A purified diet affects intestinal epithelial proliferation and barrier functions through gut microbial alterations

Hiroaki Shiratori, Kisara M. Hattori, Kazuaki Nakata, Takuma Okawa, Seiga Komiyama, Yusuke Kinashi, Yuma Kabumoto, Yuria Kaneko, Motoyoshi Nagai, Tomoko Shindo, Nobuko Moritoki, Yuki I. Kawamura, Taeko Dohi, Daisuke Takahashi, Shunsuke Kimura, Koji Hase

研究成果: Article査読

抄録

The gut microbiota plays a crucial role in maintaining epithelial barrier function. Although multiple studies have demonstrated the significance of dietary factors on the gut microbiota and mucosal barrier function, the impact of a purified diet, which has long been used in various animal experiments, on intestinal homeostasis remains to be elucidated. Here, we compared the impact of two different types of diets, a crude diet and an AIN-93G-formula purified diet, on epithelial integrity and the gut microbiota. Purified diet-fed mice exhibited shorter villi and crypt lengths and slower epithelial turnover, particularly in the ileum. In addition, antimicrobial products, including REG3γ, were substantially decreased in purified diet-fed mice. Purified diet feeding also suppressed α1,2-fucosylation on the epithelial surface. Furthermore, the purified diet induced metabolic rewiring to fatty acid oxidation and ketogenesis. 16S ribosomal RNA gene sequencing of the ileal contents and mucus layer revealed distinct gut microbiota compositions between the purified and crude diet-fed mice. Purified diet feeding reduced the abundance of segmented filamentous bacteria (SFB), which potently upregulate REG3γand fucosyltransferase 2 (Fut2) by stimulating group 3 innate lymphoid cells (ILC3s) to produce IL-22. These observations illustrate that the intake of a crude diet secures epithelial barrier function by facilitating SFB colonization, whereas a purified diet insufficiently establishes the epithelial barrier, at least partly owing to the loss of SFB. Our data suggest that the influence of purified diets on the epithelial barrier integrity should be considered in experiments using purified diets.

本文言語English
ページ(範囲)223-240
ページ数18
ジャーナルInternational immunology
36
5
DOI
出版ステータスPublished - 2024 5月 1

ASJC Scopus subject areas

  • 免疫アレルギー学
  • 免疫学

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