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

Abstract

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 How to cite this article: Suzuki R, Mishima M, Nagane M, et al. The novel sustained 3-hydroxybutyrate donor poly-D-3-hydroxybutyric acid prevents inflammatory bowel disease through upregulation of regulatory T-cells.

Prebiotic effect of poly‐D‐3‐hydroxybutyrate prevents dyslipidemia in obese mice

“…PHB is a biodegradable polyester that degrades in soil in the following order: oligomer, dimer, and monomer (3‐HB) 30 . In our previous study, we found that the concentration of 3‐HB in feces and blood was increased after PHB administration 22 . These suggest that gut microbiota, as well as soil bacteria, can degrade PHB to the monomer 3‐HB.…”

“…30 In our previous study, we found that the concentration of 3-HB in feces and blood was increased after PHB administration. 22 These suggest that gut microbiota, as well as soil bacteria, can degrade PHB to the monomer 3-HB. In this study, we investigated the prebiotic effects of PHB in C57BL/6N and ob/ob mice.…”

“…It is synthesized by various archaea and eubacteria, including Halomonas , Halobacterium , and Bacillus , and stored as multiple large granules in the bacterial cytoplasm 19–21 . We previously reported that PHB degraded by the gut microbiota to 3‐HB prevented the pathology of inflammatory bowel disease in a dextran sulfate sodium‐induced colitis model 22 . In addition, PHB improves the production of several SCFAs, such as acetate, propionate, and butyrate in micro‐mini pigs 23 .…”

“…[19][20][21] We previously reported that PHB degraded by the gut microbiota to 3-HB prevented the pathology of inflammatory bowel disease in a dextran sulfate sodium-induced colitis model. 22 In addition, PHB improves the production of several SCFAs, such as acetate, propionate, and butyrate in micro-mini pigs. 23 SCFAs and bacteria are associated with obesity and other related diseases.…”

The role of dietary prehabilitation on anastomotic healing

“…The profound influence of diet on the microbiome and the emerging central role of the microbiome on human health suggest that modulation of the microbiome prior to surgery may be a scientifically rational and practical approach to preventing postoperative complications [20]. Emerging evidence suggests that a high fiber, plant based low fat diet provides key substrates for the intestinal microbiota to produce metabolites such as tryptophan and short chain fatty acids (butyrate, propionate, acetate) each of which have profound effects on epithelial metabolism and the immune system at both the local level and systemically [21][22][23].…”