Wang Qun, Xu Kangjie, Cai Xu, Wang Chujing, Cao Yong, Xiao Jie
Guangdong Provincial Key Laboratory of Nutraceuticals and Functional Foods, College of Food Science, South China Agricultural University, Guangzhou 510642, China.
Medical Science Research Center, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.
J Agric Food Chem. 2023 Mar 22;71(11):4571-4585. doi: 10.1021/acs.jafc.2c08444. Epub 2023 Mar 7.
Maintaining a steady state of mucus barrier is an important potential target for polyphenol to exert its anticolitis activity. This study elucidates the pivotal role of polyphenol rosmaric acid (RA) in regulating the mucus barrier function and alleviating inflammation by identifying its gut microbiota-derived metabolites and evaluating its inhibitory effect on inflammasomes in colitis mice. Results demonstrated that RA treatment promoted the proliferation of goblet cells and restored the level of mucus secretion, especially Muc2. RA reshaped the microbiota of colitis mice, particularly the boost of core probiotics, such as p. , f. , g. , g. , and g. -014. Nontargeted metabonomics and targeted metabonomics confirmed a significant increase in the bile acids and their metabolites (7-sulfocholic acid, stercobilin, chenodeoxycholic acid 3-sulfate, chenodeoxycholic acid sulfate, and ursodeoxycholic acid 3-sulfate), indole metabolites (()-2,3-dihydro-3,5-dihydroxy-2--3-indoleacetic acid, frovatriptan, 3-formyl-6-hydroxyindole, and brassicanal A), and short-chain fatty acids (SCFAs) (acetic acid, butyric acid, isobutyric acid, isovaleric acid, and valeric acid) that contributed to the strengthened mucus barrier function. In addition, being absorbed mainly in the lower digestive tract, RA inhibited the overexpression of inflammasomes (especially NLRP6) that occurred in colitis mice to promote the mucus secretion of goblet cells. These data confirmed that RA, as a promising candidate to enhance gut health, restored colonic mucus secretion in colitis mice by mediating the production of gut microbiota-derived metabolites and the overexpression of inflammasomes. The presented study provides scientific evidence explaining the apparent paradox of low bioavailability and high bioactivity in polyphenols.
维持黏液屏障的稳态是多酚发挥抗结肠炎活性的一个重要潜在靶点。本研究通过鉴定多酚迷迭香酸（RA）的肠道微生物衍生代谢产物，并评估其对结肠炎小鼠炎性小体的抑制作用，阐明了多酚迷迭香酸在调节黏液屏障功能和减轻炎症方面的关键作用。结果表明，RA治疗促进了杯状细胞的增殖，并恢复了黏液分泌水平，尤其是Muc2。RA重塑了结肠炎小鼠的微生物群，特别是核心益生菌的增加，如p. 、f. 、g. 、g. 和g. -014。非靶向代谢组学和靶向代谢组学证实，胆汁酸及其代谢产物（7-磺基胆酸、粪胆素、鹅去氧胆酸3-硫酸盐、鹅去氧胆酸硫酸盐和熊去氧胆酸3-硫酸盐）、吲哚代谢产物（()-2,3-二氢-3,5-二羟基-2--3-吲哚乙酸、夫罗曲普坦、3-甲酰基-6-羟基吲哚和芸苔醛A）以及短链脂肪酸（SCFAs）（乙酸、丁酸、异丁酸、异戊酸和戊酸）显著增加，这些物质有助于增强黏液屏障功能。此外，RA主要在消化道下段被吸收，抑制了结肠炎小鼠中发生的炎性小体（尤其是NLRP6）的过度表达，从而促进杯状细胞的黏液分泌。这些数据证实，RA作为一种有望改善肠道健康的候选物质，通过介导肠道微生物衍生代谢产物的产生和炎性小体的过度表达，恢复了结肠炎小鼠的结肠黏液分泌。本研究提供了科学证据，解释了多酚生物利用度低但生物活性高这一明显矛盾现象。
