A compromised developmental trajectory of the infant gut microbiome and metabolome in atopic eczema

Abstract

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.

RETRACTED ARTICLE: Role of the gut microbiome in chronic diseases: a narrative review

“…The pathogenesis of eczema has been attributed to skin-barrier dysfunctions, immune dysregulation as well as environmental–host–microbial interactions [ 30 ]. Environmental factors and modern lifestyle trends have been shown to indirectly contribute to pathogenesis of the disease through modulation of the gut microbiome [ 31 ].…”

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“…Little is known about the role of Bacteroides in vaginally born infants except their ability to metabolize HMOs, suggesting therefore a role in modulating the gut anaerobiosis. Their implication in early life deserves further attention [ 20 , 26 , 70 ] though two recent birth cohort studies suggest the role of Bacteroides in allergy prevention [ 71 , 72 ].…”

Multiomics Integration in Skin Diseases with Alterations in Notch Signaling Pathway: PlatOMICs Phase 1 Deployment

“…These papers were not taken into account for further processing. Therefore, only 5 papers were further considered [ 18 , 19 , 20 , 21 , 22 ]. None of these articles includes DDD or AOS; thus, nowadays, the multiomics perspective has not been used for both diseases.…”

“…Their results suggest that in infants affected by AD and allergen sensitization, the metabolome and gut microbiome are abnormal within the first three months of age. These alterations have been hypothesized to entail a decrement in propionate and butyrate-producing microorganisms [ 21 ]. However, the impact of the genetic background of the enrolled subjects has not been evaluated, with no consequent possibility of integrating the findings with the host genetic profile.…”