Elevated Concentration of Lipid in Neonatal Microbiome Predicts Later Risk for Asthma, Allergy

Researchers said they have identified the mechanics that link a pro-inflammatory lipid in the infant microbiome at birth to the later development of allergies and asthma.

The study was published Monday in Nature Microbiology.

The researchers, with the University of California, San Francisco (UCSF), had previously published work showing that 1-month-old infants who subsequently developed childhood atopy and/or asthma exhibited a disturbed gut microbiome and increased concentrations of 12,13-diHOME, a lipid found at high concentrations in the infants’ feces. 12,13-diHOME reduced the number and activity of immune cells called regulatory T cells, or Tregs, that normally suppress allergic inflammation.

The infants were part of the racially and ethnically diverse Wayne County Health, Environment, Allergy and Asthma Longitudinal Study (WHEALS), which recruited 1258 pregnant women between the ages of 21 and 49 years between August 2003 and November 2007 living near Detroit, Michigan. Stool samples from children were collected during home visits at 1 month and additional interviews were conducted at 6, 12, 24, and 48 months after birth. The 24-month appointment occurred at a study clinic, in which the child underwent evaluation by a board-certified allergist.

Treatment of human dendritic cells with 12,13-diHOME altered expression of peroxisome proliferator-activated receptor γ (PPARγ)-regulated genes and reduced anti-inflammatory cytokine secretion and the number of Treg cells in vitro. Shotgun metagenomic sequencing of the infants’ stool samples indicated that bacterial epoxide hydrolase (EH) genes are more abundant in the gut microbiome of infants who develop atopic or asthma later in childhood.

Three of these bacterial EH genes (3EH) specifically produce 12,13-diHOME.

In this study, researchers injected bacterial strains expressing 3EH into the gut of mice, which reduced the Treg cell numbers in the animals’ lungs and altered Treg and other immune cell function at a molecular level.

They then studied the microbial genes found in the stool samples from 41 infants aged 1 month in the study. They found that the number of copies of 3EH or the concentration of the lipid itself in the babies’ stool samples predicted which infants went on to develop allergy by age 2 or asthma by age 4.

The researchers replicated this finding in the stool samples of an independent cohort of 50 1-month-olds based in San Francisco.

“While these findings need to be replicated in an even larger study group, the fact that these 2 cohorts collected in demographically different populations in very different cities showed the same results gives us confidence that the association between this bacterial lipid and childhood asthma and allergy risk may generalize to a broader population,” said MD/PhD candidate Sophia Levan, who led the study, in a statement.

Senior author Susan Lynch, PhD, a professor of medicine at UCSF, said the “finding paves the way for early-life gut microbiome interventions to prevent these diseases from developing.”

The researchers noted that 12,13-diHOME is just 1 component of the microbiome that plays a role in immune dysfunction and susceptibility to childhood allergy and asthma.

Reference

Levan SR, Stamnes KA, Lin L, et al. Elevated faecal 12,13-diHOME concentration in neonates at high risk for asthma is produced by gut bacteria and impedes immune tolerance [published online June 22, 2019]. Nat Microbiol. doi: 10.1038/s41564-019-0498-2.