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NIH grant 1R01AI202104-01: Determining Diet by Microbiome Interactions that Mitigate Early Life Susceptibility to Infection and Childhood Asthma Risk
Institute: {'code': 'AI', 'abbreviation': 'NIAID', 'name': 'National Institute of Allergy and Infectious Diseases', 'admin_org_id': '12500003', 'admin_funding_url': ''}. PI: Susan Veronica Lynch. Award: $825786.
Start: 2026-07-24T00:00:00.
PROJECT SUMMARY/ABSTRCT
Asthma affects an estimated 260 million people worldwide, yet its developmental origins remain poorly
understood, limiting effective prevention strategies. Severe early-life viral respiratory infections are a major risk
factor for childhood asthma, but the determinants of infection susceptibility and severity in infancy are
unknown. We previously developed an infant symptom score (S-score) and showed that elevated S-scores
predict asthma development in later childhood. Our work in an independent prospective mother-infant dyad
birth cohort the Binational Early Asthma and Microbiome Study (BEAMS), revealed that infants of Mexican-
ancestry born in the United States have significantly higher S-scores compared with their counterparts in
Mexico. Within this population, S-scores relate with significant dietary differentials in pregnancy and with gut
microbiomes that are compositionally, functionally, and metabolically divergent in both infancy and the prenatal
period. Lipids are the largest class of fecal metabolites associated with BEAMS infant S-scores; elevated S-
scores are linked with increased fecal concentrations of pro-inflammatory linoleic- and palmitic-acid derived
metabolites and the asthma-predictive oxylipin 12,13-diHOME. Low S-scores associate with fecal enrichment
of distinct and anti-inflammatory linoleic and α-linolenic acid derived metabolites. Strikingly, these relationships
between S-scores and fecal lipid metabolites are evident both in infancy and prenatally. Our data suggest that
divergent dietary lipid utilization strategies by functionally distinct gut microbiomes in the earliest phases of
human development, shape infant immune response to infection and asthma risk. However, nothing is known
of how functionally distinct prenatal and infant gut microbiomes differentially metabolize dietary lipids to
produce bioactive lipids that shape antiviral immunity. We propose that dietary lipid-microbiome interactions in
pregnancy and early infancy produce lipid metabolites that program host immune responses to respiratory viral
infection, thereby modulating risk of childhood asthma. We will test this using multi-omic analysis of BEAMS
fecal microbiomes to identify latent dietary and microbiome features in both the prenatal period (N=277) and
early infancy (N=277) that predict infant S-scores. These efforts will be complemented by a high-throughput in
vitro anaerobic prenatal and infant fecal microbiome cultivation approach to identify lipid-metabolizing microbes
and products that reproducibly protect against viral infection across participants in the BEAMS cohort.
Humanized germ-free mouse models will be used to determine how functionally distinct infant gut microbiomes
(based on S-scores) differentially process dietary lipids in vivo and assess the impact on immune response to
respiratory viral infection. We will also determine whether gut microbiomes use outer-membrane vesicles to
promote lipid-mediated regulation of immune responses in the airways. Thus, the proposed study will uncover
fundamental mechanisms by which gut microbiome metabolism of dietary lipids shapes early life susceptibility
to infection, antiviral immunity and childhood asthma risk.document fetched 2026-08-02 08:24