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1.
Nat Commun ; 11(1): 4379, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32873785

RESUMO

The gut microbiome harbors a 'silent reservoir' of antibiotic resistance (AR) genes that is thought to contribute to the emergence of multidrug-resistant pathogens through horizontal gene transfer (HGT). To counteract the spread of AR, it is paramount to know which organisms harbor mobile AR genes and which organisms engage in HGT. Despite methods that characterize the overall abundance of AR genes in the gut, technological limitations of short-read sequencing have precluded linking bacterial taxa to specific mobile genetic elements (MGEs) encoding AR genes. Here, we apply Hi-C, a high-throughput, culture-independent method, to surveil the bacterial carriage of MGEs. We compare two healthy individuals with seven neutropenic patients undergoing hematopoietic stem cell transplantation, who receive multiple courses of antibiotics, and are acutely vulnerable to the threat of multidrug-resistant infections. We find distinct networks of HGT across individuals, though AR and mobile genes are associated with more diverse taxa within the neutropenic patients than the healthy subjects. Our data further suggest that HGT occurs frequently over a several-week period in both cohorts. Whereas most efforts to understand the spread of AR genes have focused on pathogenic species, our findings shed light on the role of the human gut microbiome in this process.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana/genética , Microbioma Gastrointestinal/genética , Transferência Genética Horizontal , Genes Bacterianos/efeitos dos fármacos , Adulto , Idoso , Antibacterianos/uso terapêutico , DNA Bacteriano/genética , DNA Bacteriano/isolamento & purificação , Microbioma Gastrointestinal/efeitos dos fármacos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Sequências Repetitivas Dispersas/efeitos dos fármacos , Pessoa de Meia-Idade
2.
Chemosphere ; 254: 126891, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32957291

RESUMO

Gut microbiota executes many beneficial functions. In this study, the relationship between gut microbiota and ovarian development in the swimming crab P. trituberculatus was explored for the first time. A total of 28 phyla and 422 genera were identified across all samples. However, 105 differential operational taxonomic units, and four differential phyla (Gemmatimonadetes, Actinobacteria, Firmicutes, Marinimicrobia_(SAR406_clade)) were identified. At the genus level, 42 differential genera were identified and 144 bacterial indicators were identified. A key finding was that the relative abundance of 139 indicator bacteria detected in the anisomycin-2 mg/kg group (AK group) was higher than that of blank group (BK group), control group (CK group), SP600125-15 mg/kg group (SK group). In addition, the relative abundance of three indicator bacteria (OTU_236, OTU_1395, OTU_552) detected in the SK group was higher than that of the BK, CK and AK groups. It was also found that the relative abundance of 20 differential genera (Methyloversatilis, Coprococcus_1, Erysipelotrichaceae_UCG_003, Rikenella, Corynebacterium, Ruminiclostridium, Fusicatenibacter, [Eubacterium]_ruminantium_group, Rikenellaceae_RC9_gut_group, Bifidobacterium, Lachnospiraceae_NK4A136_group, Ruminococcaceae_UCG_014, Christensenellaceae_R_7_group, uncultured_Bacteroidales_bacterium, Coprococcus_2, Desulfovibrio, Aggregatibacter, Ambiguous_taxa, Alloprevotella and Ruminococcaceae_NK4A214_group) in the SK, BK, CK, and AK group samples were increasing. These differential genera may reveal the relationship between gut microbial communities and ovarian development in P. trituberculatus after injection with the JNK pathway inhibitor SP600125 or the activator anisomycin. In summary, this study provides a new understanding into the relationship between gut microbiota and ovarian development in response to stimulation with inhibitor or activator.


Assuntos
Braquiúros/fisiologia , Microbioma Gastrointestinal/fisiologia , Animais , Bactérias/genética , Feminino , Microbioma Gastrointestinal/genética , Microbiota , RNA Ribossômico 16S/genética , Natação
3.
Ecotoxicol Environ Saf ; 203: 111041, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32888612

RESUMO

Although the production and use of PCB153 have been banned globally, PCB153 pollution remains because of its persistence and long half-life in the environment. There is ongoing evidence that exposure to PCB153 may influence gut microbiota health and increase the risk of host health. It is needed to illuminate whether there are associations between gut microbiota dysregulation and PCB153-induced host diseases. Importantly, it is urgently needed to find specific strains as biomarkers to monitor PCB153 pollution and associated disorders. The work aims to investigate the change of gut microbiota composition, structure and diversity and various host physiological indexes, to ravel the chain causality of PCB153, gut microbiota health and host health, and to find potential gut microbiota markers for PCB153 pollution. Here, adult female mice were administrated with PCB153. Obtained results indicated that PCB153 led to gut microbiota health deterioration. PCB153 exposure also induced obesity, hepatic lipid accumulation, abdominal adipose tissue depots and dyslipidemia in mice. Furthermore, specific gut microbiota significantly correlated with the host health indexes. This work provides support for the relationship between gut microbiota aberrance derived from PCB153 and risk of host health, and offers some indications of possible indicative functions of gut microbiota on PCB153 pollution.


Assuntos
Dislipidemias/induzido quimicamente , Monitoramento Ambiental/métodos , Poluentes Ambientais/toxicidade , Microbioma Gastrointestinal/efeitos dos fármacos , Obesidade/induzido quimicamente , Bifenilos Policlorados/toxicidade , Animais , Biomarcadores/análise , Colo/microbiologia , Dislipidemias/metabolismo , Dislipidemias/microbiologia , Feminino , Conteúdo Gastrointestinal/microbiologia , Microbioma Gastrointestinal/genética , Expressão Gênica/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/metabolismo , Obesidade/microbiologia , RNA Ribossômico 16S
4.
PLoS Comput Biol ; 16(9): e1008108, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32898133

RESUMO

Existing models for assessing microbiome sequencing such as operational taxonomic units (OTUs) can only test predictors' effects on OTUs. There is limited work on how to estimate the correlations between multiple OTUs and incorporate such relationship into models to evaluate longitudinal OTU measures. We propose a novel approach to estimate OTU correlations based on their taxonomic structure, and apply such correlation structure in Generalized Estimating Equations (GEE) models to estimate both predictors' effects and OTU correlations. We develop a two-part Microbiome Taxonomic Longitudinal Correlation (MTLC) model for multivariate zero-inflated OTU outcomes based on the GEE framework. In addition, longitudinal and other types of repeated OTU measures are integrated in the MTLC model. Extensive simulations have been conducted to evaluate the performance of the MTLC method. Compared with the existing methods, the MTLC method shows robust and consistent estimation, and improved statistical power for testing predictors' effects. Lastly we demonstrate our proposed method by implementing it into a real human microbiome study to evaluate the obesity on twins.


Assuntos
Biologia Computacional/métodos , DNA Bacteriano , Microbioma Gastrointestinal/genética , Modelos Estatísticos , Análise de Sequência de DNA/métodos , DNA Bacteriano/classificação , DNA Bacteriano/genética , Bases de Dados Genéticas , Humanos
5.
PLoS One ; 15(8): e0231801, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32817657

RESUMO

The cricetine rodent Peromyscus leucopus is an important reservoir for several human zoonoses, including Lyme disease, in North America. Akin to hamsters, the white-footed deermouse has been unevenly characterized in comparison to the murid Mus musculus. To further understanding of P. leucopus' total genomic content, we investigated gut microbiomes of an outbred colony of P. leucopus, inbred M. musculus, and a natural population of P. leucopus. Metagenome and whole genome sequencing were combined with microbiology and microscopy approaches. A focus was the genus Lactobacillus, four diverse species of which were isolated from forestomach and feces of colony P. leucopus. Three of the species-L. animalis, L. reuteri, and provisionally-named species "L. peromysci"-were identified in fecal metagenomes of wild P. leucopus but not discernibly in samples from M. musculus. L. johnsonii, the fourth species, was common in M. musculus but absent or sparse in wild P. leucopus. Also identified in both colony and natural populations were a Helicobacter sp. in feces but not stomach, and a Tritrichomonas sp. protozoan in cecum or feces. The gut metagenomes of colony P. leucopus were similar to those of colony M. musculus at the family or higher level and for major subsystems. But there were multiple differences between species and sexes within each species in their gut metagenomes at orthologous gene level. These findings provide a foundation for hypothesis-testing of functions of individual microbial species and for interventions, such as bait vaccines based on an autochthonous bacterium and targeting P. leucopus for transmission-blocking.


Assuntos
Microbioma Gastrointestinal/genética , Peromyscus/microbiologia , Zoonoses/microbiologia , Animais , Humanos , Lactobacillus/genética , Lactobacillus/metabolismo , Doença de Lyme/epidemiologia , Doença de Lyme/etiologia , América do Norte , Peromyscus/genética , Zoonoses/genética
6.
PLoS One ; 15(8): e0236470, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32750057

RESUMO

OBJECTIVES: Spinal cord injury (SCI) is associated with severe autonomic dysfunction. Patients with SCI often suffer from a lack of central nervous system control over the gastrointestinal system. Therefore, we hypothesized that patients with SCI would cause intestinal flora imbalance. We investigated alterations in the fecal microbiome in a group of patients with SCI. METHODS: Microbial communities in the feces of 23 patients and 23 healthy controls were investigated using high-throughput Illumina Miseq sequencing targeting the V3-V4 region of the 16S ribosomal RNA (rRNA) gene. The relative abundances between the fecal microbiota at the genus level in patients with SCI and healthy individuals were determined using cluster analysis. RESULTS: The structure and quantity of fecal microbiota differed significantly between patients with SCI and healthy controls, but the richness and diversity were not significantly different. A two-dimensional heatmap showed that the relative abundances of forty-five operational taxonomic units (OTUs) were significantly enriched either in SCI or healthy samples. Among these, 18 OTUs were more abundant in healthy controls than in patients with SCI, and 27 OTUs were more abundant in the SCI group than in healthy controls. CONCLUSION: Our study showed that patients with SCI exhibited microbiome dysbiosis.


Assuntos
Disbiose/microbiologia , Fezes/microbiologia , Microbiota/genética , Traumatismos da Medula Espinal/microbiologia , Adulto , Bactérias/classificação , Bactérias/genética , Disbiose/genética , Disbiose/patologia , Feminino , Microbioma Gastrointestinal/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Filogenia , RNA Ribossômico 16S/genética , Traumatismos da Medula Espinal/genética , Traumatismos da Medula Espinal/patologia
7.
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
8.
Nat Commun ; 11(1): 4018, 2020 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-32782301

RESUMO

The gut microbiome is an ecosystem that involves complex interactions. Currently, our knowledge about the role of the gut microbiome in health and disease relies mainly on differential microbial abundance, and little is known about the role of microbial interactions in the context of human disease. Here, we construct and compare microbial co-abundance networks using 2,379 metagenomes from four human cohorts: an inflammatory bowel disease (IBD) cohort, an obese cohort and two population-based cohorts. We find that the strengths of 38.6% of species co-abundances and 64.3% of pathway co-abundances vary significantly between cohorts, with 113 species and 1,050 pathway co-abundances showing IBD-specific effects and 281 pathway co-abundances showing obesity-specific effects. We can also replicate these IBD microbial co-abundances in longitudinal data from the IBD cohort of the integrative human microbiome (iHMP-IBD) project. Our study identifies several key species and pathways in IBD and obesity and provides evidence that altered microbial abundances in disease can influence their co-abundance relationship, which expands our current knowledge regarding microbial dysbiosis in disease.


Assuntos
Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais/microbiologia , Consórcios Microbianos , Obesidade/microbiologia , Adulto , Bactérias/crescimento & desenvolvimento , Bactérias/isolamento & purificação , Bactérias/metabolismo , Estudos de Coortes , Disbiose/metabolismo , Disbiose/microbiologia , Feminino , Microbioma Gastrointestinal/genética , Especificidade de Hospedeiro , Humanos , Doenças Inflamatórias Intestinais/metabolismo , Masculino , Redes e Vias Metabólicas , Pessoa de Meia-Idade , Obesidade/metabolismo
9.
PLoS One ; 15(8): e0237779, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32834004

RESUMO

Microbiome data consists of operational taxonomic unit (OTU) counts characterized by zero-inflation, over-dispersion, and grouping structure among samples. Currently, statistical testing methods are commonly performed to identify OTUs that are associated with a phenotype. The limitations of statistical testing methods include that the validity of p-values/q-values depend sensitively on the correctness of models and that the statistical significance does not necessarily imply predictivity. Predictive analysis using methods such as LASSO is an alternative approach for identifying associated OTUs and for measuring the predictability of the phenotype variable with OTUs and other covariate variables. We investigate three strategies of performing predictive analysis: (1) LASSO: fitting a LASSO multinomial logistic regression model to all OTU counts with specific transformation; (2) screening+GLM: screening OTUs with q-values returned by fitting a GLMM to each OTU, then fitting a GLM model using a subset of selected OTUs; (3) screening+LASSO: fitting a LASSO to a subset of OTUs selected with GLMM. We have conducted empirical studies using three simulation datasets generated using Dirichlet-multinomial models and a real gut microbiome data related to Parkinson's disease to investigate the performance of the three strategies for predictive analysis. Our simulation studies show that the predictive performance of LASSO with appropriate variable transformation works remarkably well on zero-inflated data. Our results of real data analysis show that Parkinson's disease can be predicted based on selected OTUs after the binary transformation, age, and sex with high accuracy (Error Rate = 0.199, AUC = 0.872, AUPRC = 0.912). These results provide strong evidences of the relationship between Parkinson's disease and the gut microbiome.


Assuntos
Bactérias/classificação , Interpretação Estatística de Dados , Microbioma Gastrointestinal/genética , Modelos Biológicos , Doença de Parkinson/diagnóstico , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Bactérias/genética , Bactérias/isolamento & purificação , Estudos de Coortes , Simulação por Computador , DNA Bacteriano/isolamento & purificação , Conjuntos de Dados como Assunto , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/microbiologia , Valor Preditivo dos Testes , Prognóstico , RNA Ribossômico 16S/genética , Fatores Sexuais
10.
PLoS One ; 15(7): e0236936, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32735609

RESUMO

The Roux-en-Y gastric bypass (RYGB) remains the most effective treatment for morbidly obese patients to lower body weight and improve glycemic control. There is recent evidence that the mycobiome (fungal microbiome) can aggravate disease severity in a number of diseases including inflammatory bowel disease (IBD), irritable bowel syndrome (IBS) and hepatitis; moreover, a dysbiotic fungal microbiota has been reported in the obese. We characterized fungal and bacterial microbial composition in fecal samples of 16 morbidly obese patients before and three months after RYGB surgery and compared with nine healthy controls. We found that RYGB surgery induced a clear alteration in structure and composition of the gut fungal and bacterial microbiota. Beta diversity analysis revealed significant differences in bacterial microbiota between obese patients before surgery and healthy controls (P < 0.005) and a significant, unidirectional shift in RYGB patients after surgery (P < 0.001 vs. before surgery). In contrast, there was no significant difference in fungal microbiota between groups but individually specific changes after RYGB surgery. Interestingly, RYGB surgery induced a significant reduction in fungal alpha diversity namely Chao1, Sobs, and Shannon diversity index (P<0.05, respectively) which contrasts the trend for uniform changes in bacteria towards increased richness and diversity post-surgery. We did not observe any inter-kingdom relations in RYGB patients but in the healthy control cohort and there were several correlations between fungi and bacteria and clinical parameters (P<0.05, respectively) that warrant further research. Our study identifies changes in intestinal fungal communities in RYGB patients that are distinct to changes in the bacterial microbiota.


Assuntos
Derivação Gástrica , Microbioma Gastrointestinal , Obesidade Mórbida , Adulto , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , DNA Intergênico , Fezes/microbiologia , Feminino , Fungos/classificação , Fungos/genética , Fungos/isolamento & purificação , Microbioma Gastrointestinal/genética , Microbioma Gastrointestinal/fisiologia , Genes Bacterianos , Genes Fúngicos , Humanos , Masculino , Metagenômica , Microbiota , Pessoa de Meia-Idade , Micobioma , Obesidade Mórbida/microbiologia , Obesidade Mórbida/cirurgia , Projetos Piloto , RNA Ribossômico 16S/genética
11.
PLoS One ; 15(8): e0236944, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32745090

RESUMO

Gut dysbiosis has been implicated in the pathophysiology of a growing number of non-communicable diseases. High through-put sequencing technologies and short chain fatty acid (SCFA) profiling enables surveying of the composition and function of the gut microbiota and provide key insights into host-microbiome interactions. However, a methodological problem with analyzing stool samples is that samples are treated and stored differently prior to submission for analysis potentially influencing the composition of the microbiota and its metabolites. In the present study, we simulated the sample acquisition of a large-scale study, in which stool samples were stored for up to two days in the fridge or at room temperature before being handed over to the hospital. To assess the influence of time and temperature on the microbial community and on SCFA composition in a controlled experimental setting, the stool samples of 10 individuals were exposed to room and fridge temperatures for 24 and 48 hours, respectively, and analyzed using 16S rRNA gene amplicon sequencing, qPCR and nuclear magnetic resonance spectroscopy. To best of our knowledge, this is the first study to investigate the influence of storage time and temperature on the absolute abundance of methanogens, and of Lactobacillus reuteri. The results indicate that values obtained for methanogens, L. reuteri and total bacteria are still representative even after storage for up to 48 hours at RT (20°C) or 4°C. The overall microbial composition and structure appeared to be influenced more by laboratory errors introduced during sample processing than by the actual effects of temperature and time. Although microbial activity was demonstrated by elevated SCFA at both 4°C and RT, SCFAs ratios were more stable over the different conditions and may be considered as long as samples are come from similar storage conditions.


Assuntos
Fezes/química , Fezes/microbiologia , Manejo de Espécimes/métodos , Adulto , Bactérias/genética , Disbiose/microbiologia , Ácidos Graxos Voláteis/análise , Feminino , Microbioma Gastrointestinal/genética , Humanos , Masculino , Microbiota , RNA Ribossômico 16S/genética , Temperatura , Fatores de Tempo
12.
Ecotoxicol Environ Saf ; 204: 111072, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32758694

RESUMO

Zearalenone (ZEN) is a mycotoxin that causes serious health problems in humans and animals. However, few studies have focused on the destruction of the intestinal barrier caused by ZEN. In this study, rats were exposed to different dosages of ZEN (0, 0.2, 1.0 and 5.0 mg/kg bw) by gavage for 4 weeks. The results showed that 1.0 and 5.0 mg/kg ZEN impaired gut morphology, induced the inflammatory response, reduced mucin expression, increased intestinal permeability, decreased the expression of TJ proteins and activated the RhoA/ROCK pathway. However, 0.2 mg/kg ZEN had no significant effect on intestinal barrier except for reducing the expression of some TJ proteins and mucins. Moreover, exposure to ZEN led to slight imbalance in microbiota. In conclusion, ZEN exposure resulted in intestinal barrier dysfunction by inducing intestinal microbiota dysbiosis, decreasing the expression of TJ proteins, activating the RhoA/ROCK pathway, and inducing the inflammatory response.


Assuntos
Microbioma Gastrointestinal/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Jejuno/efeitos dos fármacos , Zearalenona/toxicidade , Animais , Relação Dose-Resposta a Droga , Disbiose/induzido quimicamente , Feminino , Microbioma Gastrointestinal/genética , Humanos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Mucosa Intestinal/patologia , Jejuno/microbiologia , Jejuno/patologia , Masculino , Mucinas/metabolismo , Permeabilidade , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Quinases Associadas a rho/metabolismo , Proteína rhoA de Ligação ao GTP/metabolismo
14.
PLoS One ; 15(7): e0234005, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32609768

RESUMO

Rhipicephalus microplus is recognized as a tick species highly prevalent in cattle, with a wide pantropical distribution that seems to continue spreading geographically. However, its role as a biological vector has been scarcely studied in the livestock context. In this study, a 16S rRNA next-generation sequencing analysis was used to determine bacterial diversity in salivary glands and gut of R. microplus from two contrasting livestock agroecosystems in Antioquia, Colombia. Both the culture-independent approach (CI) and the culture-dependent (CD) approach were complementarily adopted in this study. A total of 341 unique OTUs were assigned, the richness showed to be higher in the Northern than in the Middle Magdalena region, and a high diversity was found at the phylum and genus levels in the samples obtained. With the CI approach, Proteobacteria, Bacteroidetes, Firmicutes, and Actinobacteria were the most common phylum of bacteria regardless of the organ, or geographic origin of the specimens analyzed. While the relative abundance of bacteria at a phylum level with the CD approach varied between analyzed samples, the data obtained suggest that a high diversity of species of bacteria occurs in R. microplus from both livestock agroecosystems. Bacterial genera such as Anaplasma, Coxiella, and Ehrlichia, recognized for their implications in tick-borne diseases, were also detected, together with endosymbionts such as Lysinibacillus, previously reported as a potential tool for biological control. This information is useful to deepen the knowledge about microbial diversity regarding the relations between endosymbionts and pathogens and could facilitate the future development of epidemiological surveillance in livestock systems.


Assuntos
Bactérias/classificação , Rhipicephalus/genética , Rhipicephalus/microbiologia , Animais , Bactérias/genética , Bovinos , Doenças dos Bovinos/microbiologia , Colômbia , Microbioma Gastrointestinal/genética , Gado/genética , RNA Ribossômico 16S/genética , Saliva/química , Infestações por Carrapato/veterinária , Doenças Transmitidas por Carrapatos/epidemiologia
15.
Nat Med ; 26(7): 1089-1095, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32632193

RESUMO

Modern lifestyles increase the risk of chronic diseases, in part by modifying the microbiome, but the health effects of lifestyles enforced on ethnic minorities are understudied1-3. Lifestyle affects the microbiome early in life, when the microbiome is assembled and the immune system is undergoing maturation4-6. Moreover, the influence of lifestyle has been separated from genetic and geographic factors by studies of genetically similar populations and ethnically distinct groups living in the same geographic location7-11. The lifestyle of Irish Travellers, an ethnically distinct subpopulation, changed with legislation in 2002 that effectively ended nomadism and altered their living conditions. Comparative metagenomics of gut microbiomes shows that Irish Travellers retain a microbiota similar to that of non-industrialized societies. Their microbiota is associated with non-dietary factors and is proportionately linked with risk of microbiome-related metabolic disease. Our findings suggest there are microbiome-related public health implications when ethnic minorities are pressured to change lifestyles.


Assuntos
Doença Crônica/epidemiologia , Microbioma Gastrointestinal/genética , Sistema Imunitário/imunologia , Estilo de Vida , Adulto , Grupos Étnicos/genética , Fezes/microbiologia , Microbioma Gastrointestinal/imunologia , Genética Populacional , Humanos , Sistema Imunitário/microbiologia , Irlanda/epidemiologia , Masculino , Metagenômica/métodos , Microbiota/genética , Microbiota/imunologia , Filogenia , Roma/genética , Migrantes
16.
PLoS One ; 15(6): e0229699, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32525954

RESUMO

BACKGROUND: Antibiotic use for livestock is presumed to be a contributor to the acquisition of antimicrobial resistance (AMR) genes in humans, yet studies do not capture AMR data before and after livestock introduction. METHODS: We performed a feasibility study by recruiting a subset of women in a delayed-start randomized controlled trial of small-scale chicken farming to examine the prevalence of clinically-relevant AMR genes. Stool samples were obtained at baseline and one year post-randomization from five intervention women who received chickens at the start of the study, six control women who did not receive chickens until the end of the study, and from chickens provided to the control group at the end of the study. Stool was screened for 87 clinically significant AMR genes using a commercially available qPCR array (Qiagen). RESULTS: Chickens harbored 23 AMR genes from classes found in humans as well as additional vancomycin and ß-lactamase resistance genes. AMR patterns between intervention and control women appeared more similar at baseline than one year post randomization (PERMANOVA R2 = 0.081, p = 0.61 at baseline, R2 = 0.186, p = 0.09 at 12 months) Women in the control group who had direct contact with the chickens sampled in the study had greater similarities in AMR gene patterns to chickens than those in the intervention group who did not have direct contact with chickens sampled (p = 0.01). However, at one year there was a trend towards increased similarity in AMR patterns between humans in both groups and the chickens sampled (p = 0.06). CONCLUSIONS: Studies designed to evaluate human AMR genes in the setting of animal exposure should account for high baseline AMR rates. Concomitant collection of animal, human, and environmental samples over time is recommended to determine the directionality and source of AMR genes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT02619227.


Assuntos
Galinhas/microbiologia , Farmacorresistência Bacteriana/genética , Fazendas , Microbioma Gastrointestinal/genética , População Rural/estatística & dados numéricos , Adulto , Animais , Estudos de Viabilidade , Feminino , Humanos , Exposição Ocupacional/efeitos adversos , Uganda
17.
BMC Bioinformatics ; 21(1): 225, 2020 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-32493208

RESUMO

BACKGROUND: Advances in DNA sequencing have offered researchers an unprecedented opportunity to better study the variety of species living in and on the human body. However, the analysis of microbiome data is complicated by several challenges. First, the sequencing depth may vary by orders of magnitude across samples. Second, species are rare and the data often contain many zeros. Third, the specimen is a fraction of the microbial ecosystem, and so the data are compositional carrying only relative information. Other characteristics of microbiome data include pronounced over-dispersion in taxon abundances, and the existence of a phylogenetic tree that relates all bacterial species. To address some of these challenges, microbiome analysis workflows often normalize the read counts prior to downstream analysis. However, there are limitations in the current literature on the normalization of microbiome data. RESULTS: Under the multinomial distribution for the read counts and a prior for the unknown proportions, we propose an empirical Bayes approach to microbiome data normalization. Using a tree-based extension of the Dirichlet prior, we further extend our method by incorporating the phylogenetic tree into the normalization process. We study the impact of normalization on differential abundance analysis. In the presence of tree structure, we propose a phylogeny-aware detection procedure. CONCLUSIONS: Extensive simulations and gut microbiome data applications are conducted to demonstrate the superior performance of our empirical Bayes method over other normalization methods, and over commonly-used methods for differential abundance testing. Original R scripts are available at GitHub (https://github.com/liudoubletian/eBay).


Assuntos
Microbiota , Algoritmos , Bactérias/genética , Sequência de Bases , Teorema de Bayes , Índice de Massa Corporal , Criança , Simulação por Computador , Microbioma Gastrointestinal/genética , Humanos , Obesidade/microbiologia , Filogenia
18.
PLoS One ; 15(6): e0234046, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32585680

RESUMO

The recent ban of the antimicrobial compound triclosan from use in consumer soaps followed research that showcased the risk it poses to the environment and to human health. Triclosan has been found in human plasma, urine and milk, demonstrating that it is present in human tissues. Previous work has also demonstrated that consumption of triclosan disrupts the gut microbial community of mice and zebrafish. Due to the widespread use of triclosan and ubiquity in the environment, it is imperative to understand the impact this chemical has on the human body and its symbiotic resident microbes. To that end, this study is the first to explore how triclosan impacts the human gut microbial community in vitro both during and after treatment. Through our in vitro system simulating three regions of the human gut; the ascending colon, transverse colon, and descending colon regions, we found that treatment with triclosan significantly impacted the community structure in terms of reduced population, diversity, and metabolite production, most notably in the ascending colon region. Given a 2 week recovery period, most of the population levels, community structure, and diversity levels were recovered for all colon regions. Our results demonstrate that the human gut microbial community diversity and population size is significantly impacted by triclosan at a high dose in vitro, and that the community is recoverable within this system.


Assuntos
Microbioma Gastrointestinal/efeitos dos fármacos , Triclosan/farmacologia , Biodiversidade , Relação Dose-Resposta a Droga , Microbioma Gastrointestinal/genética , Humanos
19.
Chemosphere ; 258: 127067, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32544817

RESUMO

Dichloroacetonitrile (DCAN) is one of the emerging nitrogenous disinfection by-products (DBPs) in drinking water. However, its potential toxicological effects remain poorly understood, especially at a low concentration found in the environment. In the present study, we investigated whether the consumption of low-concentration DCAN through drinking water would produce significant effects in male SD rats, with particular focus on their physiological traits and changes in their gut microbiome and metabolite profiles. After a 4-weeks DCAN intervention, significant changes were observed in the body weight, blood indices, and histology in DCAN-treated (100 µg/L) group. Proteobacteria was relatively less abundant in 20 and 100 µg/L DCAN-treated groups compared with that in the control group at phylum level. At genus level, Parasutterella and Anaerotruncus were significantly less abundant in both 20 and 100 µg/L DCAN-treated groups than that in the control group. Furthermore, the gut microbiota-related metabolites were dramatically perturbed after DCAN consumption. In the 20 and 100 µg/L DCAN-treated groups, there were 48 and 95 altered metabolites, respectively, and were found to be involved in sphingolipid signaling pathway, fatty acid biosynthesis, and cGMP-PKG signaling pathway. In summary, we demonstrated that consumption of low-concentration DCAN through drinking water could impair host health and induce gut microbiota dysbiosis and gut microflora-related metabolic disorders in male SD rats. Our findings highlight the potential toxicity of low-concentration DBPs and provide new insight into potential causal relationship between low concentration DBPs found in the drinking water and the host health.


Assuntos
Acetonitrilos/toxicidade , Água Potável , Microbioma Gastrointestinal/efeitos dos fármacos , Metaboloma/efeitos dos fármacos , Purificação da Água/métodos , Animais , Análise Química do Sangue , Desinfecção/métodos , Água Potável/efeitos adversos , Água Potável/química , Disbiose/induzido quimicamente , Ácidos Graxos/metabolismo , Microbioma Gastrointestinal/genética , Masculino , Ratos Sprague-Dawley , Esfingolipídeos/metabolismo
20.
Nature ; 582(7813): 566-570, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32555455

RESUMO

The gut microbiota synthesize hundreds of molecules, many of which influence host physiology. Among the most abundant metabolites are the secondary bile acids deoxycholic acid (DCA) and lithocholic acid (LCA), which accumulate at concentrations of around 500 µM and are known to block the growth of Clostridium difficile1, promote hepatocellular carcinoma2 and modulate host metabolism via the G-protein-coupled receptor TGR5 (ref. 3). More broadly, DCA, LCA and their derivatives are major components of the recirculating pool of bile acids4; the size and composition of this pool are a target of therapies for primary biliary cholangitis and nonalcoholic steatohepatitis. Nonetheless, despite the clear impact of DCA and LCA on host physiology, an incomplete knowledge of their biosynthetic genes and a lack of genetic tools to enable modification of their native microbial producers limit our ability to modulate secondary bile acid levels in the host. Here we complete the pathway to DCA and LCA by assigning and characterizing enzymes for each of the steps in its reductive arm, revealing a strategy in which the A-B rings of the steroid core are transiently converted into an electron acceptor for two reductive steps carried out by Fe-S flavoenzymes. Using anaerobic in vitro reconstitution, we establish that a set of six enzymes is necessary and sufficient for the eight-step conversion of cholic acid to DCA. We then engineer the pathway into Clostridium sporogenes, conferring production of DCA and LCA on a nonproducing commensal and demonstrating that a microbiome-derived pathway can be expressed and controlled heterologously. These data establish a complete pathway to two central components of the bile acid pool.


Assuntos
Ácidos e Sais Biliares/química , Ácidos e Sais Biliares/metabolismo , Microbioma Gastrointestinal/genética , Microbioma Gastrointestinal/fisiologia , Hidroxilação/genética , Redes e Vias Metabólicas/genética , Animais , Clostridium/enzimologia , Clostridium/genética , Clostridium/metabolismo , Ácido Desoxicólico/química , Ácido Desoxicólico/metabolismo , Ácido Litocólico/química , Ácido Litocólico/metabolismo , Masculino , Engenharia Metabólica , Camundongos , Óperon/genética , Simbiose
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