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化疗诱导中性粒细胞减少症小鼠中,一种特定的营养组合可减少细菌易位。

Bacterial translocation is reduced by a specific nutritional combination in mice with chemotherapy-induced neutropenia.

机构信息

Nutricia Advanced Medical Nutrition, Danone Research, Centre for Specialised Nutrition, Wageningen, The Netherlands 6704 PH.

出版信息

J Nutr. 2011 Jul;141(7):1292-8. doi: 10.3945/jn.110.136986. Epub 2011 May 11.

DOI:10.3945/jn.110.136986
PMID:21562235
Abstract

Immune function is compromised in many cancer patients, leading to an increased risk of (infectious) complications. Chemotherapy-induced neutropenia is a common cause of treatment-induced immune suppression. In the present study, the effect of a specific nutritional combination (SNC) on bacterial translocation was studied in a model of chemotherapy-induced neutropenia in C3H/HeN mice colonized with Pseudomonas aeruginosa PAO-1. Dietary intervention started after stable colonization with P. aeruginosa to compare the SNC containing high protein, l-leucine, fish oil, and specific oligosaccharides to an isoenergetic control diet. After 3 wk, the mice were treated with cyclophosphamide to induce neutropenia. This rendered the mice susceptible to Pseudomonas translocation, which was quantified 5 d later. Intervention with the SNC resulted in a reduced incidence and intensity of bacterial translocation to the liver (P < 0.05) and a similar trend in the lungs (P ≤ 0.057). In addition, the SNC reduced the fecal pH (P < 0.05) and decreased P. aeruginosa counts in fecal samples (P < 0.05). Moreover, plasma concentrations of proinflammatory cytokines were correlated with the reduced bacterial translocation to the liver (ρ > 0.78; P < 0.001). In conclusion, dietary intervention with the SNC significantly reduced the incidence and severity of P. aeruginosa translocation in a mouse model of chemotherapy-induced immune suppression. Several mechanisms might have played a role, including the modulation of the intestinal microbiota, an improved gut barrier function, immune function, and a reduced inflammatory state. These results suggest an opportunity to develop new applications in cancer patients, with the aim to reduce infectious and other complications.

摘要

免疫功能在许多癌症患者中受到损害,导致(感染)并发症的风险增加。化疗引起的中性粒细胞减少是治疗引起免疫抑制的常见原因。在本研究中,我们研究了一种特定营养组合(SNC)对化疗诱导中性粒细胞减少症 C3H/HeN 小鼠中假单胞菌定植后细菌易位的影响。在稳定定植假单胞菌后开始饮食干预,以将含有高蛋白、亮氨酸、鱼油和特定寡糖的 SNC 与等能量对照饮食进行比较。3 周后,用环磷酰胺处理小鼠以诱导中性粒细胞减少。这使小鼠易受假单胞菌易位的影响,5 天后对其进行量化。SNC 的干预导致细菌向肝脏易位的发生率和严重程度降低(P < 0.05),向肺部的趋势相似(P ≤ 0.057)。此外,SNC 降低了粪便 pH 值(P < 0.05),并减少了粪便样本中假单胞菌的数量(P < 0.05)。此外,血浆中促炎细胞因子的浓度与肝脏易位减少相关(ρ> 0.78;P < 0.001)。总之,饮食干预 SNC 可显著降低化疗诱导免疫抑制小鼠模型中假单胞菌易位的发生率和严重程度。几种机制可能发挥了作用,包括调节肠道微生物群、改善肠道屏障功能、免疫功能和减轻炎症状态。这些结果表明有机会为癌症患者开发新的应用,以降低感染和其他并发症的风险。

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