Butyrate is only one of several growth inhibitors produced during gut flora-mediated fermentation of dietary fibre sources
Butyrate is only one of several growth inhibitors produced during gut flora-mediated fermentation of dietary fibre sources
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DOI：
10.1079/bjn20031003
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发表时间：
2003-12-01
影响因子：
3.6
通讯作者：
Pool-Zobel, BL
中科院分区：
文献类型：
--
作者：
Beyer-Sehlmeyer, G;Glei, M;Pool-Zobel, BL
膳食纤维来源经肠道菌群发酵产生短链脂肪酸 (SCFA) 以及降解的植物化学物质和植物营养素。丁酸盐是一种主要的 SCFA，通过抑制肿瘤细胞的生长并增强其分化而具有潜在的化学保护作用。相反，它可以通过诱导谷胱甘肽 S-转移酶 (GST) 和增强化疗耐药性，为转化细胞带来正选择压力。事实上，人们对丁酸的活性如何受到其他发酵产物的影响一无所知。为了研究这种相互作用，将多种膳食纤维来源与人类粪便浆体外发酵，分析 SCFA，并制备相应的 SCFA 混合物。用单独的 SCFA 或复合样品处理 HT29 结肠肿瘤细胞 72 小时。测定了细胞的生长、GST 活性和对 4-羟基壬烯醛的化学抗性。发酵产物比相应的 SCFA 混合物更能抑制细胞生长，并且 SCFA 混合物比丁酸盐更具活性，这可能分别是由于植物保护剂和丙酸盐也抑制细胞生长。只有丁酸盐诱导 GST，而化学抗性是由选定的 SCFA 混合物引起的，但不是由所有相应的发酵样品引起的。总之，发酵上清液组分含有以下化合物：（1）增强丁酸盐（丙酸盐，植物化学组分）的抗增殖特性； (2) 不改变其诱导消费税的能力； (3)防止肿瘤细胞产生化疗耐药性。可以得出结论，发酵膳食纤维来源比单独的丁酸盐更有效地抑制肿瘤细胞生长，并且还含有抵消较高浓度的丁酸盐在肿瘤细胞中诱导的不期望的正选择压力的成分。
Dietary fibre sources are fermented by the gut flora to yield short-chain fatty acids (SCFA) together with degraded phytochemicals and plant nutrients. Butyrate, a major SCFA, is potentially chemoprotective by suppressing the growth of tumour cells and enhancing their differentiation. Conversely, it could lead to a positive selection pressure for transformed cells by inducing glutathione S-transferases (GST) and enhancing chemoresistance. Virtually nothing is known about how butyrate's activities are affected by other fermentation products. To investigate such interactions, a variety of dietary fibre sources was fermented with human faecal slurries in vitro, analysed for SCFA, and corresponding SCFA mixtures were prepared. HT29 colon tumour cells were treated for 72 h with individual SCFA or complex samples. The growth of cells, GST activity, and chemoresistance towards 4-hydroxynonenal were determined. Fermentation products inhibited cell growth more than the corresponding SCFA mixtures, and the SCFA mixtures were more active than butyrate, probably due to phytoprotectants and to propionate, respectively, which also inhibit cell growth. Only butyrate induced GST, whereas chemoresistance was caused by selected SCFA mixtures, but not by all corresponding fermentation samples. In summary, fermentation supernatant fractions contain compounds that: (1) enhance the anti-proliferative properties of butyrate (propionate, phytochemical fraction); (2) do not alter its capacity to induce GST; (3) prevent chemoresistance in tumour cells. It can be concluded that fermented dietary fibre sources are more potent inhibitors of tumour cell growth than butyrate alone, and also contain ingredients which counteract the undesired positive selection pressures that higher concentrations of butyrate induce in tumour cells.