Inositol hexaphosphate promotes intestinal adaptation in short bowel syndrome via an HDAC3-mediated epigenetic pathway

  • Weipeng Wang Division of Pediatric Gastroenterology and Nutrition, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Department of Pediatric Surgery, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
  • Ying Wang Division of Pediatric Gastroenterology and Nutrition, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
  • Ying Lu Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China
  • Xinbei Tian Division of Pediatric Gastroenterology and Nutrition, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
  • Shanshan Chen Division of Pediatric Gastroenterology and Nutrition, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
  • Bo Wu Division of Pediatric Gastroenterology and Nutrition, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
  • Jun Du Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China
  • Yongtao Xiao Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University
  • Wei Cai Division of Pediatric Gastroenterology and Nutrition, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
DOI: https://doi.org/10.29219/fnr.v67.8694
Keywords: Inositol hexaphosphate, short bowel syndrome, intestinal adaptation, HDAC3, cell proliferation

Abstract

Background: Short bowel syndrome (SBS) has high morbidity and mortality rates, and promoting intestinal adaptation of the residual intestine is a critical treatment. Dietary inositol hexaphosphate (IP6) plays an important role in maintaining intestinal homeostasis, but its effect on SBS remains unclear. This study aimed at investigating the effect of IP6 on SBS and clarified its underlying mechanism.

Methods: Forty male Sprague–Dawley rats (3-week-old) were randomly assigned into four groups (Sham, Sham + IP6, SBS, and SBS + IP6 groups). Rats were fed standard pelleted rat chow and underwent resection of 75% of the small intestine after 1 week of acclimation. They received 1 mL IP6 treatment (2 mg/g) or sterile water daily for 13 days by gavage. Intestinal length, levels of inositol 1,4,5-trisphosphate (IP3), histone deacetylase 3 (HDAC3) activity, and proliferation of intestinal epithelial cell-6 (IEC-6) were detected.

Results: IP6 treatment increased the length of the residual intestine in rats with SBS. Furthermore, IP6 treatment caused an increase in body weight, intestinal mucosal weight, and IEC proliferation, and a decrease in intestinal permeability. IP6 treatment led to higher levels of IP3 in feces and serum, and higher HDAC3 activity of the intestine. Interestingly, HDAC3 activity was positively correlated with the levels of IP3 in feces (r = 0.49, P = 0.01) and serum (r = 0.44, P = 0.03). Consistently, IP3 treatment promoted the proliferation of IEC-6 cells by increasing HDAC3 activity in vitro. IP3 regulated the Forkhead box O3 (FOXO3)/Cyclin D1 (CCND1) signaling pathway.

Conclusion: IP6 treatment promotes intestinal adaptation in rats with SBS. IP6 is metabolized to IP3 to increase HDAC3 activity to regulate the FOXO3/CCND1 signaling pathway and may represent a potential therapeutic approach for patients with SBS.

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Published
2023-02-02
How to Cite
Wang W., Wang Y., Lu Y., Tian X., Chen S., Wu B., Du J., Xiao Y., & Cai W. (2023). Inositol hexaphosphate promotes intestinal adaptation in short bowel syndrome via an HDAC3-mediated epigenetic pathway. Food & Nutrition Research, 67. https://doi.org/10.29219/fnr.v67.8694
Issue
Vol 67 (2023)
Section
Original Articles
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