A Compromised Developmental Trajectory of the Infant Gut Microbiome and Metabolome in Atopic Eczema -(targeted SCFAs profiling)
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo Sapiens
TISSUE(S): Feces
DISEASE(S): Eczema
PROVIDER: ST001431 | MetabolomicsWorkbench |
REPOSITORIES: MetabolomicsWorkbench
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Project description:Evidence is accumulating that the establishment of the gut microbiome in early life influences the development of atopic eczema. In this longitudinal study, we used integrated multi-omics analyses to infer functional mechanisms by which the microbiome modulates atopic eczema risk. We measured the functionality of the gut microbiome and metabolome of 63 infants between ages 3 weeks and 12 months with well-defined eczema cases and controls in a sub-cohort from the Growing Up in Singapore Toward healthy Outcomes (GUSTO) mother-offspring cohort. At 3 weeks, the microbiome and metabolome of allergen-sensitized atopic eczema infants were characterized by an enrichment of Escherichia coli and Klebsiella pneumoniae, associated with increased stool D-glucose concentration and increased gene expression of associated virulence factors. A delayed colonization by beneficial Bacteroides fragilis and subsequent delayed accumulation of butyrate and propionate producers after 3 months was also observed. Here, we describe an aberrant developmental trajectory of the gut microbiome and stool metabolome in allergen sensitized atopic eczema infants. The infographic describes an impaired developmental trajectory of the gut microbiome and metabolome in allergen-sensitized atopic eczema (AE) infants and infer its contribution in modulating allergy risk in the Singaporean mother-offspring GUSTO cohort. The key microbial signature of AE is characterized by (1) an enrichment of Escherichia coli and Klebsiella pneumoniae which are associated with accumulation of pre-glycolysis intermediates (D-glucose) via the trehalose metabolic pathway, increased gene expression of associated virulence factors (invasin, adhesin, flagellin and lipopolysaccharides) by utilizing ATP from oxidative phosphorylation and delayed production of butyrate and propionate, (2) depletion of Bacteroides fragilis which resulted in lower expression of immunostimulatory bacterial cell envelope structure and folate (vitamin B9) biosynthesis pathway, and (3) accompanied depletion of bacterial groups with the ability to derive butyrate and propionate through direct or indirect pathways which collectively resulted in reduced glycolysis, butyrate and propionate biosynthesis.
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Project description:Coal workers' pneumoconiosis (CWP) is a severe occupational disease resulting from prolonged exposure to coal dust. However, its pathogenesis remains elusive, compounded by a lack of early detection markers and effective treatments. Although the impact of gut microbiota on lung diseases is acknowledged, its specific role in CWP is unclear. This study aims to explore changes in the gut microbiome and metabolome in CWP, while also assessing the correlation between gut microbes and alterations in lung function. Fecal specimens from 43 CWP patients and 48 dust-exposed workers (DEW) were examined using 16S rRNA gene sequencing for microbiota and liquid chromatography-mass spectrometry for metabolite profiling. We observed similar gut microbial α-diversity but significant differences in flora composition (β-diversity) between patients with CWP and the DEW group. After adjusting for age using multifactorial linear regression analysis (MaAsLin2), the distinct gut microbiome profile in CWP patients revealed an increased presence of pro-inflammatory microorganisms such as Klebsiella and Haemophilus. Furthermore, in CWP patients, alterations in gut microbiota-particularly reduced α-diversity and changes in microbial composition-were significantly correlated with impaired pulmonary function, a relationship not observed in DEW. This underscores the specific impact of gut microbiota on pulmonary health in individuals with CWP. Metabolomic analysis of fecal samples from CWP patients and DEW identified 218 differential metabolites between the two groups, with a predominant increase in metabolites in CWP patients, suggesting enhanced metabolic activity in CWP. Key altered metabolites included various lipids, amino acids, and organic compounds, with silibinin emerging as a potential biomarker. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis linked these metabolites to pathways relevant to the development of pulmonary fibrosis. Additionally, studies on the interaction between microbiota and metabolites showed positive correlations between certain bacteria and increased metabolites in CWP, further elucidating the complex interplay in this disease state. Our findings suggest a potential contributory role of gut microbiota in CWP pathogenesis through metabolic regulation, with implications for diagnostic biomarkers and understanding disease mechanisms, warranting further molecular investigation.ImportanceThe findings have significant implications for the early diagnosis and treatment of coal workers' pneumoconiosis, highlighting the potential of gut microbiota as diagnostic biomarkers. They pave the way for new research into gut microbiota-based therapeutic strategies, potentially focusing on modifying gut microbiota to mitigate disease progression.
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