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Fecal IgA, Antigen Absorption, and Gut Microbiome Composition Are Associated With Food Antigen Sensitization in Genetically Susceptible Mice.

Publication ,  Journal Article
Smeekens, JM; Johnson-Weaver, BT; Hinton, AL; Azcarate-Peril, MA; Moran, TP; Immormino, RM; Kesselring, JR; Steinbach, EC; Orgel, KA; Staats, HF ...
Published in: Front Immunol
2020

Food allergy is a potentially fatal disease affecting 8% of children and has become increasingly common in the past two decades. Despite the prevalence and severe nature of the disease, the mechanisms underlying sensitization remain to be further elucidated. The Collaborative Cross is a genetically diverse panel of inbred mice that were specifically developed to study the influence of genetics on complex diseases. Using this panel of mouse strains, we previously demonstrated CC027/GeniUnc mice, but not C3H/HeJ mice, develop peanut allergy after oral exposure to peanut in the absence of a Th2-skewing adjuvant. Here, we investigated factors associated with sensitization in CC027/GeniUnc mice following oral exposure to peanut, walnut, milk, or egg. CC027/GeniUnc mice mounted antigen-specific IgE responses to peanut, walnut and egg, but not milk, while C3H/HeJ mice were not sensitized to any antigen. Naïve CC027/GeniUnc mice had markedly lower total fecal IgA compared to C3H/HeJ, which was accompanied by stark differences in gut microbiome composition. Sensitized CC027/GeniUnc mice had significantly fewer CD3+ T cells but higher numbers of CXCR5+ B cells and T follicular helper cells in the mesenteric lymph nodes compared to C3H/HeJ mice, which is consistent with their relative immunoglobulin production. After oral challenge to the corresponding food, peanut- and walnut-sensitized CC027/GeniUnc mice experienced anaphylaxis, whereas mice exposed to milk and egg did not. Ara h 2 was detected in serum collected post-challenge from peanut-sensitized mice, indicating increased absorption of this allergen, while Bos d 5 and Gal d 2 were not detected in mice exposed to milk and egg, respectively. Machine learning on the change in gut microbiome composition as a result of food protein exposure identified a unique signature in CC027/GeniUnc mice that experienced anaphylaxis, including the depletion of Akkermansia. Overall, these results demonstrate several factors associated with enteral sensitization in CC027/GeniUnc mice, including diminished total fecal IgA, increased allergen absorption and altered gut microbiome composition. Furthermore, peanuts and tree nuts may have inherent properties distinct from milk and eggs that contribute to allergy.

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Published In

Front Immunol

DOI

EISSN

1664-3224

Publication Date

2020

Volume

11

Start / End Page

599637

Location

Switzerland

Related Subject Headings

  • Peanut Hypersensitivity
  • Mice, Transgenic
  • Mice
  • Intestinal Absorption
  • Immunoglobulin A
  • Genetic Predisposition to Disease
  • Gastrointestinal Microbiome
  • Feces
  • Animals
  • Allergens
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Smeekens, J. M., Johnson-Weaver, B. T., Hinton, A. L., Azcarate-Peril, M. A., Moran, T. P., Immormino, R. M., … Kulis, M. D. (2020). Fecal IgA, Antigen Absorption, and Gut Microbiome Composition Are Associated With Food Antigen Sensitization in Genetically Susceptible Mice. Front Immunol, 11, 599637. https://doi.org/10.3389/fimmu.2020.599637
Smeekens, Johanna M., Brandi T. Johnson-Weaver, Andrew L. Hinton, M Andrea Azcarate-Peril, Timothy P. Moran, Robert M. Immormino, Janelle R. Kesselring, et al. “Fecal IgA, Antigen Absorption, and Gut Microbiome Composition Are Associated With Food Antigen Sensitization in Genetically Susceptible Mice.Front Immunol 11 (2020): 599637. https://doi.org/10.3389/fimmu.2020.599637.
Smeekens JM, Johnson-Weaver BT, Hinton AL, Azcarate-Peril MA, Moran TP, Immormino RM, et al. Fecal IgA, Antigen Absorption, and Gut Microbiome Composition Are Associated With Food Antigen Sensitization in Genetically Susceptible Mice. Front Immunol. 2020;11:599637.
Smeekens, Johanna M., et al. “Fecal IgA, Antigen Absorption, and Gut Microbiome Composition Are Associated With Food Antigen Sensitization in Genetically Susceptible Mice.Front Immunol, vol. 11, 2020, p. 599637. Pubmed, doi:10.3389/fimmu.2020.599637.
Smeekens JM, Johnson-Weaver BT, Hinton AL, Azcarate-Peril MA, Moran TP, Immormino RM, Kesselring JR, Steinbach EC, Orgel KA, Staats HF, Burks AW, Mucha PJ, Ferris MT, Kulis MD. Fecal IgA, Antigen Absorption, and Gut Microbiome Composition Are Associated With Food Antigen Sensitization in Genetically Susceptible Mice. Front Immunol. 2020;11:599637.

Published In

Front Immunol

DOI

EISSN

1664-3224

Publication Date

2020

Volume

11

Start / End Page

599637

Location

Switzerland

Related Subject Headings

  • Peanut Hypersensitivity
  • Mice, Transgenic
  • Mice
  • Intestinal Absorption
  • Immunoglobulin A
  • Genetic Predisposition to Disease
  • Gastrointestinal Microbiome
  • Feces
  • Animals
  • Allergens