A Lipopolysaccharide-Enriched Cow's Milk Allergy Microbiome Promotes a TLR4-Dependent Proinflammatory Intestinal...

Area of Science:

• Microbiology
• Immunology
• Gastroenterology

Background:

• Infants with cow's milk allergy (CMA) exhibit depleted allergy-protective gut bacteria.
• The role of gut microbiota in promoting allergic responses requires further investigation.

Purpose of the Study:

• To analyze the proinflammatory potential of a CMA-associated microbiota with increased Gram-negative bacteria.
• To investigate the role of Toll-like receptor 4 (TLR4) signaling in mediating the effects of this microbiota.

Main Methods:

• Colonization of mice (wild-type and TLR4-mutant) with a CMA-associated microbiota.
• Analysis of gene expression in the ileal epithelium.
• Flow cytometry to assess immune cell populations (Th17, Treg).
• Measurement of fecal immunoglobulin A (IgA).
• Metagenomic sequencing of the microbiota.

Main Results:

• CMA microbiota induced TLR4-dependent expression of proinflammatory genes (e.g., Saa1) and Th17-, B cell-, and Th2-associated genes.
• Mice colonized with CMA microbiota showed expanded Th17 and regulatory T cell populations and elevated fecal IgA.
• TLR4 signaling in CD11c+ cells was crucial for these responses.
• CMA microbiota exhibited increased abundance of lipopolysaccharide (LPS) biosynthesis genes.

Conclusions:

• A microbiota with higher LPS gene abundance is associated with TLR4-dependent proinflammatory gene expression.
• This microbiota induces a mixed type 2/type 3 immune response in mice.
• These findings may characterize a subset of infants with CMA.