Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI, USA.
J Nutr. 2012 Jul;142(7):1336-42. doi: 10.3945/jn.111.154732. Epub 2012 Apr 11.
The gut microbiota plays an essential role in intestinal immunity. Prebiotics, including galacto-oligosaccharides (GOS), are fermentable fibers that beneficially affect the host by stimulating the growth of specific microbial populations. We investigated the effect of GOS on colitis development and on immune variables in Smad3-deficient mice treated with the pathogen Helicobacter hepaticus. Mice were supplemented daily with 5000 mg GOS/kg body weight 2 wk prior to infection and 4 wk postinfection, a time period during which colitis severity peaks in this model. Mice (n = 4-8/treatment at each time) were killed preinfection (0 d) and at 3, 7, and 28 d postinfection to evaluate immune variables in the spleen and in mesenteric lymph nodes (MsLN) by flow cytometry. Colon and cecum samples were collected for histopathologic analysis. Fecal pellets (n = 8-9/treatment) were collected prior to infection to measure relative changes in Bifidobacterium ssp. and Lactobacillum ssp. by real-time PCR. GOS significantly reduced colitis severity in response to H. hepaticus (P < 0.0001). This was associated with a significant increase in the percentage of NK cells in the spleen (P < 0.001) and in MsLN (P < 0.001) at 3 d postinfection and a 1.5-fold increase in fecal Bifidobacterium ssp. (P = 0.003). GOS stimulated NK expression of CCR9, a chemokine receptor involved in lymphocyte trafficking to the gut preinfection (0 d) in the blood (P = 0.02), spleen (P = 0.033), and MsLN (P = 0.017). In addition, GOS stimulated colonic IL-15 production 3 d postinfection (P < 0.001). These data suggest that GOS reduces colitis by modulating the function and trafficking of NK cells and may provide a novel therapeutic strategy for individuals with inflammatory bowel disease.
肠道微生物群在肠道免疫中起着至关重要的作用。益生元，包括半乳糖-低聚糖（GOS），是可发酵纤维，通过刺激特定微生物种群的生长，对宿主有益。我们研究了 GOS 对用病原体嗜胆菌感染的 Smad3 缺陷型小鼠结肠炎发展和免疫变量的影响。在感染前 2 周和感染后 4 周期间，每天给小鼠补充 5000mg GOS/kg 体重，在这个模型中，结肠炎的严重程度在这个时间段达到峰值。在感染前（0 天）和感染后 3、7 和 28 天处死小鼠（每组 4-8 只），通过流式细胞术评估脾和肠系膜淋巴结（MsLN）中的免疫变量。收集结肠和盲肠样本进行组织病理学分析。在感染前收集粪便样本（每组 8-9 只），通过实时 PCR 测量双歧杆菌和乳杆菌相对变化。GOS 显著降低了对嗜胆菌的结肠炎严重程度（P < 0.0001）。这与感染后 3 天脾（P < 0.001）和 MsLN（P < 0.001）中 NK 细胞百分比的显著增加有关，粪便中双歧杆菌增加 1.5 倍（P = 0.003）。GOS 刺激 NK 表达 CCR9，一种在感染前（0 天）参与淋巴细胞向肠道迁移的趋化因子受体，在血液（P = 0.02）、脾（P = 0.033）和 MsLN（P = 0.017）中。此外，GOS 刺激感染后 3 天结肠产生 IL-15（P < 0.001）。这些数据表明，GOS 通过调节 NK 细胞的功能和迁移来减轻结肠炎，并可能为炎症性肠病患者提供一种新的治疗策略。
