total, this study reveals in-depth characterization of microbiome and immune response shifts experienced by astronauts during short-term spaceflight and the associated changes to the living environment, which can help guide future missions, spacecraft design and space habitat planning.
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Astronautas , Bactérias , Metagenômica , Microbiota , Voo Espacial , Humanos , Estudos Longitudinais , Microbiota/imunologia , Bactérias/classificação , Bactérias/genética , Bactérias/imunologia , Masculino , Perfilação da Expressão Gênica , Adulto , Pessoa de Meia-Idade , Feminino , Transcriptoma , MultiômicaRESUMO
Spaceflight can change metabolic, immunological, and biological homeostasis and cause skin rashes and irritation, yet the molecular basis remains unclear. To investigate the impact of short-duration spaceflight on the skin, we conducted skin biopsies on the Inspiration4 crew members before (L-44) and after (R + 1) flight. Leveraging multi-omics assays including GeoMx™ Digital Spatial Profiler, single-cell RNA/ATAC-seq, and metagenomics/metatranscriptomics, we assessed spatial gene expressions and associated microbial and immune changes across 95 skin regions in four compartments: outer epidermis, inner epidermis, outer dermis, and vasculature. Post-flight samples showed significant up-regulation of genes related to inflammation and KRAS signaling across all skin regions. These spaceflight-associated changes mapped to specific cellular responses, including altered interferon responses, DNA damage, epithelial barrier disruptions, T-cell migration, and hindered regeneration were located primarily in outer tissue compartments. We also linked epithelial disruption to microbial shifts in skin swab and immune cell activity to PBMC single-cell data from the same crew and timepoints. Our findings present the inaugural collection and examination of astronaut skin, offering insights for future space missions and response countermeasures.
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Inflamação , Proteínas Proto-Oncogênicas p21(ras) , Pele , Voo Espacial , Humanos , Pele/imunologia , Pele/metabolismo , Pele/patologia , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Inflamação/imunologia , Inflamação/genética , Inflamação/metabolismo , Masculino , Análise de Célula Única , Adulto , Pessoa de Meia-Idade , Feminino , Metagenômica/métodos , Perfilação da Expressão Gênica , MultiômicaRESUMO
It is now widely recognised that the environment in space activates a diverse set of genes involved in regulating fundamental cellular pathways. This includes the activation of genes associated with blood homoeostasis and erythropoiesis, with a particular emphasis on those involved in globin chain production. Haemoglobin biology provides an intriguing model for studying space omics, as it has been extensively explored at multiple -omic levels, spanning DNA, RNA, and protein analyses, in both experimental and clinical contexts. In this study, we examined the developmental expression of haemoglobin over time and space using a unique suite of multi-omic datasets available on NASA GeneLab, from the NASA Twins Study, the JAXA CFE study, and the Inspiration4 mission. Our findings reveal significant variations in globin gene expression corresponding to the distinct spatiotemporal characteristics of the collected samples. This study sheds light on the dynamic nature of globin gene regulation in response to the space environment and provides valuable insights into the broader implications of space omics research.
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Hemoglobinas , Humanos , Hemoglobinas/metabolismo , Hemoglobinas/genética , Voo Espacial , Regulação da Expressão Gênica , Eritropoese/genética , Perfilação da Expressão Gênica/métodosRESUMO
Bacteriophages are recognized as the most abundant members of microbiomes and have therefore a profound impact on microbial communities through the interactions with their bacterial hosts. The International Metagenomics and Metadesign of Subways and Urban Biomes Consortium (MetaSUB) has sampled mass-transit systems in 60 cities over 3 years using metagenomics, throwing light into these hitherto largely unexplored urban environments. MetaSUB focused primarily on the bacterial community. In this work, we explored MetaSUB metagenomic data in order to recover and analyze bacteriophage genomes. We recovered and analyzed 1714 phage genomes with size at least 40 kbp, from the class Caudoviricetes, the vast majority of which (80%) are novel. The recovered genomes were predicted to belong to temperate (69%) and lytic (31%) phages. Thirty-three of these genomes have more than 200 kbp, and one of them reaches 572 kbp, placing it among the largest phage genomes ever found. In general, the phages tended to be site-specific or nearly so, but 194 genomes could be identified in every city from which phage genomes were retrieved. We predicted hosts for 48% of the phages and observed general agreement between phage abundance and the respective bacterial host abundance, which include the most common nosocomial multidrug-resistant pathogens. A small fraction of the phage genomes are carriers of antibiotic resistance genes, and such genomes tended to be particularly abundant in the sites where they were found. We also detected CRISPR-Cas systems in five phage genomes. This study expands the previously reported MetaSUB results and is a contribution to the knowledge about phage diversity, global distribution, and phage genome content.
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Bacteriófagos , Microbiota , Ferrovias , Bacteriófagos/genética , Microbiota/genética , Metagenoma/genética , Bactérias/genéticaRESUMO
Introduction: The ancient city of Tel Megiddo in the Jezreel Valley (Israel), which lasted from the Neolithic to the Iron Age, has been continuously excavated since 1903 and is now recognized as a World Heritage Site. The site features multiple ruins in various areas, including temples and stables, alongside modern constructions, and public access is allowed in designated areas. The site has been studied extensively since the last century; however, its microbiome has never been studied. We carried out the first survey of the microbiomes in Tel Megiddo. Our objectives were to study (i) the unique microbial community structure of the site, (ii) the variation in the microbial communities across areas, (iii) the similarity of the microbiomes to urban and archeological microbes, (iv) the presence and abundance of potential bio-corroding microbes, and (v) the presence and abundance of potentially pathogenic microbes. Methods: We collected 40 swab samples from ten major areas and identified microbial taxa using next-generation sequencing of microbial genomes. These genomes were annotated and classified taxonomically and pathogenetically. Results: We found that eight phyla, six of which exist in all ten areas, dominated the site (>99%). The relative sequence abundance of taxa varied between the ruins and the sampled materials and was assessed using all metagenomic reads mapping to a respective taxon. The site hosted unique taxa characteristic of the built environment and exhibited high similarity to the microbiome of other monuments. We identified acid-producing bacteria that may pose a risk to the site through biocorrosion and staining and thus pose a danger to the site's preservation. Differences in the microbiomes of the publicly accessible or inaccessible areas were insignificant; however, pathogens were more abundant in the former. Discussion: We found that Tel Megiddo combines microbiomes of arid regions and monuments with human pathogens. The findings shed light on the microbial community structures and have relevance for bio-conservation efforts and visitor health.
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Maintenance of astronaut health during spaceflight will require monitoring and potentially modulating their microbiomes, which play a role in some space-derived health disorders. However, documenting the response of microbiota to spaceflight has been difficult thus far due to mission constraints that lead to limited sampling. Here, we executed a six-month longitudinal study centered on a three-day flight to quantify the high-resolution microbiome response to spaceflight. Via paired metagenomics and metatranscriptomics alongside single immune profiling, we resolved a microbiome "architecture" of spaceflight characterized by time-dependent and taxonomically divergent microbiome alterations across 750 samples and ten body sites. We observed pan-phyletic viral activation and signs of persistent changes that, in the oral microbiome, yielded plaque-associated pathobionts with strong associations to immune cell gene expression. Further, we found enrichments of microbial genes associated with antibiotic production, toxin-antitoxin systems, and stress response enriched universally across the body sites. We also used strain-level tracking to measure the potential propagation of microbial species from the crew members to each other and the environment, identifying microbes that were prone to seed the capsule surface and move between the crew. Finally, we identified associations between microbiome and host immune cell shifts, proposing both a microbiome axis of immune changes during flight as well as the sources of some of those changes. In summary, these datasets and methods reveal connections between crew immunology, the microbiome, and their likely drivers and lay the groundwork for future microbiome studies of spaceflight.
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Wastewater, which contains everything from pathogens to pollutants, is a geospatially-and temporally-linked microbial fingerprint of a given population. As a result, it can be leveraged for monitoring multiple dimensions of public health across locales and time. Here, we integrate targeted and bulk RNA sequencing (n=1,419 samples) to track the viral, bacterial, and functional content over geospatially distinct areas within Miami Dade County from 2020-2022. First, we used targeted amplicon sequencing (n=966) to track diverse SARS-CoV-2 variants across space and time, and we found a tight correspondence with clinical caseloads from University students (N = 1,503) and Miami-Dade County hospital patients (N = 3,939 patients), as well as an 8-day earlier detection of the Delta variant in wastewater vs. in patients. Additionally, in 453 metatranscriptomic samples, we demonstrate that different wastewater sampling locations have clinically and public-health-relevant microbiota that vary as a function of the size of the human population they represent. Through assembly, alignment-based, and phylogenetic approaches, we also detect multiple clinically important viruses (e.g., norovirus ) and describe geospatial and temporal variation in microbial functional genes that indicate the presence of pollutants. Moreover, we found distinct profiles of antimicrobial resistance (AMR) genes and virulence factors across campus buildings, dorms, and hospitals, with hospital wastewater containing a significant increase in AMR abundance. Overall, this effort lays the groundwork for systematic characterization of wastewater to improve public health decision making and a broad platform to detect emerging pathogens.
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Measuring microbial diversity is traditionally based on microbe taxonomy. Here, in contrast, we aimed to quantify heterogeneity in microbial gene content across 14,183 metagenomic samples spanning 17 ecologies, including 6 human associated, 7 nonhuman host associated, and 4 in other nonhuman host environments. In total, we identified 117,629,181 nonredundant genes. The vast majority of genes (66%) occurred in only one sample (i.e., "singletons"). In contrast, we found 1,864 sequences present in every metagenome, but not necessarily every bacterial genome. Additionally, we report data sets of other ecology-associated genes (e.g., abundant in only gut ecosystems) and simultaneously demonstrated that prior microbiome gene catalogs are both incomplete and inaccurately cluster microbial genetic life (e.g., at gene sequence identities that are too restrictive). We provide our results and the sets of environmentally differentiating genes described above at http://www.microbial-genes.bio. IMPORTANCE The amount of shared genetic elements has not been quantified between the human microbiome and other host- and non-host-associated microbiomes. Here, we made a gene catalog of 17 different microbial ecosystems and compared them. We show that most species shared between environment and human gut microbiomes are pathogens and that prior gene catalogs described as "nearly complete" are far from it. Additionally, over two-thirds of all genes only appear in a single sample, and only 1,864 genes (0.001%) are found in all types of metagenomes. These results highlight the large diversity between metagenomes and reveal a new, rare class of genes, those found in every type of metagenome, but not every microbial genome.
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Microbioma Gastrointestinal , Microbiota , Humanos , Microbiota/genética , Metagenoma/genética , Microbioma Gastrointestinal/genética , Metagenômica/métodos , Genoma BacterianoRESUMO
BACKGROUND: Risk for COVID-19 positivity and hospitalization due to diverse environmental and sociodemographic factors may change as the pandemic progresses. METHODS: We investigated the association of 360 exposures sampled before COVID-19 outcomes for participants in the UK Biobank, including 9268 and 38,837 non-overlapping participants, sampled at July 17, 2020 and February 2, 2021, respectively. The 360 exposures included clinical biomarkers (e.g., BMI), health indicators (e.g., doctor-diagnosed diabetes), and environmental/behavioral variables (e.g., air pollution) measured 10-14 years before the COVID-19 time periods. RESULTS: Here we show, for example, "participant having son and/or daughter in household" was associated with an increase in incidence from 20% to 32% (risk difference of 12%) between timepoints. Furthermore, we find age to be increasingly associated with COVID-19 positivity over time from Risk Ratio [RR] (per 10-year age increase) of 0.81 to 0.6 (hospitalization RR from 1.18 to 2.63, respectively). CONCLUSIONS: Our data-driven approach demonstrates that time of pandemic plays a role in identifying risk factors associated with positivity and hospitalization.
Social, demographic, and environmental factors have been shown to impact whether a person becomes infected following SARS-CoV-2 exposure. However, it is unclear whether the impact of different factors has changed as the pandemic has progressed. Here we analyze 360 factors and whether they are associated with the proportion of people being found to be infected with SARS-CoV-2 across two periods of time in the UK. Overall, we found that different risk factors were associated with testing positive for SARS-CoV-2 infection early in the pandemic compared to later in the pandemic. These results highlight that public health priorities should be adjusted as a consequence of changing risk and susceptibility to infection as the pandemic progresses.
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The human gut microbiome contributes crucial bioactive metabolites that support human health and is sensitive to perturbations from the ingestion of alcohol and antibiotics. We interrogated the response and recovery of human gut microbes after acute alcohol or broad-spectrum antibiotic administration in a gut model simulating the luminal and mucosal colonic environment with an inoculated human microbiome. Both alcohol and antibiotic treatments reduced the production of major short-chain fatty acids (SCFAs) (acetate, propionate, and butyrate), which are established modulators of human health. Treatment with a microbial synbiotic restored and enhanced gut function. Butyrate and acetate production increased by up to 29.7% and 18.6%, respectively, relative to untreated, dysbiotic samples. In parallel, treatment led to increases in the relative abundances of beneficial commensal organisms not found in the synbiotic (e.g., Faecalibacterium prausnitzii and the urolithin-producing organism Gordonibacter pamelaeae) as well as species present in the synbiotic (e.g., Bifidobacterium infantis), suggesting synergistic interactions between supplemented and native microorganisms. These results lead us to conclude that functional shifts in the microbiome, evaluated by both metabolite production and specific taxonomic compositional changes, are an appropriate metric to assess microbiome "recovery" following a dysbiosis-inducing disruption. Overall, these findings support the execution of randomized clinical studies to determine whether a microbial synbiotic can help restore microbiome function after a disruption. IMPORTANCE The human gut microbiome is sensitive to disruptions by common stressors such as alcohol consumption and antibiotic treatment. In this study, we used an in vitro system modeling the gut microbiome to investigate whether treatment with a microbial synbiotic can help restore microbiome function after stress. We find that a complex gut community treated with alcohol or antibiotics showed reduced levels of production of short-chain fatty acids, which are critical beneficial molecules produced by a healthy gut microbiota. Treatment of stressed communities with a microbial synbiotic resulted in the recovery of SCFA production as well as an increase in the abundance of beneficial commensal organisms. Our results suggest that treatment with a microbial synbiotic has the potential to restore healthy gut microbiome function after stress and merits further investigation in clinical studies.
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Microbioma Gastrointestinal , Simbióticos , Humanos , Microbioma Gastrointestinal/fisiologia , Antibacterianos/farmacologia , Etanol , Ácidos Graxos Voláteis/metabolismo , ButiratosRESUMO
BACKGROUND: Oral microbial therapy has been studied as an intervention for a range of gastrointestinal disorders. Though research suggests that microbial exposure may affect the gastrointestinal system, motility, and host immunity in a pediatric population, data have been inconsistent, with most prior studies being in neither a randomized nor placebo-controlled setting. The aim of this randomized, placebo-controlled study was to evaluate the efficacy of a synbiotic on increasing weekly bowel movements (WBMs) in constipated children. METHODS: Sixty-four children (3-17 years of age) were randomized to receive a synbiotic (n = 33) comprising mixed-chain length oligosaccharides and nine microbial strains, or placebo (n = 31) for 84 days. Stool microbiota was analyzed on samples collected at baseline and completion. The primary outcome was a change from baseline of WBMs in the treatment group compared to placebo. RESULTS: Treatment increased (p < 0.05) the number of WBMs in children with low baseline WBMs, despite broadly distinctive baseline microbiome signatures. Sequencing revealed that low baseline microbial richness in the treatment group significantly anticipated improvements in constipation (p = 0.00074). CONCLUSIONS: These findings suggest the potential for (i) multi-species-synbiotic interventions to improve digestive health in a pediatric population and (ii) bioinformatics-based methods to predict response to microbial interventions in children. IMPACT: Synbiotic microbial treatment improved the number of spontaneous weekly bowel movements in children compared to placebo. Intervention induced an increased abundance of bifidobacteria in children, compared to placebo. All administered probiotic species were enriched in the gut microbiome of the intervention group compared to placebo. Baseline microbial richness demonstrated potential as a predictive biomarker for response to intervention.
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Probióticos , Simbióticos , Criança , Humanos , Lactente , Trato Gastrointestinal/microbiologia , Probióticos/uso terapêutico , Constipação Intestinal/terapia , Fezes/microbiologia , Método Duplo-CegoRESUMO
The purpose of the Maleth Program, also known as Project Maleth, is Malta's first space program to evaluate human skin tissue microbiome changes in type 2 diabetes mellitus (T2DM) patients afflicted with diabetic foot ulcers (DFU). This was carried out in both ground-based models and spaceflight. The first mission (Maleth I) under this program was carried out to uncover the effects of spaceflight, microgravity and radiation on human skin tissue microbiome samples from six T2DM patients recruited into the study. Each patient human skin tissue sample was split in three, with one section processed immediately for genomic profiling by 16S typing and the rest were processed for longer term ground-control and spaceflight experiments. Ground-control and spaceflight human skin tissue samples were also processed for genomic profiling upon mission re-entry and completion. Maleth I's overall objective was achieved, as human skin tissue samples with their microbiomes travelled to space and back yielding positive results by both standard microbiology techniques and genetic typing using 16S rRNA amplicon sequencing. Preliminary findings of this mission are discussed in light of its innovative approach at DFU microbiome research, and the clinical implications that may emerge from this and other future similar studies.
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BACKGROUND: Monitoring the adaptation of microorganisms to the extreme environment of the International Space Station (ISS) is crucial to understanding microbial evolution and infection prevention. Acinetobacter pittii is an opportunistic nosocomial pathogen, primarily impacting immunocompromised patients, that was recently isolated from two missions aboard the ISS. RESULTS: Here, we report how ISS-associated A. pittii (n = 20 genomes) has formed its own genetically and functionally discrete clade distinct from most Earth-bound isolates (n = 291 genomes). The antimicrobial susceptibility testing of ISS strains and two related clinical isolates demonstrated that ISS strains acquired more resistance, specifically with regard to expanded-spectrum cephalosporins, despite no prediction of increased resistance based on genomic analysis of resistance genes. By investigating 402 longitudinal environmental and host-associated ISS metagenomes, we observed that viable A. pittii is increasing in relative abundance and therefore potentially exhibiting succession, being identified in >2X more metagenomic samples in back-to-back missions. ISS strains additionally contain functions that enable them to survive in harsh environments, including the transcriptional regulator LexA. Via a genome-wide association study, we identified a high level of mutational burden in methionine sulfoxide reductase genes relative to the most closely related Earth strains. CONCLUSIONS: Overall, these results indicated a step forward in understanding how microorganisms might evolve and alter their antibiotic resistance phenotype in extreme, resource-limited, human-built environments. Video Abstract.
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Acinetobacter , Astronave , Humanos , Estudo de Associação Genômica Ampla , Acinetobacter/genética , MetagenomaRESUMO
BACKGROUND: The gut microbiome promotes specific immune responses, and in turn, the immune system has a hand in shaping the microbiome. Cancer and autoimmune diseases are two major disease families that result from the contrasting manifestations of immune dysfunction. We hypothesized that the opposing immunological profiles between cancer and autoimmunity yield analogously inverted gut microbiome signatures. To test this, we conducted a systematic review and meta-analysis on gut microbiome signatures and their directionality in cancers and autoimmune conditions. METHODOLOGY: We searched PubMed, Web of Science, and Embase to identify relevant articles to be included in this study. The study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statements and PRISMA 2009 checklist. Study estimates were pooled by a generic inverse variance random-effects meta-analysis model. The relative abundance of microbiome features was converted to log fold change, and the standard error was calculated from the p-values, sample size, and fold change. RESULTS: We screened 3874 potentially relevant publications. A total of 82 eligible studies comprising 37 autoimmune and 45 cancer studies with 4208 healthy human controls and 5957 disease cases from 27 countries were included in this study. We identified a set of microbiome features that show consistent, opposite directionality between cancers and autoimmune diseases in multiple studies. Fusobacterium and Peptostreptococcus were the most consistently increased genera among the cancer cases which were found to be associated in a remarkable 13 (+0.5 log fold change in 5 studies) and 11 studies (+3.6 log fold change in 5 studies), respectively. Conversely, Bacteroides was the most prominent genus, which was found to be increased in 12 autoimmune studies (+0.2 log fold change in 6 studies) and decreased in six cancer studies (-0.3 log fold change in 4 studies). Sulfur-metabolism pathways were found to be the most frequent pathways among the member of cancer-increased genus and species. CONCLUSIONS: The surprising reproducibility of these associations across studies and geographies suggests a shared underlying mechanism shaping the microbiome across cancers and autoimmune diseases. Video Abstract.
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Doenças Autoimunes , Neoplasias , Humanos , Reprodutibilidade dos TestesRESUMO
Lake Hillier is a hypersaline lake known for its distinctive bright pink color. The cause of this phenomenon in other hypersaline sites has been attributed to halophiles, Dunaliella, and Salinibacter, however, a systematic analysis of the microbial communities, their functional features, and the prevalence of pigment-producing-metabolisms has not been previously studied. Through metagenomic sequencing and culture-based approaches, our results evidence that Lake Hillier is composed of a diverse set of microorganisms including archaea, bacteria, algae, and viruses. Our data indicate that the microbiome in Lake Hillier is composed of multiple pigment-producer microbes, including Dunaliella, Salinibacter, Halobacillus, Psychroflexus, Halorubrum, many of which are cataloged as polyextremophiles. Additionally, we estimated the diversity of metabolic pathways in the lake and determined that many of these are related to pigment production. We reconstructed complete or partial genomes for 21 discrete bacteria (N = 14) and archaea (N = 7), only 2 of which could be taxonomically annotated to previously observed species. Our findings provide the first metagenomic study to decipher the source of the pink color of Australia's Lake Hillier. The study of this pink hypersaline environment is evidence of a microbial consortium of pigment producers, a repertoire of polyextremophiles, a core microbiome and potentially novel species.