Intestinal microbe-dependent ω3 lipid metabolite αKetoA prevents inflammatory diseases in mice and cynomolgus macaques

Takahiro Nagatake, Shigenobu Kishino, Emiko Urano, Haruka Murakami, Nahoko Kitamura, Kana Konishi, Harumi Ohno, Prabha Tiwari, Sakiko Morimoto, Eri Node, Jun Adachi, Yuichi Abe, Junko Isoyama, Kento Sawane, Tetsuya Honda, Asuka Inoue, Akiharu Uwamizu, Takashi Matsuzaka, Yoichi Miyamoto, So ichiro HirataAzusa Saika, Yuki Shibata, Koji Hosomi, Ayu Matsunaga, Hitoshi Shimano, Makoto Arita, Junken Aoki, Masahiro Oka, Akira Matsutani, Takeshi Tomonaga, Kenji Kabashima, Motohiko Miyachi, Yasuhiro Yasutomi, Jun Ogawa, Jun Kunisawa*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)


Dietary ω3 fatty acids have important health benefits and exert their potent bioactivity through conversion to lipid mediators. Here, we demonstrate that microbiota play an essential role in the body’s use of dietary lipids for the control of inflammatory diseases. We found that amounts of 10-hydroxy-cis-12-cis-15-octadecadienoic acid (αHYA) and 10-oxo-cis-12-cis-15-octadecadienoic acid (αKetoA) increased in the feces and serum of specific-pathogen-free, but not germ-free, mice when they were maintained on a linseed oil diet, which is high in α-linolenic acid. Intake of αKetoA, but not αHYA, exerted anti-inflammatory properties through a peroxisome proliferator-activated receptor (PPAR)γ-dependent pathway and ameliorated hapten-induced contact hypersensitivity by inhibiting the development of inducible skin-associated lymphoid tissue through suppression of chemokine secretion from macrophages and inhibition of NF-κB activation in mice and cynomolgus macaques. Administering αKetoA also improved diabetic glucose intolerance by inhibiting adipose tissue inflammation and fibrosis through decreased macrophage infiltration in adipose tissues and altering macrophage M1/M2 polarization in mice fed a high-fat diet. These results collectively indicate that αKetoA is a novel postbiotic derived from α-linolenic acid, which controls macrophage-associated inflammatory diseases and may have potential for developing therapeutic drugs as well as probiotic food products.

Original languageEnglish
Pages (from-to)289-300
Number of pages12
JournalMucosal Immunology
Issue number2
Publication statusPublished - 2022 Feb
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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