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戊酸盐对培养的Caco-2上皮细胞单层肠道屏障功能的影响。

Effects of valerate on intestinal barrier function in cultured Caco-2 epithelial cell monolayers.

作者信息

Gao Guanzhen, Zhou Jingru, Wang Huiqin, Ding Yanan, Zhou Jianwu, Chong Pik Han, Zhu Liying, Ke Lijing, Wang Xin, Rao Pingfan, Wang Qiang, Zhang Longxin

机构信息

Food Nutrition Science Centre, School of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, Zhejiang, China.

State Key Laboratory of Breeding Base for Zhejiang Sustainable Pest and Disease Control, Institute of Plant Protection and Microbiology, Zhejiang Academy of Agricultural Sciences, Hangzhou, Zhejiang, China.

出版信息

Mol Biol Rep. 2022 Mar;49(3):1817-1825. doi: 10.1007/s11033-021-06991-w. Epub 2021 Nov 27.

Abstract

BACKGROUND

Short-chain fatty acids (SCFAs) are a group of microbial metabolites of undigested dietary fiber, protein and unabsorbed amino acids in the colon, well-known for their gut health promoting benefits. A relatively high intestinal level of valerate was found in the healthy human subjects. However, the intestinal protection effects and the underlying mechanism of valerate are waiting to be verified and elucidated.

METHODS AND RESULTS

In the present study, valerate, a SCFAs mainly converted from proteins or amino acids, was demonstrated to promote intestinal barrier function at its physiological concentrations of 0-4 mM in the Caco-2 cell monolayer model of intestinal barrier using transepithelial electrical resistance (TEER) assay and paracellular permeability assay. Valerate achieved the maximum increase in the TEER at 2 mM and reduced the paracellular permeability. Its intestinal barrier function promoting activity is similar to that of butyrate, with a broader range of effective concentrations than the later. Through western blot analysis, this activity is linked to the valerate-induced AMPK activation and tight junctions (TJs) assembly, but not to the reinforced expression of TJs related proteins.

CONCLUSIONS

It provides direct experimental evidence supporting valerate's function in intestinal health, implying the once under-valued function of valerate and its amino acid precursors. The valerate's role in regulating intestine homeostasis and its possible synergetic effects with other SCFAs warranted to be further investigated.

摘要

背景

短链脂肪酸(SCFAs)是结肠中未消化膳食纤维、蛋白质和未吸收氨基酸的一组微生物代谢产物,以其促进肠道健康的益处而闻名。在健康人体受试者中发现肠道中戊酸水平相对较高。然而,戊酸的肠道保护作用及其潜在机制尚待验证和阐明。

方法与结果

在本研究中,戊酸是一种主要由蛋白质或氨基酸转化而来的短链脂肪酸,在肠道屏障的Caco-2细胞单层模型中,通过跨上皮电阻(TEER)测定和细胞旁通透性测定,证明其在0-4 mM的生理浓度下可促进肠道屏障功能。戊酸在2 mM时使TEER达到最大增加,并降低了细胞旁通透性。其促进肠道屏障功能的活性与丁酸相似,有效浓度范围比丁酸更广。通过蛋白质印迹分析,这种活性与戊酸诱导的AMPK激活和紧密连接(TJs)组装有关,而与TJs相关蛋白的表达增强无关。

结论

本研究提供了直接的实验证据支持戊酸在肠道健康中的作用,暗示了戊酸及其氨基酸前体曾被低估的功能。戊酸在调节肠道稳态中的作用及其与其他短链脂肪酸可能的协同作用值得进一步研究。

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