Dataset Information

Genetic diversity of Escherichia coli in gut microbiota of patients with Crohn's disease discovered using metagenomic and genomic analyses.

ABSTRACT: BACKGROUND:Crohn's disease is associated with gut dysbiosis. Independent studies have shown an increase in the abundance of certain bacterial species, particularly Escherichia coli with the adherent-invasive pathotype, in the gut. The role of these species in this disease needs to be elucidated. METHODS:We performed a metagenomic study investigating the gut microbiota of patients with Crohn's disease. A metagenomic reconstruction of the consensus genome content of the species was used to assess the genetic variability. RESULTS:The abnormal shifts in the microbial community structures in Crohn's disease were heterogeneous among the patients. The metagenomic data suggested the existence of multiple E. coli strains within individual patients. We discovered that the genetic diversity of the species was high and that only a few samples manifested similarity to the adherent-invasive varieties. The other species demonstrated genetic diversity comparable to that observed in the healthy subjects. Our results were supported by a comparison of the sequenced genomes of isolates from the same microbiota samples and a meta-analysis of published gut metagenomes. CONCLUSIONS:The genomic diversity of Crohn's disease-associated E. coli within and among the patients paves the way towards an understanding of the microbial mechanisms underlying the onset and progression of the Crohn's disease and the development of new strategies for the prevention and treatment of this disease.

SUBMITTER: Tyakht AV

PROVIDER: S-EPMC6307143 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Genetic diversity of Escherichia coli in gut microbiota of patients with Crohn's disease discovered using metagenomic and genomic analyses.

Tyakht Alexander V AV Manolov Alexander I AI Kanygina Alexandra V AV Ischenko Dmitry S DS Kovarsky Boris A BA Popenko Anna S AS Pavlenko Alexander V AV Elizarova Anna V AV Rakitina Daria V DV Baikova Julia P JP Ladygina Valentina G VG Kostryukova Elena S ES Karpova Irina Y IY Semashko Tatyana A TA Larin Andrei K AK Grigoryeva Tatyana V TV Sinyagina Mariya N MN Malanin Sergei Y SY Shcherbakov Petr L PL Kharitonova Anastasiya Y AY Khalif Igor L IL Shapina Marina V MV Maev Igor V IV Andreev Dmitriy N DN Belousova Elena A EA Buzunova Yulia M YM Alexeev Dmitry G DG Govorun Vadim M VM

BMC genomics 20181227 1

<h4>Background</h4>Crohn's disease is associated with gut dysbiosis. Independent studies have shown an increase in the abundance of certain bacterial species, particularly Escherichia coli with the adherent-invasive pathotype, in the gut. The role of these species in this disease needs to be elucidated.<h4>Methods</h4>We performed a metagenomic study investigating the gut microbiota of patients with Crohn's disease. A metagenomic reconstruction of the consensus genome content of the species was ...[more]

PMID: 30587114

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Project description:Escherichia coli is a leading contributor to infectious diarrhea and child mortality worldwide, but it remains unknown how alterations in the gut microbiome vary for distinct E. coli pathotype infections and whether these signatures can be used for diagnostic purposes. Further, the majority of enteric diarrheal infections are not diagnosed with respect to their etiological agent(s) due to technical challenges. To address these issues, we devised a novel approach that combined traditional, isolate-based and molecular-biology techniques with metagenomics analysis of stool samples and epidemiological data. Application of this pipeline to children enrolled in a case-control study of diarrhea in Ecuador showed that, in about half of the cases where an E. coli pathotype was detected by culture and PCR, E. coli was likely not the causative agent based on the metagenome-derived low relative abundance, the level of clonality, and/or the virulence gene content. Our results also showed that diffuse adherent E. coli (DAEC), a pathotype that is generally underrepresented in previous studies of diarrhea and thus, thought not to be highly virulent, caused several small-scale diarrheal outbreaks across a rural to urban gradient in Ecuador. DAEC infections were uniquely accompanied by coelution of large amounts of human DNA and conferred significant shifts in the gut microbiome composition relative to controls or infections caused by other E. coli pathotypes. Our study shows that diarrheal infections can be efficiently diagnosed for their etiological agent and categorized based on their effects on the gut microbiome using metagenomic tools, which opens new possibilities for diagnostics and treatment.IMPORTANCEE. coli infectious diarrhea is an important contributor to child mortality worldwide. However, diagnosing and thus treating E. coli infections remain challenging due to technical and other reasons associated with the limitations of the traditional culture-based techniques and the requirement to apply Koch's postulates. In this study, we integrated traditional microbiology techniques with metagenomics and epidemiological data in order to identify cases of diarrhea where E. coli was most likely the causative disease agent and evaluate specific signatures in the disease-state gut microbiome that distinguish between diffuse adherent, enterotoxigenic, and enteropathogenic E. coli pathotypes. Therefore, our methodology and results should be highly relevant for diagnosing and treating diarrheal infections and have important applications in public health.

Dataset Information

Genetic diversity of Escherichia coli in gut microbiota of patients with Crohn's disease discovered using metagenomic and genomic analyses.

Publications

Genetic diversity of Escherichia coli in gut microbiota of patients with Crohn's disease discovered using metagenomic and genomic analyses.

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