Lipids from stool

In this study, we investigated how positively and negatively-charged lipid extract from feces of standard chow-fed mice (NL), by a simple extraction method, impact cell functioning. MTT assays for assessing cell metabolic activity indicated that NL differently affects tumor-derived cell lines, reducing the viability of Hela and HepG2 cells but it does not affect PC3 cells. Viabilities of 3T3-L1 fibroblasts and MSCs were not affected by NL. Additionally, NL displayed partial PPAR γ agonist action on reporter gene assays and on differentiation of 3T3-L1 fibroblasts to adipocytes. Transcriptome analyses showed that NL suppresses inflammatory response via toll-like receptor 4 (TLR4) signaling and affects PPAR target gene expression. Lipidomic analyses revealed significant differences of positively and negatively-charged lipid content of CD and NL, with NL containing less cancer correlated lipids and more apoptosis and necroptosis lipids than chow diet. These findings indicate that NL affect important aspects of cellular function and, therefore, may be considered as a promising therapeutic alternative to fecal transplant (FT).

本研究采用简易提取方法，探究了标准普通饲料喂养小鼠粪便来源的正负电荷脂质提取物（NL）对细胞功能的影响。用于评估细胞代谢活性的MTT实验结果显示，NL对不同肿瘤来源细胞系的影响存在差异：可降低海拉细胞（Hela）与肝癌细胞（HepG2）的存活率，但不会影响PC3细胞的存活率。3T3-L1成纤维细胞与间充质干细胞（MSCs）的存活率未受NL影响。此外，NL在报告基因实验及3T3-L1成纤维细胞向脂肪细胞的分化过程中，表现出部分过氧化物酶体增殖物激活受体γ（PPARγ）激动剂活性。转录组分析结果表明，NL可通过Toll样受体4（TLR4）信号通路抑制炎症反应，并影响PPAR靶基因的表达。脂质组学分析显示，标准普通饲料组（CD）与NL的正负电荷脂质含量存在显著差异：相较于标准普通饲料，NL中与癌症相关的脂质含量更低，而凋亡与坏死性凋亡相关脂质含量更高。上述研究结果表明，NL可影响细胞功能的多个重要方面，因此有望成为粪便移植（FT）的潜在治疗替代方案。