Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, The Netherlands.
Nutricia Research, Global Center of Excellence Immunology, 3584 CT Utrecht, The Netherlands.
Nutrients. 2020 Sep 11;12(9):2782. doi: 10.3390/nu12092782.
Bacterial gastroenteritis forms a burden on a global scale, both socially and economically. The Gram-positive bacterium is an inducer of gastrointestinal bacterial infections, often triggered following disruption of the microbiota by broad-spectrum antibiotics to treat other conditions. The clinical manifestatiaons, e.g., diarrhea, are driven by its toxins secretion, toxin A (TcdA) and toxin B (TcdB). Current therapies are focused on discontinuing patient medication, including antibiotics. However, relapse rates upon therapy are high (20-25%). Here, eighteen dietary proteins were evaluated for their capacity to restore gut health upon -derived TcdA exposure. We used bioengineered intestinal tubules to assess proteins for their beneficial effects by examining the epithelial barrier, cell viability, brush-border enzyme activity, IL-6 secretion, IL-8 secretion and nitric oxide (NO) levels upon TcdA challenge. TcdA effectively disrupted the epithelial barrier, increased mitochondrial activity, but did not affect alkaline phosphatase activity, IL-6, IL-8 and NO levels. Intervention with dietary proteins did not show a protective effect on epithelial barrier integrity or mitochondrial activity. However, bovine plasma and potato protein increased alkaline phosphatase activity, egg-white protein increased IL-6 and IL-8 release and wheat, lesser mealworm and yeast protein increased NO levels after TcdA exposure. Hence, dietary proteins can influence parameters involved in intestinal physiology and immune activation suggesting that supplementation with specific dietary proteins may be of benefit during infections.
细菌性肠胃炎在全球范围内给社会和经济带来了负担。革兰氏阳性菌是一种引起胃肠道细菌感染的病原体，通常在广谱抗生素治疗其他疾病时破坏微生物群后引发感染。腹泻等临床症状是由其毒素分泌引起的，包括毒素 A（TcdA）和毒素 B（TcdB）。目前的治疗方法侧重于停止患者用药，包括抗生素。然而，治疗后的复发率很高（20-25%）。在这里，我们评估了 18 种膳食蛋白在暴露于 TcdA 衍生毒素后的恢复肠道健康的能力。我们使用生物工程化的肠管来评估蛋白质的有益效果，方法是在 TcdA 挑战后检查上皮屏障、细胞活力、刷状缘酶活性、IL-6 分泌、IL-8 分泌和一氧化氮（NO）水平。TcdA 有效地破坏了上皮屏障，增加了线粒体活性，但对碱性磷酸酶活性、IL-6、IL-8 和 NO 水平没有影响。膳食蛋白的干预并没有显示出对上皮屏障完整性或线粒体活性的保护作用。然而，牛血浆和土豆蛋白增加了碱性磷酸酶活性，蛋清蛋白增加了 IL-6 和 IL-8 的释放，小麦、少鳞皮蠹和酵母蛋白增加了 TcdA 暴露后的 NO 水平。因此，膳食蛋白可以影响肠道生理学和免疫激活涉及的参数，这表明在感染期间补充特定的膳食蛋白可能有益。
