The novel sustained 3‐hydroxybutyrate donor poly‐D ‐3‐hydroxybutyric acid prevents inflammatory bowel disease through upregulation of regulatory T‐cells

• DOI: 10.1096/fj.202200919r
• Publication Date: 2022-12-23T13:00:59Z
• Authors: Rimina Suzuki; Mayuko Mishima; Masaki Nagane; Hinano Mizugaki; Takehito Suzuki; Mariko Komuro; Takuto Shimizu; Tomoki Fukuyama; Shiro Takeda; Masaya Ogata; Takayoshi Miyamoto; Naoyuki Aihara; Junichi Kamiie; Shinji Kamisuki; Hiroto Yokaryo; Tadashi Yamashita; Takumi Satoh
• Keywords: 0301 basic medicine; 03 medical and health sciences; 3-Hydroxybutyric Acid; Polyesters; Humans; Hydroxybutyrates; Inflammatory Bowel Diseases; T-Lymphocytes, Regulatory; Up-Regulation; 12. Responsible consumption; 3. Good health

Inflammatory bowel disease (IBD) is a chronic persistent intestinal disorder, with ulcerative colitis and Crohn's disease being the most common. However, the physio-pathological development of IBD is still unknown. Therefore, research on the etiology and treatment of IBD has been conducted using a variety of approaches. Short-chain fatty acids such as 3-hydroxybutyrate (3-HB) are known to have various physiological activities. In particular, the production of 3-HB by the intestinal microflora is associated with the suppression of various inflammatory diseases. In this study, we investigated whether poly-D-3-hydroxybutyric acid (PHB), a polyester of 3-HB, is degraded by intestinal microbiota and works as a slow-release agent of 3-HB. Further, we examined whether PHB suppresses the pathogenesis of IBD models. As long as a PHB diet increased 3-HB concentrations in the feces and blood, PHB suppressed weight loss and histological inflammation in a dextran sulfate sodium-induced IBD model. Furthermore, PHB increased the accumulation of regulatory T cells in the rectum without affecting T cells in the spleen. These results indicate that PHB has potential applications in treating diseases related to the intestinal microbiota as a sustained 3-HB donor. We show for the first time that biodegradable polyester exhibits intestinal bacteria-mediated bioactivity toward IBD. The use of bioplastics, which are essential materials for sustainable social development, represents a novel approach to diseases related to dysbiosis, including IBD.