Wang Hanru, Jatmiko Yoga D, Bastian Susan E P, Mashtoub Suzanne, Howarth Gordon S
a School of Animal and Veterinary Sciences , University of Adelaide , Adelaide , South Australia , Australia.
b School of Agriculture , Food and Wine, University of Adelaide , Adelaide , South Australia , Australia.
Nutr Cancer. 2017 Feb-Mar;69(2):307-318. doi: 10.1080/01635581.2017.1263747. Epub 2017 Jan 17.
Faecalibacterium prausnitzii (Fp) and Escherichia coli Nissle 1917 (EcN) are probiotics, which have been reported to ameliorate certain gastrointestinal disorders. We evaluated the effects of supernatants (SN) derived from Fp and EcN on 5-fluorouracil (5-FU)-treated intestinal cells and in a rat model of mucositis. In vitro: IEC-6, Caco-2, and T-84 cells were analyzed for viability and monolayer permeability. In vivo: Female dark agouti rats were gavaged with Fp or EcN SN and injected intraperitoneally with saline (control) or 5-FU to induce mucositis. Rats were euthanized and intestinal tissues collected for myeloperoxidase assay and histological analyses. In vitro: Caco-2 cell viability was further reduced when treated with Fp SN + 5-FU compared to 5-FU controls. In both Caco-2 and T-84 cells, Fp SN partially prevented the decrease in transepithelial electrical resistance (TER) caused by 5-FU administration. In vivo: 5-FU-injected rats administered Fp SN or EcN SN partly prevented body weight loss and normalized water intake compared to 5-FU controls. These results suggest a growth inhibitory mechanism of Fp SN action on transformed epithelial cells that could be mediated by effects on tight junctions. Factors derived from Fp SN and EcN SN could have a role in reducing the severity of intestinal mucositis.
普拉梭菌(Fp)和大肠杆菌Nissle 1917(EcN)是益生菌,据报道可改善某些胃肠道疾病。我们评估了Fp和EcN的上清液(SN)对5-氟尿嘧啶(5-FU)处理的肠细胞以及在黏膜炎大鼠模型中的作用。体外实验:分析IEC-6、Caco-2和T-84细胞的活力和单层通透性。体内实验:给雌性深色刺鼠灌胃Fp或EcN的SN,并腹腔注射生理盐水(对照)或5-FU以诱导黏膜炎。对大鼠实施安乐死并收集肠道组织用于髓过氧化物酶测定和组织学分析。体外实验:与5-FU对照组相比,用Fp SN + 5-FU处理时Caco-2细胞活力进一步降低。在Caco-2和T-84细胞中,Fp SN均部分阻止了5-FU给药引起的跨上皮电阻(TER)降低。体内实验:与5-FU对照组相比,注射5-FU并给予Fp SN或EcN SN的大鼠部分预防了体重减轻并使水摄入量恢复正常。这些结果表明Fp SN对转化上皮细胞的生长抑制机制可能由对紧密连接的影响介导。Fp SN和EcN SN衍生的因子可能在减轻肠道黏膜炎的严重程度方面发挥作用。