High dietary fat intake induces a microbiota signature that promotes food allergy

J Allergy Clin Immunol. 2019 Jul;144(1):157-170.e8. doi: 10.1016/j.jaci.2019.01.043. Epub 2019 Feb 13.


Background: Diet-induced obesity and food allergies increase in tandem, but a potential cause-and-effect relationship between these diseases of affluence remains to be tested.

Objective: We sought to test the role of high dietary fat intake, diet-induced obesity, and associated changes in gut microbial community structure on food allergy pathogenesis.

Methods: Mice were fed a high-fat diet (HFD) for 12 weeks before food allergen sensitization on an atopic dermatitis-like skin lesion, followed by intragastric allergen challenge to induce experimental food allergy. Germ-free animals were colonized with a signature HFD or lean microbiota for 8 weeks before induction of food allergy. Food-induced allergic responses were quantified by using a clinical allergy score, serum IgE levels, serum mouse mast cell protease 1 concentrations, and type 2 cytokine responses. Accumulation of intestinal mast cells was examined by using flow cytometry and chloroacetate esterase tissue staining. Changes in the gut microbial community structure were assessed by using high-throughput 16S ribosomal DNA gene sequencing.

Results: HFD-induced obesity potentiates food-induced allergic responses associated with dysregulated intestinal effector mast cell responses, increased intestinal permeability, and gut dysbiosis. An HFD-associated microbiome was transmissible to germ-free mice, with the gut microbial community structure of recipients segregating according to the microbiota input source. Independent of an obese state, an HFD-associated gut microbiome was sufficient to confer enhanced susceptibility to food allergy.

Conclusion: These findings identify HFD-induced microbial alterations as risk factors for experimental food allergy and uncouple a pathogenic role of an HFD-associated microbiome from obesity. Postdieting microbiome alterations caused by overindulgence of dietary fat might increase susceptibility to food allergy.

Keywords: Food allergy; IgE; basophils; diet-induced obesity; dysbiosis; germ-free; high-fat diet; mast cells; microbiota.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • DNA, Bacterial / analysis
  • Diet, High-Fat*
  • Dysbiosis / blood
  • Dysbiosis / microbiology
  • Female
  • Food Hypersensitivity / blood
  • Food Hypersensitivity / microbiology*
  • Gastrointestinal Microbiome*
  • Immunoglobulin E / blood
  • Male
  • Mice, Inbred C57BL
  • Obesity / blood
  • Obesity / microbiology


  • DNA, Bacterial
  • Immunoglobulin E