Dataset Information

Gut Microbiota-Metabolome Changes in Children With Diarrhea by Diarrheagenic E. coli.

ABSTRACT: Background: Diarrheagenic Escherichia coli (DEC) strains are a main cause of diarrhea worldwide in children under 5 years old. DEC virulence is strongly regulated by environmental conditions and metabolites produced by the gut microbiota in the intestinal tract. In this study, we evaluated changes in gut microbiota-metabolome in children with or without diarrhea produced by DEC pathotypes. Goal: To determine gut microbiota composition and metabolome in stool samples obtained from healthy children and children with diarrhea positive for DEC pathotypes. Methods: We analyzed a total of 16 age-paired stool samples: 8 diarrheal samples positive for one DEC pathotype and 8 stool samples from healthy children. To identify the microbiota composition, we sequenced the V3-V4 region of the 16S rRNA and determined operational phylogenetic units (OPU). OPU were then used to predict metabolic pathways using the PICRUSt2 software. The presence of metabolites in stool samples was determined by LC-MS. A correlation analysis was performed with the main genera from each group and main metabolites. Bacteria associated with variance of main metabolites were identified using the MIMOSA2 software. Results: DEC and healthy groups showed a statistically different microbiota composition. A decrease in Firmicutes together with an increase in Bacteroidetes and Proteobacteria was found in the DEC group compared to the healthy group. Metabolic pathway predictions based on microbiota diversity showed that pathways involved in histidine and L-ornithine metabolism were significantly different between groups. A total of 88 metabolites detected by LC-MS were included in the metabolome analysis. We found higher levels of histamine and lower levels of ornithine in DEC samples than in the healthy group. Histamine and L-ornithine were associated with a specific microbiota species and the corresponding metabolic pathways. Conclusion: Stool samples from healthy children and children positive for DEC displayed a differential metabolome and microbiota composition. A strong correlation between a gut microbiota species and certain metabolites, such as histamine and L-ornithine, was found in the DEC group. This information might be useful to identify mechanisms and signaling molecules involved in the crosstalk between microbiota and DEC pathotypes.

SUBMITTER: Gallardo P

PROVIDER: S-EPMC7531578 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Gut Microbiota-Metabolome Changes in Children With Diarrhea by Diarrheagenic E. coli.

Gallardo Pablo P Izquierdo Mariana M Vidal Roberto M RM Soto Francisco F Ossa Juan C JC Farfan Mauricio J MJ

Frontiers in cellular and infection microbiology 20200918

Background: Diarrheagenic Escherichia coli (DEC) strains are a main cause of diarrhea worldwide in children under 5 years old. DEC virulence is strongly regulated by environmental conditions and metabolites produced by the gut microbiota in the intestinal tract. In this study, we evaluated changes in gut microbiota-metabolome in children with or without diarrhea produced by DEC pathotypes. Goal: To determine gut microbiota composition and metabolome in stool samples obtained ...[more]

PMID: 33072619

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Project description:Background: Diarrheagenic Escherichia coli (DEC) strains are a major cause of diarrhea in children under 5 years of age worldwide. DEC pathogenicity relies on the interaction of bacteria with environmental factors, including the host's resident gut microbiota. Previous reports have shown changes in the gut microbiota's composition during episodes of diarrhea, which may increase the pathogenicity of DEC strains. More intense and detailed identification of microbiota strains specifically associated with DEC infections and disease is needed to pinpoint their role in DEC pathogenicity. Aim: To identify resident indicative bacterial taxa in DEC-positive diarrhea stool samples of Chilean children. Methods: We analyzed 63 diarrheal stool samples from children 1-5 years of age by FilmArray® GI in order to identify a potential pathogen and to group diarrhea episodes into those caused by DEC as sole pathogen (DEC group, 32 samples) and those caused by an enteric virus as sole pathogen (viral group, 31 samples). In addition, 30 stool samples from healthy children, negative for enteric pathogens, were evaluated (healthy group). The 16S rRNA gene was amplified and sequenced using 454 pyrosequencing. Sequences were clustered into operational taxonomic units (OTUs) at 99% identity and their representatives were used to assign them to operational phylogenetic units (OPUs) using a phylogenetic inference approach. Results: Taxa assignment using the OPU approach resulted in a lower number of units but with higher accuracy compared to the OTU approach. Data analysis indicated an increase in sequences belonging to the phylum Proteobacteria in the DEC group compared to the viral and healthy groups. Samples displayed a statistically different community structure by sample grouping by redundancy analysis and ANOVA. Escherichia albertii (p = 0.001), Citrobacter werkmanii (p = 0.001), Yersinia enterocolitica, subsp. paleartica (p = 0.048), and Haemophilus sputorum (p = 0.028) were indicative species for the DEC group as compared to the viral and healthy groups. Conclusion: Gut microbiota in Chilean children with DEC-positive diarrhea differed from microbiota associated with enteric virus and healthy children. Indicative species found in this study may prove relevant in advancing our understanding of the relationship between resident gut microbiota and DEC leading to the occurrence of disease.

Project description:Diarrhea is the leading infectious cause of childhood morbidity and mortality. Among bacterial agents, diarrheagenic Escherichia coli (DEC) is the major causal agent of childhood diarrhea in developing countries, particularly in children under the age of 5 years. Here, we performed a hospital-based prospective study to explore the pathotype distribution, epidemiological characteristics and antibiotic resistance patterns of DEC from <?5-year-old diarrheal children.Between August 2015 and September 2016, 684 stool samples were collected from children (<?5 years old) with acute diarrhea. All samples were cultured and identified by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) and biochemical tests. PCR was used for subtyping, and enteropathogenic E. coli (EPEC) isolates were identified simultaneously with serology. Furthermore, antimicrobial sensitivity tests and sequencing of antibiotic resistance-related genes were conducted.DEC strains were identified in 7.9% of the 684 stool samples. Among them, the most commonly detected pathotype was EPEC (50.0% of DEC), of which 77.8% were classified as atypical EPEC (aEPEC). Age and seasonal distribution revealed that DEC tended to infect younger children and to occur in summer/autumn periods. Multidrug-resistant DEC isolates were 66.7%; resistance rates to ampicillin, co-trimoxazole, cefazolin, cefuroxime, cefotaxime, and ciprofloxacin were ??50%. Among 5 carbapenem-resistant DEC, 60.0% were positive for carbapenemase genes (2 blaNDM-1 and 1 blaKPC-2). Among 30 cephalosporin-resistant DEC, 93.3% were positive for extended-spectrum ?-lactamase (ESBL) genes, with blaTEM-1 and blaCTX-M-55 being the most common types. However, no gyrA or gyrB genes were detected in 16 quinolone-resistant isolates. Notably, aEPEC, which has not received much attention before, also exhibited high rates of drug resistance (81.0%, 66.7%, and 14.3% for ampicillin, co-trimoxazole , and carbapenem resistance, respectively).EPEC was the most frequent DEC pathotype in acute diarrheal children, with aEPEC emerging as a dominant diarrheal agent in central China. Most DEC strains were multidrug-resistant, making even ciprofloxacin unsuitable for empiric treatment against DEC infection. Among carbapenem-resistant DEC strains, those harboring blaNDM-1 and blaKPC-2 were the main causal agents. blaTEM-1 and blaCTX-M-55 were the major genetic determinants associated with high levels of cephalosporin resistance.

Project description:BackgroundIntrahepatic cholestasis in pregnancy (ICP) is the most common liver disease during pregnancy, and its exact etiology and course of progression are still poorly understood.AimTo investigate the link between the gut microbiota and serum metabolome in ICP patients.MethodsIn this study, a total of 30 patients were recruited, including 15 patients with ICP (disease group) and 15 healthy pregnant patients (healthy group). The serum nontarget metabolomes from both groups were determined. Amplification of the 16S rRNA V3-V4 region was performed using fecal samples from the disease and healthy groups. By comparing the differences in the microbiota and metabolite compositions between the two groups, the relationship between the gut microbiota and serum metabolites was also investigated.ResultsThe Kyoto Encyclopedia of Genes and Genomes analysis results showed that the primary bile acid biosynthesis, bile secretion and taurine and hypotaurine metabolism pathways were enriched in the ICP patients compared with the healthy controls. In addition, some pathways related to protein metabolism were also enriched in the ICP patients. The principal coordination analysis results showed that there was a distinct difference in the gut microbiota composition (beta diversity) between the ICP patients and healthy controls. At the phylum level, we observed that the relative abundance of Firmicutes was higher in the healthy group, while Bacteroidetes were enriched in the disease group. At the genus level, most of the bacteria depleted in ICP are able to produce short-chain fatty acids (e.g., Faecalibacterium, Blautia and Eubacterium hallii), while the bacteria enriched in ICP are associated with bile acid metabolism (e.g., Parabacteroides and Bilophila). Our results also showed that specific genera were associated with the serum metabolome.ConclusionOur study showed that the serum metabolome was altered in ICP patients compared to healthy controls, with significant differences in the bile, taurine and hypotaurine metabolite pathways. Alterations in the metabolization of these pathways may lead to disturbances in the gut microbiota, which may further affect the course of progression of ICP.

Dataset Information

Gut Microbiota-Metabolome Changes in Children With Diarrhea by Diarrheagenic E. coli.

Publications

Gut Microbiota-Metabolome Changes in Children With Diarrhea by Diarrheagenic <i>E. coli</i>.

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