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Early infancy microbial and metabolic alterations affect risk of childhood asthma

Marie-Claire Arrieta1, Leah T Stiemsma2, Pedro A Dimitriu3

  • 1Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada. Department of Microbiology & Immunology, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada.

Science Translational Medicine
|October 2, 2015
PubMed

Insights

Infants at risk of asthma show gut microbial changes within the first 100 days. Specific bacteria and metabolites are reduced, suggesting a causal role in preventing pediatric asthma.

Area of Science:

  • Pediatric allergy and immunology
  • Microbiome research
  • Developmental origins of health and disease

Background:

  • Asthma is a leading chronic pediatric disease globally.
  • Early-life gut microbial dysbiosis is linked to experimental asthma in mice.
  • The role of early-life gut microbiota in human asthma development remains unclear.

Purpose of the Study:

  • To investigate the association between early-life gut microbiota and asthma risk in infants.
  • To identify specific microbial taxa and metabolites involved in asthma development.
  • To establish a causal link between gut bacteria and asthma prevention.

Main Methods:

  • Analysis of gut microbiota composition in 319 infants from the Canadian Healthy Infant Longitudinal Development (CHILD) Study.
  • Quantification of bacterial genera (Lachnospira, Veillonella, Faecalibacterium, Rothia) and fecal metabolites (acetate).
  • Gnotobiotic mouse model to test the causal role of identified bacterial taxa in airway inflammation.

Main Results:

  • Infants at risk of asthma exhibited transient gut microbial dysbiosis within the first 100 days of life.
  • Reduced abundance of Lachnospira, Veillonella, Faecalibacterium, and Rothia was observed in high-risk infants.
  • Decreased fecal acetate and dysregulated enterohepatic metabolites were associated with dysbiosis.
  • Inoculation of germ-free mice with these four bacteria ameliorated airway inflammation in adult offspring.

Conclusions:

  • Early-life gut microbial dysbiosis is associated with asthma risk in humans.
  • Specific bacterial taxa (Lachnospira, Veillonella, Faecalibacterium, Rothia) play a causal role in preventing asthma.
  • Findings support the development of microbe-based diagnostics and probiotic therapies for pediatric asthma prevention.

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