Gut microbial metabolomics to understand allergies in early life

Savova, M.V.

In this thesis the links between allergy and intestinal health, the gut microbiome (GM), and external factors were studied by exploring the metabolome in longitudinal clinical studies and in vitro models.
Chapter 2 overviews of current knowledge on the role of the GM in IgE-mediated cow’s milk allergy (CMA).
In Chapter 3, infants at risk of allergies were followed during their first year. The findings showed significant age-related metabolomic shifts, likely driven by simultaneous alterations in host metabolism, feeding practices, and microbial composition, as well as C-section–associated alterations up to six months of age. Infants who developed allergies exhibited higher levels of long-chain fatty acids prior clinical onset.
Chapter 4 explored the link between IgE-mediated CMA, the GM, and bifidobacteria-promoting synbiotic supplementation. Only minor metabolomic changes were associated with tolerance to cow’s milk protein. Whereas, the synbiotics...Show moreIn this thesis the links between allergy and intestinal health, the gut microbiome (GM), and external factors were studied by exploring the metabolome in longitudinal clinical studies and in vitro models.
Chapter 2 overviews of current knowledge on the role of the GM in IgE-mediated cow’s milk allergy (CMA).
In Chapter 3, infants at risk of allergies were followed during their first year. The findings showed significant age-related metabolomic shifts, likely driven by simultaneous alterations in host metabolism, feeding practices, and microbial composition, as well as C-section–associated alterations up to six months of age. Infants who developed allergies exhibited higher levels of long-chain fatty acids prior clinical onset.
Chapter 4 explored the link between IgE-mediated CMA, the GM, and bifidobacteria-promoting synbiotic supplementation. Only minor metabolomic changes were associated with tolerance to cow’s milk protein. Whereas, the synbiotics significantly altered the fecal metabolome at 6 months, increasing aromatic lactic acids-metabolites of infant-type Bifidobacterium-indicating enhanced bifidobacterial activity.
Using an intestinal epithelium tubules-on-a-chip model, Chapter 5 demonstrated that exposure to pro-inflammatory cytokines results in impaired intestinal barrier under both serum-containing and serum-free conditions. Impaired gut barrier function was associated with elevated luminal prostaglandin levels, particularly under serum-free conditions.Show less

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Gut microbial metabolomics to understand allergies in early life