Li Zihua, Zhang Shujie, Zhang Yudian, Chen Jin, Wu Fuqing, Liu Gang, Chen Guo-Qiang
School of Pharmaceutical Sciences, Tsinghua University, Beijing, 100084, China.
School of Life Sciences, Tsinghua University, Beijing, 100084, China.
Mol Nutr Food Res. 2021 Dec;65(24):e2100533. doi: 10.1002/mnfr.202100533. Epub 2021 Nov 15.
Inflammatory bowel disease and colorectal carcinogenesis (CRC) are common diseases without effective prevention approach. 3-Hydroxybutyrate (3HB) reported to have multiple functions as an oral food supplement. This study observes that 3HB prevents mouse colitis and CRC.
The sensitivity of wild type (WT) and GPR109a mice to colitis is compared using dextran sulfate sodium salt (DSS)-induced colitis model. Flow cytometry showed that 3HB cellular surface receptor GPR109a that can decrease the percentage of M1 macrophages from 50% of the DSS-induced acute colitis mouse group to 42% DSS+3HB group mediating the inhibitory effect on inflammation. Bone marrow transplantation experiments further demonstrated that the function of 3HB depended on bone marrow cells. Subsequently, the sensitivity of WT and GPR109a mice to CRC is compared using an azoxymethane-DSS-induced CRC mouse model. It is found that the activation of GPR109a inhibited CRC, depended on reduced myeloid-derived suppressor cells accumulation from 27% of the DSS group to 19% of the DSS+3HB group studied using flow cytometry.
It is concluded that 3HB significantly suppresses colonic inflammation and carcinogenesis, promising to benefit colon disease prevention in form of a food supplement.
炎症性肠病和结直肠癌(CRC)是常见疾病,目前尚无有效的预防方法。据报道,3-羟基丁酸(3HB)作为一种口服食品补充剂具有多种功能。本研究观察到3HB可预防小鼠结肠炎和结直肠癌。
使用葡聚糖硫酸钠(DSS)诱导的结肠炎模型比较野生型(WT)和GPR109a小鼠对结肠炎的敏感性。流式细胞术显示,3HB细胞表面受体GPR109a可将M1巨噬细胞的百分比从DSS诱导的急性结肠炎小鼠组的50%降至DSS+3HB组的42%,介导对炎症的抑制作用。骨髓移植实验进一步证明3HB的功能依赖于骨髓细胞。随后,使用氧化偶氮甲烷-DSS诱导的CRC小鼠模型比较WT和GPR109a小鼠对CRC的敏感性。结果发现,GPR109a的激活抑制了结直肠癌,这取决于通过流式细胞术研究发现髓源性抑制细胞的积累从DSS组的27%降至DSS+3HB组的19%。
得出结论,3HB可显著抑制结肠炎症和致癌作用,有望作为一种食品补充剂造福于结肠疾病的预防。