Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 40
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
FEBS Open Bio ; 2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31622538

RESUMO

Fecal microbiota transplantation (FMT), which is thought to have the potential to correct dysbiosis of gut microbiota, has been used to treat inflammatory bowel disease (IBD) for almost a decade. Here, we report an interventional prospective cohort study performed to elucidate the extent of and processes underlying microbiota engraftment in IBD patients after FMT treatment. The cohort included two categories of patients: (1) patients with moderate to severe Crohn's disease (CD)(Harvey-Bradshaw Index ≥ 7, n = 11) and (2) patients with ulcerative colitis (UC) (Montreal classification S2 and S3, n = 4). All patients were treated with a single FMT (via mid-gut, from healthy donors) and follow-up visits were performed at baseline, 3 days, one week, and one month after FMT (missing time points included). At each follow-up time point, fecal samples and clinical metadata were collected. For comparative analysis, 10 fecal samples from 10 healthy donors were included to represent the diversity level of normal gut microbiota. Additionally, the metagenomic data of 25 fecal samples from 5 individuals with metabolic syndrome who underwent autologous FMT treatment were downloaded from a previous published paper to represent fluctuations in microbiota induced during FMT. All fecal samples underwent shotgun metagenomic sequencing. We found that 3 days after FMT, 11 out of 15 recipients were in remission (3 out of 4 UC recipients; 8 out of 11 CD recipients). Generally, bacterial colonization was observed to be lower in CD recipients than in UC recipients at both species and strain levels. Furthermore, across species, different strains displayed disease-specific displacement advantages under two-disease status. Finally, most post-FMT species (> 80%) could be properly predicted (AUC > 85%) using a random forest classification model, with the gut microbiota composition and clinical parameters of pre-FMT recipients acting as factors that contribute to prediction accuracy.

2.
EBioMedicine ; 47: 373-383, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31492563

RESUMO

BACKGROUND: The gut microbiota plays important roles in modulating host metabolism. Previous studies have demonstrated differences in the gut microbiome of T2D and prediabetic individuals compared to healthy individuals, with distinct disease-related microbial profiles being reported in groups of different age and ethnicity. However, confounding factors such as anti-diabetic medication hamper identification of the gut microbial changes in disease development. METHOD: We used a combination of in-depth metagenomics and metaproteomics analyses of faecal samples from treatment-naïve type 2 diabetic (TN-T2D, n = 77), pre-diabetic (Pre-DM, n = 80), and normal glucose tolerant (NGT, n = 97) individuals to investigate compositional and functional changes of the gut microbiota and the faecal content of microbial and host proteins in Pre-DM and treatment-naïve T2D individuals to elucidate possible host-microbial interplays characterizing different disease stages. FINDINGS: We observed distinct differences characterizing the gut microbiota of these three groups and validated several key features in an independent TN-T2D cohort. We also demonstrated that the content of several human antimicrobial peptides and pancreatic enzymes differed in faecal samples between three groups. INTERPRETATION: Our findings suggest a complex, disease stage-dependent interplay between the gut microbiota and the host and point to the value of metaproteomics to gain further insight into interplays between the gut microbiota and the host. FUND: The study was supported by the National Natural Science Foundation of China (No. 31601073), the National Key Research and Development Program of China (No. 2017YFC0909703) and the Shenzhen Municipal Government of China (No. JCYJ20170817145809215). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

3.
Mol Psychiatry ; 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31391545

RESUMO

Accumulating evidence suggests that gut microbiota plays a role in the pathogenesis of schizophrenia via the microbiota-gut-brain axis. This study sought to investigate whether transplantation of fecal microbiota from drug-free patients with schizophrenia into specific pathogen-free mice could cause schizophrenia-like behavioral abnormalities. The results revealed that transplantation of fecal microbiota from schizophrenic patients into antibiotic-treated mice caused behavioral abnormalities such as psychomotor hyperactivity, impaired learning and memory in the recipient animals. These mice also showed elevation of the kynurenine-kynurenic acid pathway of tryptophan degradation in both periphery and brain, as well as increased basal extracellular dopamine in prefrontal cortex and 5-hydroxytryptamine in hippocampus, compared with their counterparts receiving feces from healthy controls. Furthermore, colonic luminal filtrates from the mice transplanted with patients' fecal microbiota increased both kynurenic acid synthesis and kynurenine aminotransferase II activity in cultured hepatocytes and forebrain cortical slices. Sixty species of donor-derived bacteria showed significant difference between the mice colonized with the patients' and the controls' fecal microbiota, highlighting 78 differentially enriched functional modules including tryptophan biosynthesis function. In conclusion, our study suggests that the abnormalities in the composition of gut microbiota contribute to the pathogenesis of schizophrenia partially through the manipulation of tryptophan-kynurenine metabolism.

4.
Microbiome ; 7(1): 107, 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31315667

RESUMO

BACKGROUND: Early treatment is key for optimizing the therapeutic success of drugs, and the current initiating treatment that blocks the progression of bone destruction during the pre-arthritic stages remains unsatisfactory. The microbial disorder in rheumatoid arthritis (RA) patients is significantly reversed with effective treatment. Modulating aberrant gut microbiomes into a healthy state is a potential therapeutic approach for preventing bone damage. RESULTS: By using metagenomic shotgun sequencing and a metagenome-wide association study, we assessed the effect of Lactobacillus casei (L. casei) on the induction of arthritis as well as on the associated gut microbiota and immune disorders in adjuvant-induced arthritis (AIA) rats. Treatment of AIA rats with L. casei inhibited joint swelling, lowered arthritis scores, and prevented bone destruction. Along with the relief of arthritis symptoms, dysbiosis in the microbiome of arthritic rats was significantly reduced after L. casei intervention. The relative abundance of AIA-decreased Lactobacillus strains, including Lactobacillus hominis, Lactobacillus reuteri, and Lactobacillus vaginalis, were restored to normal and Lactobacillus acidophilus was upregulated by the administration of L. casei to the AIA rats. Moreover, L. casei downregulated the expression of pro-inflammatory cytokines, which are closely linked to the effect of the L. casei treatment-associated microbes. Functionally, the maintenance of the redox balance of oxidative stress was involved in the improvement in the L. casei-treated AIA rats. CONCLUSION: A single bacterium, L. casei (ATCC334), was able to significantly suppress the induction of AIA and protect bones from destruction in AIA rats by restoring the microbiome dysbiosis in the gut, indicating that using probiotics may be a promising strategy for treating RA, especially in the early stage of the disease.

5.
Ann Rheum Dis ; 78(6): 773-780, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30936065

RESUMO

OBJECTIVE: The strong genetic contribution of the major histocompatibility complex (MHC) region to rheumatoid arthritis (RA) has been generally attributed to human leukocyte antigen (HLA)-DRB1. However, due to the high polymorphisms and linkage disequilibrium within MHC, it is difficult to define novel and/or independent genetic risks using conventional HLA genotyping or chip-based microarray technology. This study aimed to identify novel RA risk variants by performing deep sequencing for MHC. METHODS: We first conducted target sequencing for the entire MHC region in 357 anticitrullinated protein antibodies (ACPA)-positive patients with RA and 1001 healthy controls, and then performed HLA typing in an independent case-control cohort consisting of 1415 samples for validation. All study subjects were Han Chinese. Genetic associations for RA susceptibility and severity were analysed. Comparative modelling was constructed to predict potential functions for the newly discovered RA association variants. RESULTS: HLA-DQα1:160D conferred the strongest and independent susceptibility to ACPA-positive RA (p=6.16×10-36, OR=2.29). DRß1:37N had an independent protective effect (p=5.81×10-16, OR=0.49). As predicted by comparative modelling, the negatively charged DQα1:160D stabilises the dimer of dimers, thus may lead to an increased T cell activation. The negatively charged DRß1:37N encoding alleles preferentially bind with epitope P9 arginine, thus may result in a decreased RA susceptibility. CONCLUSIONS: We provide the first evidence that HLA-DQα1:160D, instead of HLA-DRB1*0405, is the strongest and independent genetic risk for ACPA-positive RA in Han Chinese. Our study also illustrates the value of deep sequencing for fine-mapping disease risk variants in the MHC region.

6.
Nat Biotechnol ; 37(2): 179-185, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30718868

RESUMO

Reference genomes are essential for metagenomic analyses and functional characterization of the human gut microbiota. We present the Culturable Genome Reference (CGR), a collection of 1,520 nonredundant, high-quality draft genomes generated from >6,000 bacteria cultivated from fecal samples of healthy humans. Of the 1,520 genomes, which were chosen to cover all major bacterial phyla and genera in the human gut, 264 are not represented in existing reference genome catalogs. We show that this increase in the number of reference bacterial genomes improves the rate of mapping metagenomic sequencing reads from 50% to >70%, enabling higher-resolution descriptions of the human gut microbiome. We use the CGR genomes to annotate functions of 338 bacterial species, showing the utility of this resource for functional studies. We also carry out a pan-genome analysis of 38 important human gut species, which reveals the diversity and specificity of functional enrichment between their core and dispensable genomes.


Assuntos
Biologia Computacional/métodos , Microbioma Gastrointestinal , Metagenoma , Bactérias/classificação , Análise por Conglomerados , Sequência Conservada , Fezes , Genoma Bacteriano , Genômica , Humanos , Metagenômica , Filogenia , Polimorfismo de Nucleotídeo Único , RNA Ribossômico 16S/genética , Análise de Sequência de DNA
8.
Methods Enzymol ; 610: 59-72, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30390805

RESUMO

The human microbiome is our "other genome." Implicated in a growing list of complex diseases, for which genomic studies typically explain a portion of the disease susceptibility, the human gut microbiome has been at the spotlight for our understanding of human diseases. As the microbiome is intrinsically more variable than the human genome, it is important to take careful considerations at each step of a study. Here, we put forward our recommendations, which we envision would facilitate identification of true drug targets in the human microbiome in the colon as well as at other body sites.

10.
Gigascience ; 7(11)2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-30277499

RESUMO

Pangenome analyses facilitate the interpretation of genetic diversity and evolutionary history of a taxon. However, there is an urgent and unmet need to develop new tools for advanced pangenome construction and visualization, especially for metagenomic data. Here, we present an integrated pipeline, named MetaPGN, for construction and graphical visualization of pangenome networks from either microbial genomes or metagenomes. Given either isolated genomes or metagenomic assemblies coupled with a reference genome of the targeted taxon, MetaPGN generates a pangenome in a topological network, consisting of genes (nodes) and gene-gene genomic adjacencies (edges) of which biological information can be easily updated and retrieved. MetaPGN also includes a self-developed Cytoscape plugin for layout of and interaction with the resulting pangenome network, providing an intuitive and interactive interface for full exploration of genetic diversity. We demonstrate the utility of MetaPGN by constructing Escherichia coli pangenome networks from five E. coli pathogenic strains and 760 human gut microbiomes,revealing extensive genetic diversity of E. coli within both isolates and gut microbial populations. With the ability to extract and visualize gene contents and gene-gene physical adjacencies of a specific taxon from large-scale metagenomic data, MetaPGN provides advantages in expanding pangenome analysis to uncultured microbial taxa.

11.
BMC Microbiol ; 18(1): 114, 2018 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-30208875

RESUMO

BACKGROUND: Asthma, one of the most common chronic respiratory disorders, is associated with the hyper-activation of the T-cell subset of adaptive immunity. The gut microbiota may be involved in the development of asthma through the production of short-chain fatty acids (SCFAs), exhibiting modulatory effects on Th. So, we performed a metagenome-wide association study (MWAS) of the fecal microbiota from individuals with asthma and healthy controls. And that was the first case to resolve the relationship between asthma and microbiome among UK adults. RESULTS: The microbiota of the individuals with asthma consisted of fewer microbial entities than the microbiota of healthy individuals. Faecalibacterium prausnitzii, Sutterella wadsworthensis and Bacteroides stercoris were depleted in cases, whereas Clostridiums with Eggerthella lenta were over-represented in individuals with asthma. Functional analysis shows that the SCFAs might be altered in the microbiota of asthma patients. CONCLUSION: In all, the adult human gut microbiome of asthma patients is clearly different from healthy controls. The functional and taxa results showed that the change of asthma patients might related to SCFAs.

12.
Gigascience ; 7(10)2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-30192933

RESUMO

Background: The human uterus is traditionally believed to be sterile, while the vaginal microbiota plays an important role in fending off pathogens. Emerging evidence demonstrates the presence of bacteria beyond the vagina. However, a microbiome-wide metagenomic analysis characterizing the diverse microbial communities has been lacking. Results: We performed shotgun-sequencing of 52 samples from the cervical canal and the peritoneal fluid of Chinese women of reproductive age using the Illumina platform. Direct annotation of sequencing reads identified the taxonomy of bacteria, archaea, fungi and viruses, confirming and extending the results from our previous study. We replicated our previous findings in another 24 samples from the vagina, the cervical canal, the uterus and the peritoneal fluid using the BGISEQ-500 platform revealing that microorganisms in the samples from the same individuals were largely shared in the entire reproductive tract. Human sequences made up more than 99% of the 20GB raw data. After filtering, vaginal microorganisms were well covered in the generated reproductive tract gene catalogue, while the more diverse upper reproductive tract microbiota would require greater depth of sequencing and more samples to meet the full coverage scale. Conclusions: We provide novel detailed data on the microbial composition of a largely unchartered body site, the female reproductive tract. Our results indicated the presence of an intra-individual continuum of microorganisms that gradually changed from the vagina to the peritoneal fluid. This study also provides a framework for understanding the implications of the composition and functional potential of the distinct microbial ecosystems of the female reproductive tract in relation to health and disease.

13.
Gigascience ; 7(9)2018 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-30137359

RESUMO

Macaca fascicularis, the cynomolgus macaque, is a widely used model in biomedical research and drug development as its genetics and physiology are close to those of humans. Detailed information on the cynomolgus macaque gut microbiota, the functional interplay between the gut microbiota and host physiology, and possible similarities to humans and other mammalians is very limited. The aim of this study was to construct the first cynomolgus macaque gut microbial gene catalog and compare this catalog to the human, pig, and mouse gut microbial gene catalogs. We performed metagenomic sequencing on fecal samples from 20 cynomolgus macaques and identified 1.9 million non-redundant bacterial genes of which 39.49% and 25.45% are present in the human and pig gut bacterial gene catalogs, respectively, whereas only 0.6% of the genes are present in the mouse gut bacterial gene catalog. By contrast, at the functional levels, more than 76% Kyoto Encyclopedia of Genes and Genomes orthologies are shared between the gut microbiota of all four mammalians. Thirty-two highly abundant bacterial genera could be defined as core genera of these mammalians. We demonstrated significant differences in the composition and functional potential of the gut microbiota as well as in the distribution of predicted bacterial phage sequences in cynomolgus macaques fed either a low-fat/high-fiber diet or a high-fat/low-fiber diet. Interestingly, the gut microbiota of cynomolgus macaques fed the high-fat/low-fiber diet became more similar to the gut microbiota of humans.

14.
Gigascience ; 7(5)2018 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-29762673

RESUMO

Background: Laboratory rats such as the Sprague-Dawley (SD) rats are an important model for biomedical studies in relation to human physiological or pathogenic processes. Here we report the first catalog of microbial genes in fecal samples from Sprague-Dawley rats. Findings: The catalog was established using 98 fecal samples from 49 SD rats, divided in 7 experimental groups, and collected at different time points 30 days apart. The established gene catalog comprises 5,130,167 non-redundant genes with an average length of 750 bp, among which 64.6% and 26.7% were annotated to phylum and genus levels, respectively. Functionally, 53.1%, 21.8%,and 31% of the genes could be annotated to KEGG orthologous groups, modules, and pathways, respectively. Conclusions: A comparison of rat gut metagenome catalogue with human or mouse revealed a higher pairwise overlap between rats and humans (2.47%) than between mice and humans (1.19%) at the gene level. Ninety-seven percent of the functional pathways in the human catalog were present in the rat catalogue, underscoring the potential use of rats for biomedical research.


Assuntos
Trato Gastrointestinal/metabolismo , Metagenoma/genética , Animais , Fezes/microbiologia , Microbioma Gastrointestinal/genética , Humanos , Masculino , Camundongos , Anotação de Sequência Molecular , Ratos Sprague-Dawley
15.
Microbiome ; 6(1): 43, 2018 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-29482661

RESUMO

BACKGROUND: The number of large-scale studies on the gut microbiota in human cohorts is rapidly increasing. However, the few and expensive options for storage of fecal samples at room temperature have been an obstacle for large-scale metagenomic studies and the development of clinical/commercial personal metagenomic sequencing. RESULTS: In this study, we systematically tested a novel N-octylpyridinium bromide-based fecal sample preservation method and compared it with other currently used storage methods. We found that the N-octylpyridinium bromide-based method enabled preservation of the bacterial composition in fecal samples transported and stored at room temperature for up to at least 14 days. CONCLUSIONS: We describe a novel chemical stabilizer that allows cost-effective transportation and storage at room temperature for several days with preservation of bacterial composition. This method will facilitate sample collection even in remote area and also enable transport via normal commercial transportation routes.

16.
Nat Commun ; 8(1): 875, 2017 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-29042534

RESUMO

Reports on bacteria detected in maternal fluids during pregnancy are typically associated with adverse consequences, and whether the female reproductive tract harbours distinct microbial communities beyond the vagina has been a matter of debate. Here we systematically sample the microbiota within the female reproductive tract in 110 women of reproductive age, and examine the nature of colonisation by 16S rRNA gene amplicon sequencing and cultivation. We find distinct microbial communities in cervical canal, uterus, fallopian tubes and peritoneal fluid, differing from that of the vagina. The results reflect a microbiota continuum along the female reproductive tract, indicative of a non-sterile environment. We also identify microbial taxa and potential functions that correlate with the menstrual cycle or are over-represented in subjects with adenomyosis or infertility due to endometriosis. The study provides insight into the nature of the vagino-uterine microbiome, and suggests that surveying the vaginal or cervical microbiota might be useful for detection of common diseases in the upper reproductive tract.Whether the female reproductive tract harbours distinct microbiomes beyond the vagina has been a matter of debate. Here, the authors show a subject-specific continuity in microbial communities at six sites along the female reproductive tract, indicative of a non-sterile environment.


Assuntos
Tubas Uterinas/microbiologia , Microbiota/fisiologia , Útero/microbiologia , Vagina/microbiologia , Adenomiose/complicações , Adenomiose/microbiologia , Adulto , Bactérias/classificação , Bactérias/genética , Endometriose/complicações , Endometriose/microbiologia , Feminino , Humanos , Infertilidade Feminina/complicações , Infertilidade Feminina/microbiologia , Ciclo Menstrual , Microbiota/genética , RNA Ribossômico 16S/genética , Adulto Jovem
17.
Nat Commun ; 8(1): 845, 2017 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-29018189

RESUMO

The gut microbiota has been linked to cardiovascular diseases. However, the composition and functional capacity of the gut microbiome in relation to cardiovascular diseases have not been systematically examined. Here, we perform a metagenome-wide association study on stools from 218 individuals with atherosclerotic cardiovascular disease (ACVD) and 187 healthy controls. The ACVD gut microbiome deviates from the healthy status by increased abundance of Enterobacteriaceae and Streptococcus spp. and, functionally, in the potential for metabolism or transport of several molecules important for cardiovascular health. Although drug treatment represents a confounding factor, ACVD status, and not current drug use, is the major distinguishing feature in this cohort. We identify common themes by comparison with gut microbiome data associated with other cardiometabolic diseases (obesity and type 2 diabetes), with liver cirrhosis, and rheumatoid arthritis. Our data represent a comprehensive resource for further investigations on the role of the gut microbiome in promoting or preventing ACVD as well as other related diseases.The gut microbiota may play a role in cardiovascular diseases. Here, the authors perform a metagenome-wide association study on stools from individuals with atherosclerotic cardiovascular disease and healthy controls, identifying microbial strains and functions associated with the disease.


Assuntos
Aterosclerose/microbiologia , Microbioma Gastrointestinal , Metagenoma , Estudos de Casos e Controles , Fermentação , Microbioma Gastrointestinal/efeitos dos fármacos , Estudo de Associação Genômica Ampla , Humanos , Inflamação/microbiologia , Cirrose Hepática/microbiologia , Metagenômica
18.
Gigascience ; 6(10): 1-12, 2017 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-29050374

RESUMO

The root microbes play pivotal roles in plant productivity, nutrient uptakes, and disease resistance. The root microbial community structure has been extensively investigated by 16S/18S/ITS amplicons and metagenomic sequencing in crops and model plants. However, the functional associations between root microbes and host plant growth are poorly understood. This work investigates the root bacterial community of foxtail millet (Setaria italica) and its potential effects on host plant productivity. We determined the bacterial composition of 2882 samples from foxtail millet rhizoplane, rhizosphere and corresponding bulk soils from 2 well-separated geographic locations by 16S rRNA gene amplicon sequencing. We identified 16 109 operational taxonomic units (OTUs), and defined 187 OTUs as shared rhizoplane core OTUs. The ß-diversity analysis revealed that microhabitat was the major factor shaping foxtail millet root bacterial community, followed by geographic locations. Large-scale association analysis identified the potential beneficial bacteria correlated with plant high productivity. Besides, the functional prediction revealed specific pathways enriched in foxtail millet rhizoplane bacterial community. We systematically described the root bacterial community structure of foxtail millet and found its core rhizoplane bacterial members. Our results demonstrated that host plants enrich specific bacteria and functions in the rhizoplane. The potentially beneficial bacteria may serve as a valuable knowledge foundation for bio-fertilizer development in agriculture.


Assuntos
Microbiota , Milhetes/microbiologia , Rizoma/microbiologia , Bactérias/classificação , Bactérias/genética , Código de Barras de DNA Taxonômico , Genoma Bacteriano , RNA Ribossômico 16S/genética
19.
Nat Med ; 23(7): 859-868, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28628112

RESUMO

Emerging evidence has linked the gut microbiome to human obesity. We performed a metagenome-wide association study and serum metabolomics profiling in a cohort of lean and obese, young, Chinese individuals. We identified obesity-associated gut microbial species linked to changes in circulating metabolites. The abundance of Bacteroides thetaiotaomicron, a glutamate-fermenting commensal, was markedly decreased in obese individuals and was inversely correlated with serum glutamate concentration. Consistently, gavage with B. thetaiotaomicron reduced plasma glutamate concentration and alleviated diet-induced body-weight gain and adiposity in mice. Furthermore, weight-loss intervention by bariatric surgery partially reversed obesity-associated microbial and metabolic alterations in obese individuals, including the decreased abundance of B. thetaiotaomicron and the elevated serum glutamate concentration. Our findings identify previously unknown links between intestinal microbiota alterations, circulating amino acids and obesity, suggesting that it may be possible to intervene in obesity by targeting the gut microbiota.


Assuntos
DNA Bacteriano/análise , Disbiose/microbiologia , Microbioma Gastrointestinal/genética , Metaboloma , Obesidade/microbiologia , Adiposidade , Adulto , Animais , Bacteroides/genética , Bacteroides thetaiotaomicron/genética , Cirurgia Bariátrica , Estudos de Casos e Controles , Disbiose/metabolismo , Feminino , Fusobacterium/genética , Gastrectomia , Ácido Glutâmico/sangue , Humanos , Masculino , Metagenoma , Camundongos , Obesidade/metabolismo , Obesidade/cirurgia , Ganho de Peso , Adulto Jovem
20.
Gigascience ; 6(7): 1-11, 2017 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-28655159

RESUMO

The inflammatory intestinal disorder Crohn's disease (CD) has become a health challenge worldwide. The gut microbiota closely interacts with the host immune system, but its functional impact in CD is unclear. Except for studies on a small number of CD patients, analyses of the gut microbiota in CD have used 16S rDNA amplicon sequencing. Here we employed metagenomic shotgun sequencing to provide a detailed characterization of the compositional and functional features of the CD microbiota, comprising also unannotated bacteria, and investigated its modulation by exclusive enteral nutrition. Based on signature taxa, CD microbiotas clustered into 2 distinct metacommunities, indicating individual variability in CD microbiome structure. Metacommunity-specific functional shifts in CD showed enrichment in producers of the pro-inflammatory hexa-acylated lipopolysaccharide variant and a reduction in the potential to synthesize short-chain fatty acids. Disruption of ecological networks was evident in CD, coupled with reduction in growth rates of many bacterial species. Short-term exclusive enteral nutrition elicited limited impact on the overall composition of the CD microbiota, although functional changes occurred following treatment. The microbiotas in CD patients can be stratified into 2 distinct metacommunities, with the most severely perturbed metacommunity exhibiting functional potentials that deviate markedly from that of the healthy individuals, with possible implication in relation to CD pathogenesis.


Assuntos
Doença de Crohn/microbiologia , Microbioma Gastrointestinal , Adolescente , Adulto , Estudos de Casos e Controles , Doença de Crohn/dietoterapia , Nutrição Enteral/efeitos adversos , Nutrição Enteral/métodos , Ácidos Graxos/metabolismo , Feminino , Humanos , Lipopolissacarídeos/metabolismo , Masculino , Metagenoma , RNA Ribossômico 16S/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA