Department of Veterinary Medicine, University of Perugia, Perugia, Italy.
Department of Pharmaceutical Sciences, University of Perugia, Perugia, Italy.
PLoS One. 2018 Aug 23;13(8):e0202929. doi: 10.1371/journal.pone.0202929. eCollection 2018.
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder for which the current medical therapy is not completely effective. Bovine colostrum (BC) is a biological fluid rich in bioactive molecules that may have beneficial effects on several gastrointestinal disorders. The objectives of this study were to assess the preventive effects of BC supplementation in a mouse model of 2,4,6 trinitrobenzene sulfonic acid (TNBS)-induced colitis using a multidisciplinary approach. Specifically, the following parameters were evaluated: (i) disease activity index (DAI), (ii) histological score, (iii) expression levels of TLR4, anti- and pro-inflammatory cytokines, and (iv) count of some bacterial species of the intestinal microbiota. Mice received a daily suspension of BC (BC group, n = 12) or saline solution (control, CN group, n = 12) for 21 days before the intrarectal inoculation with 1% of TNBS solution. BC was well tolerated and did not induce any histological damage or clinical symptoms. After TNBS treatment, BC group showed a reduction of body weight (BW) loss (P<0.01) and histological score (P<0.05) compared to CN. Moreover, the expression levels of TLR4 (P<0.05), IL-1β (P<0.001), IL-8 (P<0.001), and IL-10 (P<0.001) were lower in mice administered with BC, while the concentrations of TNF-α did not show any differences between groups. Finally, the supplementation with BC resulted in a differential response to TNBS treatment in the bacterial count. In CN group, E. coli and Enterococci increased (P<0.001), while Anaerobes (P<0.01), Lactobacilli, and Bifidobacteria (P<0.001) reduced. Conversely, no significant changes in bacterial load were found after the inoculation of TNBS in BC pre-treated mice. This study confirms that TNBS-induced colitis model in mice is useful for studying the mechanisms involved in IBD pathogenesis and shows that pre-treatment with BC reduces the intestinal damages and clinical signs of the colitis. Molecular mechanisms and intestinal microflora could be involved in the protective effect of colostrum.
炎症性肠病（IBD）是一种慢性炎症性疾病，目前的医学治疗并不完全有效。牛初乳（BC）是一种富含生物活性分子的生物流体，可能对多种胃肠道疾病有有益的影响。本研究的目的是通过多学科方法评估 BC 补充剂对 2,4,6-三硝基苯磺酸（TNBS）诱导的结肠炎小鼠模型的预防作用。具体而言，评估了以下参数：（i）疾病活动指数（DAI），（ii）组织学评分，（iii）TLR4、抗炎和促炎细胞因子的表达水平，以及（iv）肠道微生物菌群中某些细菌种类的计数。小鼠在直肠内接种 1%TNBS 溶液前 21 天，每天接受 BC 混悬液（BC 组，n=12）或生理盐水溶液（对照，CN 组，n=12）。BC 耐受良好，未引起任何组织学损伤或临床症状。TNBS 治疗后，与 CN 相比，BC 组体重（BW）减轻（P<0.01）和组织学评分（P<0.05）降低。此外，BC 组小鼠 TLR4（P<0.05）、IL-1β（P<0.001）、IL-8（P<0.001）和 IL-10（P<0.001）的表达水平降低，而 TNF-α的浓度在两组之间没有差异。最后，BC 的补充对 TNBS 处理后的细菌计数产生了不同的反应。在 CN 组中，大肠杆菌和肠球菌增加（P<0.001），而厌氧菌（P<0.01）、乳酸杆菌和双歧杆菌减少（P<0.001）。相反，在 BC 预处理的小鼠接种 TNBS 后，细菌负荷没有明显变化。本研究证实，TNBS 诱导的结肠炎模型在小鼠中可用于研究 IBD 发病机制中涉及的机制，并表明 BC 预处理可减轻结肠炎的肠道损伤和临床症状。分子机制和肠道微生物群可能参与了牛初乳的保护作用。
