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Gut Microbiota-Metabolome Changes in Children With Diarrhea by Diarrheagenic E. coli
Pablo Gallardo1, Mariana Izquierdo1, Roberto M Vidal2
1Departamento de Pediatría y Cirugía Infantil, Facultad de Medicina, Hospital Dr. Luis Calvo Mackenna, Universidad de Chile, Santiago, Chile.
Insights
Diarrheagenic Escherichia coli (DEC) diarrhea in children is linked to distinct gut microbiota and metabolome profiles. Specific bacterial species correlate with altered histamine and L-ornithine levels, offering insights into disease mechanisms.
Area of Science:
- Microbiology
- Metabolomics
- Pediatric Gastroenterology
Background:
- Diarrheagenic Escherichia coli (DEC) is a major cause of diarrhea in young children globally.
- DEC virulence is influenced by gut microbiota metabolites and environmental factors.
- Understanding the interplay between gut microbiota and DEC is crucial for pediatric health.
Purpose of the Study:
- To investigate differences in gut microbiota composition and metabolome in children with DEC-associated diarrhea versus healthy children.
- To identify specific microbial and metabolic signatures associated with DEC infections.
- To explore correlations between gut bacteria and key metabolites.
Main Methods:
- Analysis of 16S rRNA gene sequences for microbiota composition in stool samples.
- Prediction of metabolic pathways using PICRUSt2 based on microbial data.
- Metabolomic profiling of stool samples using Liquid Chromatography-Mass Spectrometry (LC-MS).
- Correlation analysis between bacterial genera and detected metabolites using MIMOSA2.
Main Results:
- Significant differences in gut microbiota composition were observed between DEC-positive and healthy children.
- The DEC group showed a decrease in Firmicutes and an increase in Bacteroidetes and Proteobacteria.
- Metabolic pathways related to histidine and L-ornithine metabolism differed significantly.
- Elevated histamine and reduced ornithine levels were found in DEC samples, correlated with specific bacterial species and pathways.
Conclusions:
- Children with DEC diarrhea exhibit distinct gut microbiota and metabolome profiles compared to healthy children.
- A strong association exists between specific gut bacteria and metabolites like histamine and L-ornithine in DEC infections.
- These findings may elucidate signaling molecules and mechanisms in the host-pathogen-microbiota interaction.
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.
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