European Journal of Nutrition

, Volume 55, Issue 1, pp 139–146 | Cite as

Active Hexose Correlated Compound (AHCC) promotes an intestinal immune response in BALB/c mice and in primary intestinal epithelial cell culture involving toll-like receptors TLR-2 and TLR-4

  • Jean-François Mallet
  • Émilie Graham
  • Barry W. Ritz
  • Kohei Homma
  • Chantal MatarEmail author
Original Contribution



Active Hexose Correlated Compound (AHCC®) is a cultured mushroom extract that is commercially available and promoted for immune support. Available data suggest that AHCC supplementation affects immune cell populations and immune outcomes, including natural killer cell response to infection. The mechanism by which AHCC exerts its effects is not well understood. The present work aimed to characterize the immunomodulatory activity of AHCC in the gut and to study the effects of AHCC on toll-like receptor (TLR) signaling in intestinal epithelial cells (IECs).


BALB/c mice were fed AHCC by gavage. In vivo activities were assessed by immunohistochemistry and cytokine production. The effects of AHCC on ex vivo primary cell culture from IECs were examined after challenge with LPS or E. coli alone or in the presence of anti-TLR-2 and TLR-4 blocking antibodies.


Feeding AHCC resulted in increased IgA+ cells in the intestine and increased sIgA, IL-10, and IFN-γ in the intestinal fluid. In IECs, contact with AHCC increased IL-6 production but not to the pro-inflammatory level of positive controls, LPS and E. coli. Blocking TLR-2 and TLR-4 reduced the induction of IL-6 by AHCC, suggesting that these innate receptors are involved in generating the immune response of IECs to AHCC.


AHCC may play a role in the orchestration of immune response and the maintenance of immune homeostasis in part by priming the TLR-2 and TLR-4 gate at the intestinal epithelium. Such a response is likely due to the recognition of non-pathogenic food-associated molecular patterns (FAMPs) such as those found associated with other mushroom or yeast-derived compounds.


AHCC Toll-like receptor E. coli Infection Mushroom Innate FAMP 



We would like to thank Mr. Jairo Duarte for his help in the isolation of the intestinal epithelial cells. This work was made possible by a non-restrictive research grant from the manufacturer of AHCC, Amino Up Chemical Company, Sapporo, Japan.

Conflict of interest

Dr. Kohei Homma is employed at Amino Up Chemical Co., Ltd. as a research scientist. Amino Up Chemical is the developer and manufacturer of the AHCC product used in this study. The author has not received personal financial gain from sales of the AHCC product. All findings and views expressed in this paper are those of the authors and do not necessarily reflect the views of Amino Up Chemical. As the vice president of scientific and regulatory affairs for Atrium Innovations, Dr. Barry Ritz is involved in the commercialization of many natural products, including AHCC. Currently, two atrium companies, Douglas Laboratories and Pure Encapsulations, commercialize products that contain AHCC as an ingredient. The other authors have no conflict of interest to declare.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Jean-François Mallet
    • 1
  • Émilie Graham
    • 2
  • Barry W. Ritz
    • 3
  • Kohei Homma
    • 4
  • Chantal Matar
    • 2
    Email author
  1. 1.Cellular and Molecular Medicine, Faculty of MedicineUniversity of OttawaOttawaCanada
  2. 2.Nutrition Sciences Program, Faculty of Health SciencesUniversity of OttawaOttawaCanada
  3. 3.Nutrition Sciences Department, College of Nursing and Health ProfessionsDrexel UniversityPhiladelphiaUSA
  4. 4.Amino Up Chemical Company, Ltd.SapporoJapan

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