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1.
BMC Med Res Methodol ; 24(1): 27, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38302887

RESUMO

BACKGROUND: Standard pediatric growth curves cannot be used to impute missing height or weight measurements in individual children. The Michaelis-Menten equation, used for characterizing substrate-enzyme saturation curves, has been shown to model growth in many organisms including nonhuman vertebrates. We investigated whether this equation could be used to interpolate missing growth data in children in the first three years of life and compared this interpolation to several common interpolation methods and pediatric growth models. METHODS: We developed a modified Michaelis-Menten equation and compared expected to actual growth, first in a local birth cohort (N = 97) then in a large, outpatient, pediatric sample (N = 14,695). RESULTS: The modified Michaelis-Menten equation showed excellent fit for both infant weight (median RMSE: boys: 0.22 kg [IQR:0.19; 90% < 0.43]; girls: 0.20 kg [IQR:0.17; 90% < 0.39]) and height (median RMSE: boys: 0.93 cm [IQR:0.53; 90% < 1.0]; girls: 0.91 cm [IQR:0.50;90% < 1.0]). Growth data were modeled accurately with as few as four values from routine well-baby visits in year 1 and seven values in years 1-3; birth weight or length was essential for best fit. Interpolation with this equation had comparable (for weight) or lower (for height) mean RMSE compared to the best performing alternative models. CONCLUSIONS: A modified Michaelis-Menten equation accurately describes growth in healthy babies aged 0-36 months, allowing interpolation of missing weight and height values in individual longitudinal measurement series. The growth pattern in healthy babies in resource-rich environments mirrors an enzymatic saturation curve.


Assuntos
Cinética , Masculino , Lactente , Feminino , Humanos , Criança , Peso ao Nascer
3.
Sci Rep ; 13(1): 14045, 2023 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-37679503

RESUMO

Although chatbots such as ChatGPT can facilitate cost-effective text generation and editing, factually incorrect responses (hallucinations) limit their utility. This study evaluates one particular type of hallucination: fabricated bibliographic citations that do not represent actual scholarly works. We used ChatGPT-3.5 and ChatGPT-4 to produce short literature reviews on 42 multidisciplinary topics, compiling data on the 636 bibliographic citations (references) found in the 84 papers. We then searched multiple databases and websites to determine the prevalence of fabricated citations, to identify errors in the citations to non-fabricated papers, and to evaluate adherence to APA citation format. Within this set of documents, 55% of the GPT-3.5 citations but just 18% of the GPT-4 citations are fabricated. Likewise, 43% of the real (non-fabricated) GPT-3.5 citations but just 24% of the real GPT-4 citations include substantive citation errors. Although GPT-4 is a major improvement over GPT-3.5, problems remain.

4.
Front Sports Act Living ; 5: 1150130, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37090817

RESUMO

Introduction: Although school communities may be required to provide physical education opportunities for all students-including for those with disabilities-the same is not generally true with respect to school sport (i.e., participation in interscholastic or intramural sport programs). Hence, opportunities for inclusive school sport participation are consequently limited. Recognizing the need for continued attention and action in this area, we recently developed and piloted Game Changers-a participatory action research project. Together, 27 students with various cognitive and/or intellectual disabilities (i.e., student-participants), their schools' six physical education teachers and learning support teachers (i.e., champion-participants), four university researchers (i.e., researcher-participants), and two community partners [i.e., Physical and Health Education (PHE) Canada, Special Olympics Nova Scotia] engaged in the Game Changers project with three idealized goals: (a) to bring to the fore para/adapted/inclusive sport opportunities for all students; (b) to provide an empowering opportunity for students with disabilities to participate, make choices, and act as leaders in the development of sport programming; and (c) to engage youth with disabilities in sport as participants, leaders, mentors, and role models. Methods: Utilizing a mixed-methods design, data were collected from a variety of sources before the implementation of the Game Changers program, during its implementation, and once it was complete. These four data sources included the following: pre- and post-program survey for student-participants, pre- and post-program focus group interviews for student-participants, pre- and post-program focus group interviews for champion-participants, and school/sport observations. Results: The first cycle of this participatory action research project has yielded positive and informative findings. Strictly positive findings, among others, relate to the following: improving upon students' perceived competence and autonomy, inviting student voice, identifying and responding to sport participation barriers, and creating genuine sport opportunities within school settings. More undesirable yet informative findings, among others, relate to the following: unachieved intrinsic motivation and belonging, (un)sustainability of sport programs without "interventions" like Game Changers, recreation/leisure as "substitutes" for sport, and a continued want for authentic leadership and mentorship opportunities. Discussion: With these findings, we offer insights for future iterations of Game Changers (and programs like it) in similar school communities.

5.
J Hazard Mater ; 452: 131298, 2023 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-36996541

RESUMO

Subsea pipelines carrying well fluids from hydrocarbon fields accumulate mercury. If the pipelines (after cleaning and flushing) are abandoned in situ, their degradation may release residual mercury into the environment. To justify pipeline abandonment, decommissioning plans include environmental risk assessments to determine the potential risk of environmental mercury. These risks are informed by environmental quality guideline values (EQGVs) governing concentrations in sediment or water above which mercury toxicity may occur. However, these guidelines may not consider e.g., the bioaccumulation potential of methylated mercury. Therefore, EQGVs may not protect humans from exposure if applied as the sole basis for risk assessments. This paper outlines a process to assess the EQGVs' protectiveness from mercury bioaccumulation, providing preliminary insights to questions including how to (1) determine pipeline threshold concentrations, (2) model marine mercury bioaccumulation, and (3) determine exceedance of the methylmercury tolerable weekly intake (TWI) for humans. The approach is demonstrated with a generic example using simplifications to describe mercury behaviour and a model food web. In this example, release scenarios equivalent to the EQGVs resulted in increased marine organism mercury tissue concentrations by 0-33 %, with human dietary methylmercury intake increasing 0-21 %. This suggests that existing guidelines may not be protective of biomagnification in all circumstances. The outlined approach could inform environmental risk assessments for asset-specific release scenarios but must be parameterised to reflect local environmental conditions when tailored to local factors.


Assuntos
Mercúrio , Compostos de Metilmercúrio , Poluentes Químicos da Água , Humanos , Animais , Compostos de Metilmercúrio/metabolismo , Mercúrio/análise , Cadeia Alimentar , Bioacumulação , Organismos Aquáticos/metabolismo , Monitoramento Ambiental/métodos , Peixes/metabolismo , Poluentes Químicos da Água/análise
6.
Cell Mol Gastroenterol Hepatol ; 15(6): 1421-1442, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36828279

RESUMO

BACKGROUND & AIMS: Fiber-rich foods promote health, but mechanisms by which they do so remain poorly defined. Screening fiber types, in mice, revealed psyllium had unique ability to ameliorate 2 chronic inflammatory states, namely, metabolic syndrome and colitis. We sought to determine the mechanism of action of the latter. METHODS: Mice were fed grain-based chow, which is naturally rich in fiber or compositionally defined diets enriched with semi-purified fibers. Mice were studied basally and in models of chemical-induced and T-cell transfer colitis. RESULTS: Relative to all diets tested, mice consuming psyllium-enriched compositionally defined diets were markedly protected against both dextran sulfate sodium- and T-cell transfer-induced colitis, as revealed by clinical-type, histopathologic, morphologic, and immunologic parameters. Such protection associated with stark basal changes in the gut microbiome but was independent of fermentation and, moreover, maintained in mice harboring a minimal microbiota (ie, Altered Schaedler Flora). Transcriptomic analysis revealed psyllium induced expression of genes mediating bile acids (BA) secretion, suggesting that psyllium's known ability to bind BA might contribute to its ability to prevent colitis. As expected, psyllium resulted in elevated level of fecal BA, reflecting their removal from enterohepatic circulation but, in stark contrast to the BA sequestrant cholestyramine, increased serum BA levels. Moreover, the use of BA mimetics that activate the farnesoid X receptor (FXR), as well as the use of FXR-knockout mice, suggested that activation of FXR plays a central role in psyllium's protection against colitis. CONCLUSIONS: Psyllium protects against colitis via altering BA metabolism resulting in activation of FXR, which suppresses pro-inflammatory signaling.


Assuntos
Colite , Psyllium , Camundongos , Animais , Psyllium/efeitos adversos , Ácidos e Sais Biliares , Promoção da Saúde , Colite/induzido quimicamente , Colite/prevenção & controle , Colite/metabolismo , Inflamação , Camundongos Knockout
7.
Cell Host Microbe ; 31(2): 187-198.e3, 2023 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-36758519

RESUMO

The human gut virome and its early life development are poorly understood. Prior studies have captured single-point assessments with the evolution of the infant virome remaining largely unexplored. We performed viral metagenomic sequencing on stool samples collected longitudinally from a cohort of 53 infants from age 2 weeks to 3 years (80.7 billion reads), and from their mothers (9.8 billion reads) to examine and compare viromes. The asymptomatic infant virome consisted of bacteriophages, nonhuman dietary/environmental viruses, and human-host viruses, predominantly picornaviruses. In contrast, human-host viruses were largely absent from the maternal virome. Previously undescribed, sequence-divergent vertebrate viruses were detected in the maternal but not infant virome. As infants aged, the phage component evolved to resemble the maternal virome, but by age 3, the human-host component remained dissimilar from the maternal virome. Thus, early life virome development is determined predominantly by dietary, infectious, and environmental factors rather than direct maternal acquisition.


Assuntos
Bacteriófagos , Vírus , Feminino , Humanos , Viroma/genética , Vírus/genética , Bacteriófagos/genética , Mães , Metagenoma , Metagenômica
8.
Res Sq ; 2023 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-36711501

RESUMO

Background and Objectives: Standard pediatric growth curves cannot be used to impute missing height or weight measurements in individual children. The Michaelis-Menten equation, used for characterizing substrate-enzyme saturation curves, has been shown to model growth in many organisms including nonhuman vertebrates. We investigated this equation could be used to interpolate missing growth data in children in the first three years of life. Methods: We developed a modified Michaelis-Menten equation and compared expected to actual growth, first in a local birth cohort (N=97) then in a large, outpatient, pediatric sample (N=14,695). Results: The modified Michaelis-Menten equation showed excellent fit for both infant weight (median RMSE: boys: 0.22kg [IQR:0.19; 90%<0.43]; girls: 0.20kg [IQR:0.17; 90%<0.39]) and height (median RMSE: boys: 0.93cm [IQR:0.53; 90%<1.0]; girls: 0.91cm [IQR:0.50;90%<1.0]). Growth data were modeled accurately with as few as four values from routine well-baby visits in year 1 and seven values in years 1-3; birth weight or length was essential for best fit. Conclusions: A modified Michaelis-Menten equation accurately describes growth in healthy babies aged 0-36 months, allowing interpolation of missing weight and height values in individual longitudinal measurement series. The growth pattern in healthy babies in resource-rich environments mirrors an enzymatic saturation curve.

9.
Gut ; 72(5): 918-928, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36627187

RESUMO

OBJECTIVE: Gestational diabetes mellitus (GDM) is a condition in which women without diabetes are diagnosed with glucose intolerance during pregnancy, typically in the second or third trimester. Early diagnosis, along with a better understanding of its pathophysiology during the first trimester of pregnancy, may be effective in reducing incidence and associated short-term and long-term morbidities. DESIGN: We comprehensively profiled the gut microbiome, metabolome, inflammatory cytokines, nutrition and clinical records of 394 women during the first trimester of pregnancy, before GDM diagnosis. We then built a model that can predict GDM onset weeks before it is typically diagnosed. Further, we demonstrated the role of the microbiome in disease using faecal microbiota transplant (FMT) of first trimester samples from pregnant women across three unique cohorts. RESULTS: We found elevated levels of proinflammatory cytokines in women who later developed GDM, decreased faecal short-chain fatty acids and altered microbiome. We next confirmed that differences in GDM-associated microbial composition during the first trimester drove inflammation and insulin resistance more than 10 weeks prior to GDM diagnosis using FMT experiments. Following these observations, we used a machine learning approach to predict GDM based on first trimester clinical, microbial and inflammatory markers with high accuracy. CONCLUSION: GDM onset can be identified in the first trimester of pregnancy, earlier than currently accepted. Furthermore, the gut microbiome appears to play a role in inflammation-induced GDM pathogenesis, with interleukin-6 as a potential contributor to pathogenesis. Potential GDM markers, including microbiota, can serve as targets for early diagnostics and therapeutic intervention leading to prevention.


Assuntos
Diabetes Gestacional , Microbiota , Gravidez , Feminino , Humanos , Diabetes Gestacional/diagnóstico , Terceiro Trimestre da Gravidez , Inflamação , Citocinas
10.
Environ Sci Process Impacts ; 24(7): 1010-1025, 2022 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-35748915

RESUMO

High levels of methylmercury (MeHg) have been reported in Arctic marine biota, posing health risks to wildlife and human beings. Although MeHg concentrations of some Arctic species have been monitored for decades, the key environmental and ecological factors driving temporal trends of MeHg are largely unclear. We develop an ecosystem-based MeHg bioaccumulation model for the Beaufort Sea shelf (BSS) using the Ecotracer module of Ecopath with Ecosim, and apply the model to explore how MeHg toxicokinetics and food web trophodynamics affect bioaccumulation in the BSS food web. We show that a food web model with complex trophodynamics and relatively simple MeHg model parametrization can capture the observed biomagnification pattern of the BSS. While both benthic and pelagic production are important for transferring MeHg to fish and marine mammals, simulations suggest that benthic organisms are primarily responsible for driving the high trophic magnification factor in the BSS. We illustrate ways of combining empirical observations and modelling experiments to generate hypotheses about factors affecting food web bioaccumulation, including the MeHg elimination rate, trophodynamics, and species migration behavior. The results indicate that population dynamics rather than MeHg elimination may determine population-wide concentrations for fish and lower trophic level organisms, and cause large differences in concentrations between species at similar trophic levels. This research presents a new tool and lays the groundwork for future research to assess the pathways of global environmental changes in MeHg bioaccumulation in Arctic ecosystems in the past and the future.


Assuntos
Mercúrio , Compostos de Metilmercúrio , Poluentes Químicos da Água , Animais , Bioacumulação , Ecossistema , Monitoramento Ambiental/métodos , Peixes/metabolismo , Cadeia Alimentar , Humanos , Mamíferos/metabolismo , Compostos de Metilmercúrio/metabolismo , Poluentes Químicos da Água/análise
11.
Gastroenterology ; 162(3): 743-756, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34774538

RESUMO

BACKGROUND & AIMS: Epidemiologic and murine studies suggest that dietary emulsifiers promote development of diseases associated with microbiota dysbiosis. Although the detrimental impact of these compounds on the intestinal microbiota and intestinal health have been demonstrated in animal and in vitro models, impact of these food additives in healthy humans remains poorly characterized. METHODS: To examine this notion in humans, we performed a double-blind controlled-feeding study of the ubiquitous synthetic emulsifier carboxymethylcellulose (CMC) in which healthy adults consumed only emulsifier-free diets (n = 9) or an identical diet enriched with 15 g per day of CMC (n = 7) for 11 days. RESULTS: Relative to control subjects, CMC consumption modestly increased postprandial abdominal discomfort and perturbed gut microbiota composition in a way that reduced its diversity. Moreover, CMC-fed subjects exhibited changes in the fecal metabolome, particularly reductions in short-chain fatty acids and free amino acids. Furthermore, we identified 2 subjects consuming CMC who exhibited increased microbiota encroachment into the normally sterile inner mucus layer, a central feature of gut inflammation, as well as stark alterations in microbiota composition. CONCLUSIONS: These results support the notion that the broad use of CMC in processed foods may be contributing to increased prevalence of an array of chronic inflammatory diseases by altering the gut microbiome and metabolome (ClinicalTrials.gov, number NCT03440229).


Assuntos
Carboximetilcelulose Sódica/efeitos adversos , Dieta/efeitos adversos , Emulsificantes/efeitos adversos , Microbioma Gastrointestinal/efeitos dos fármacos , Metaboloma/efeitos dos fármacos , Animais , Método Duplo-Cego , Disbiose/etiologia , Fezes , Feminino , Voluntários Saudáveis , Humanos , Masculino , Camundongos
12.
PLoS One ; 15(8): e0236703, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32785284

RESUMO

Travelers' diarrhea (TD) is the most prevalent illness encountered by deployed military personnel and has a major impact on military operations, from reduced job performance to lost duty days. Frequently, the etiology of TD is unknown and, with underreporting of cases, it is difficult to accurately assess its impact. An increasing number of ailments include an altered or aberrant gut microbiome. To better understand the relationships between long-term deployments and TD, we studied military personnel during two nine-month deployment cycles in 2015-2016 to Honduras. To collect data on the prevalence of diarrhea and impact on duty, a total of 1173 personnel completed questionnaires at the end of their deployment. 56.7% reported reduced performance and 21.1% reported lost duty days. We conducted a passive surveillance study of all cases of diarrhea reporting to the medical unit with 152 total cases and a similar pattern of etiology. Enteroaggregative E. coli (EAEC, 52/152), enterotoxigenic E. coli (ETEC, 50/152), and enteropathogenic E. coli (EPEC, 35/152) were the most prevalent pathogens detected. An active longitudinal surveillance of 67 subjects also identified diarrheagenic E. coli as the primary etiology (7/16 EPEC, 7/16 EAEC, and 6/16 ETEC). Eleven subjects were recruited into a nested longitudinal substudy to examine gut microbiome changes associated with deployment. A 16S rRNA amplicon survey of fecal samples showed differentially abundant baseline taxa for subjects who contracted TD versus those who did not, as well as detection of taxa positively associated with self-reported gastrointestinal distress. Disrupted microbiota was also qualitatively observable for weeks preceding and following the incidents of TD. These findings illustrate the complex etiology of diarrhea amongst military personnel in deployed settings and its impacts on job performance. Potential factors of resistance or susceptibility can provide a foundation for future clinical trials to evaluate prevention and treatment strategies.


Assuntos
Diarreia/epidemiologia , Disenteria/epidemiologia , Escherichia coli Enteropatogênica/isolamento & purificação , Infecções por Escherichia coli/epidemiologia , Adulto , Diarreia/genética , Diarreia/microbiologia , Disenteria/genética , Disenteria/microbiologia , Disenteria/patologia , Escherichia coli Enteropatogênica/genética , Escherichia coli Enteropatogênica/patogenicidade , Infecções por Escherichia coli/genética , Infecções por Escherichia coli/microbiologia , Infecções por Escherichia coli/patologia , Fezes/microbiologia , Feminino , Microbioma Gastrointestinal/genética , Honduras/epidemiologia , Humanos , Masculino , Militares , RNA Ribossômico 16S/genética , Fatores de Risco , Viagem , Doença Relacionada a Viagens
13.
Nat Commun ; 10(1): 2200, 2019 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-31097702

RESUMO

Multiple factors modulate microbial community assembly in the vertebrate gut, though studies disagree as to their relative contribution. One cause may be a reliance on captive animals, which can have very different gut microbiomes compared to their wild counterparts. To resolve this disagreement, we analyze a new, large, and highly diverse animal distal gut 16 S rRNA microbiome dataset, which comprises 80% wild animals and includes members of Mammalia, Aves, Reptilia, Amphibia, and Actinopterygii. We decouple the effects of host evolutionary history and diet on gut microbiome diversity and show that each factor modulates different aspects of diversity. Moreover, we resolve particular microbial taxa associated with host phylogeny or diet and show that Mammalia have a stronger signal of cophylogeny. Finally, we find that environmental filtering and microbe-microbe interactions differ among host clades. These findings provide a robust assessment of the processes driving microbial community assembly in the vertebrate intestine.


Assuntos
Biodiversidade , Evolução Biológica , Comportamento Alimentar/fisiologia , Microbioma Gastrointestinal/genética , Vertebrados/microbiologia , Animais , Conjuntos de Dados como Assunto , Interações entre Hospedeiro e Microrganismos/fisiologia , Filogenia , RNA Ribossômico 16S/genética , RNA Ribossômico 16S/isolamento & purificação , Vertebrados/fisiologia
14.
Semin Pediatr Neurol ; 26: 50-51, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29961518

RESUMO

We present the case of a young woman with worsening attacks of muscle pain and rhabdomyolysis beginning at age 14. Initial metabolic testing and electromyography revealed findings of a nonspecific myopathy. Diagnostic options were discussed among the members of a neurogenetics clinic team. Whole-exome sequencing was selected as a first tier test. This testing revealed a known disease causing mutation in the PYGM gene consistent with McArdle disease. We discuss the decision to use whole-exome sequencing in diagnostics and the rationale for making this our choice as a first-level test modality.


Assuntos
Doença de Depósito de Glicogênio Tipo V/diagnóstico , Doença de Depósito de Glicogênio Tipo V/genética , Mialgia/diagnóstico , Mialgia/genética , Adolescente , Diagnóstico Diferencial , Feminino , Testes Genéticos , Doença de Depósito de Glicogênio Tipo V/fisiopatologia , Humanos , Mialgia/etiologia , Mialgia/fisiopatologia , Sequenciamento do Exoma
15.
Proc Natl Acad Sci U S A ; 115(28): 7368-7373, 2018 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-29941552

RESUMO

Soil microbes that colonize plant roots and are responsive to differences in plant genotype remain to be ascertained for agronomically important crops. From a very large-scale longitudinal field study of 27 maize inbred lines planted in three fields, with partial replication 5 y later, we identify root-associated microbiota exhibiting reproducible associations with plant genotype. Analysis of 4,866 samples identified 143 operational taxonomic units (OTUs) whose variation in relative abundances across the samples was significantly regulated by plant genotype, and included five of seven core OTUs present in all samples. Plant genetic effects were significant amid the large effects of plant age on the rhizosphere microbiome, regardless of the specific community of each field, and despite microbiome responses to climate events. Seasonal patterns showed that the plant root microbiome is locally seeded, changes with plant growth, and responds to weather events. However, against this background of variation, specific taxa responded to differences in host genotype. If shown to have beneficial functions, microbes may be considered candidate traits for selective breeding.


Assuntos
Endogamia , Microbiota/fisiologia , Raízes de Plantas/microbiologia , Rizosfera , Zea mays/microbiologia , Genótipo , Zea mays/genética
16.
J Environ Radioact ; 181: 118-127, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29145014

RESUMO

Ecotracer is a tool in the Ecopath with Ecosim (EwE) software package used to simulate and analyze the transport of contaminants such as methylmercury or radiocesium through aquatic food webs. Ecotracer solves the contaminant dynamic equations simultaneously with the biomass dynamic equations in Ecosim/Ecospace. In this paper, we give a detailed description of the Ecotracer module and analyze the performance on two problems of differing complexity. Ecotracer was modified from previous versions to more accurately model contaminant excretion, and new numerical integration algorithms were implemented to increase accuracy and robustness. To test the mathematical robustness of the computational algorithm, Ecotracer was tested on a simple problem for which we know an analytical solution. These results demonstrated the effectiveness of the program numerics. A much more complex model, the release of the cesium radionuclide 137Cs from the Fukushima Dai-ichi nuclear accident, was also modeled and analyzed. A comparison of the Ecotracer results to sampled 137Cs measurements in the coastal ocean area around Fukushima show the promise of the tool but also highlight some important limitations.


Assuntos
Cadeia Alimentar , Modelos Teóricos , Monitoramento de Radiação/métodos , Poluentes Radioativos da Água/análise , Contaminação Radioativa da Água/estatística & dados numéricos , Organismos Aquáticos , Radioisótopos de Césio/análise , Acidente Nuclear de Fukushima
17.
mSystems ; 2(5)2017.
Artigo em Inglês | MEDLINE | ID: mdl-29034330

RESUMO

Bisphenol A (BPA) accumulates in the maturing gut and liver in utero and is known to alter gut bacterial profiles in offspring. Gut bacterial dysbiosis may contribute to chronic colonic and systemic inflammation. We hypothesized that perinatal BPA exposure-induced intestinal (and liver) inflammation in offspring is due to alterations in the microbiome and colonic metabolome. The 16S rRNA amplicon sequencing analysis revealed differences in beta diversity with a significant reduction in the relative abundances of short-chain fatty acid (SCFA) producers such as Oscillospira and Ruminococcaceae due to BPA exposure. Furthermore, BPA exposure reduced fecal SCFA levels and increased systemic lipopolysaccharide (LPS) levels. BPA exposure-increased intestinal permeability was ameliorated by the addition of SCFA in vitro. Metabolic fingerprints revealed alterations in global metabolism and amino acid metabolism. Thus, our findings indicate that perinatal BPA exposure may cause gut bacterial dysbiosis and altered metabolite profiles, particularly SCFA profiles, leading to chronic colon and liver inflammation. IMPORTANCE Emerging evidence suggests that environmental toxicants may influence inflammation-promoted chronic disease susceptibility during early life. BPA, an environmental endocrine disruptor, can transfer across the placenta and accumulate in fetal gut and liver. However, underlying mechanisms for BPA-induced colonic and liver inflammation are not fully elucidated. In this report, we show how perinatal BPA exposure in rabbits alters gut microbiota and their metabolite profiles, which leads to colonic and liver inflammation as well as to increased gut permeability as measured by elevated serum lipopolysaccharide (LPS) levels in the offspring. Also, perinatal BPA exposure leads to reduced levels of gut bacterial diversity and bacterial metabolites (short-chain fatty acids [SCFA]) and elevated gut permeability-three common early biomarkers of inflammation-promoted chronic diseases. In addition, we showed that SCFA ameliorated BPA-induced intestinal permeability in vitro. Thus, our study results suggest that correcting environmental toxicant-induced bacterial dysbiosis early in life may reduce the risk of chronic diseases later in life.

18.
Nat Microbiol ; 2: 17004, 2017 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-28191884

RESUMO

Inflammatory bowel disease (IBD) is characterized by flares of inflammation with a periodic need for increased medication and sometimes even surgery. The aetiology of IBD is partly attributed to a deregulated immune response to gut microbiome dysbiosis. Cross-sectional studies have revealed microbial signatures for different IBD subtypes, including ulcerative colitis, colonic Crohn's disease and ileal Crohn's disease. Although IBD is dynamic, microbiome studies have primarily focused on single time points or a few individuals. Here, we dissect the long-term dynamic behaviour of the gut microbiome in IBD and differentiate this from normal variation. Microbiomes of IBD subjects fluctuate more than those of healthy individuals, based on deviation from a newly defined healthy plane (HP). Ileal Crohn's disease subjects deviated most from the HP, especially subjects with surgical resection. Intriguingly, the microbiomes of some IBD subjects periodically visited the HP then deviated away from it. Inflammation was not directly correlated with distance to the healthy plane, but there was some correlation between observed dramatic fluctuations in the gut microbiome and intensified medication due to a flare of the disease. These results will help guide therapies that will redirect the gut microbiome towards a healthy state and maintain remission in IBD.


Assuntos
Disbiose/microbiologia , Microbioma Gastrointestinal/fisiologia , Doenças Inflamatórias Intestinais/microbiologia , Adulto , Colite Ulcerativa/microbiologia , Doença de Crohn/microbiologia , Estudos Transversais , Disbiose/imunologia , Fezes/microbiologia , Feminino , Microbioma Gastrointestinal/genética , Humanos , Inflamação/microbiologia , Doenças Inflamatórias Intestinais/imunologia , Doenças Inflamatórias Intestinais/fisiopatologia , Complexo Antígeno L1 Leucocitário/análise , Masculino , Fenótipo
19.
J Mol Med (Berl) ; 95(1): 1-8, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27900395

RESUMO

Bacterial species composition in the gut has emerged as an important factor in obesity and its related metabolic diseases such as type 2 diabetes. Out of thousands of bacterial species-level phylotypes inhabiting the human gut, the majority belong to two dominant phyla, the Bacteroidetes and Firmicutes. Members of the Bacteroidetes in particular have been associated with human metabolic diseases. However, their associations with disease are not always consistent between studies. Delving deeper into the diversity within the Bacteroidetes reveals a vast diversity in genomes and capacities, which partly explain how not all members respond equally to similar environmental conditions in their hosts. Here, we discuss the Bacteroidetes phylum, associations of its members with metabolic phenotypes, and efforts to characterize functionally their interactions with their hosts. Harnessing the Bacteroidetes to promote metabolic health will require a nuanced understanding of how specific strains interact with their microbial neighbors and their hosts under various conditions.


Assuntos
Doenças Metabólicas/etiologia , Doenças Metabólicas/metabolismo , Microbiota , Animais , Bacteroidetes/fisiologia , Dieta , Microbioma Gastrointestinal , Interações Hospedeiro-Patógeno , Humanos
20.
mSystems ; 1(1)2016.
Artigo em Inglês | MEDLINE | ID: mdl-27822518

RESUMO

Designing primers for PCR-based taxonomic surveys that amplify a broad range of phylotypes in varied community samples is a difficult challenge, and the comparability of data sets amplified with varied primers requires attention. Here, we examined the performance of modified 16S rRNA gene and internal transcribed spacer (ITS) primers for archaea/bacteria and fungi, respectively, with nonaquatic samples. We moved primer bar codes to the 5' end, allowing for a range of different 3' primer pairings, such as the 515f/926r primer pair, which amplifies variable regions 4 and 5 of the 16S rRNA gene. We additionally demonstrated that modifications to the 515f/806r (variable region 4) 16S primer pair, which improves detection of Thaumarchaeota and clade SAR11 in marine samples, do not degrade performance on taxa already amplified effectively by the original primer set. Alterations to the fungal ITS primers did result in differential but overall improved performance compared to the original primers. In both cases, the improved primers should be widely adopted for amplicon studies. IMPORTANCE We continue to uncover a wealth of information connecting microbes in important ways to human and environmental ecology. As our scientific knowledge and technical abilities improve, the tools used for microbiome surveys can be modified to improve the accuracy of our techniques, ensuring that we can continue to identify groundbreaking connections between microbes and the ecosystems they populate, from ice caps to the human body. It is important to confirm that modifications to these tools do not cause new, detrimental biases that would inhibit the field rather than continue to move it forward. We therefore demonstrated that two recently modified primer pairs that target taxonomically discriminatory regions of bacterial and fungal genomic DNA do not introduce new biases when used on a variety of sample types, from soil to human skin. This confirms the utility of these primers for maintaining currently recommended microbiome research techniques as the state of the art.

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