Ho Sze Wing, El-Nezami Hani, Corke Harold, Ho Chun Sing, Shah Nagendra P
Food and Nutritional Science, School of Biological Sciences, The University of Hong Kong, Pokfulam Road, Hong Kong.
Biotechnology and Food Engineering Program, Guangdong Technion-Israel Institute of Technology, Shantou, Guangdong, China; Faculty of Biotechnology and Food Engineering, Technion-Israel Institute of Technology, Haifa, Israel.
J Nutr Biochem. 2022 Jan;99:108858. doi: 10.1016/j.jnutbio.2021.108858. Epub 2021 Sep 26.
Inflammatory bowel disease (IBD) is a group of chronic inflammatory gastrointestinal diseases that causes worldwide suffering. L. helveticus is a probiotic that can enhance intestinal barrier function via alleviation of excessive inflammatory response. Citrulline, a functional amino acid, has been reported to stimulate muscle synthesis and to function with a prebiotic-like action with certain Lactobacillus strains. The aim of this study was to investigate the potential synergistic effect of combining L. helveticus and citrulline on protection against damage induced by dextran sulfate sodium (DSS) in a mouse model. 6-week-old male C57BL/6J mice were fed with DSS water and randomly divided for administering with different milk treatments: 1) plain milk (control or DSS control), 2) 1% (w/v) citrulline enriched milk (Cit_milk), 3) milk fermented with L. helveticus (LHFM) and 4) DSS+milk fermented with L. helveticus with 1% (w/v) citrulline (Cit_LHFM). The treatment effects on the survival and macroscopic and microscopic signs were examined. All treatments presented different degrees of protective effects on attenuating the damages induced by DSS. All treatments reduced the body weight loss, disease activity index (DAI), histological scores, pro-inflammatory cytokine expression (IL-6, TNF-α and IFN-γ) and production (IL-4) (all P <0.05) and the tight junction (TJ) protein (zonula occluden-1 (ZO-1) expression. LHFM and Cit_LHFM improved survival rate (both at P<0.05). Particularly, Cit_LHFM showed greater effects on protecting the damages induced by DSS, especially in ameliorating colonic permeability, TJ protein (ZO-1, occludin and claudin-1) expression and distribution as well as in reducing IL-4 and IL-17 expression (all P <0.05). Our findings suggested that the combination of and citrulline had significant synergistic effect on protecting against injury from DSS-induced colitis. Therefore, citrulline enriched L. helveticus fermented milk is suggested to be a potential therapy for treating IBD.
炎症性肠病（IBD）是一类慢性炎症性胃肠道疾病，在全球范围内给患者带来痛苦。瑞士乳杆菌是一种益生菌，可通过减轻过度的炎症反应来增强肠道屏障功能。瓜氨酸是一种功能性氨基酸，据报道它能刺激肌肉合成，并与某些乳酸杆菌菌株产生类似益生元的作用。本研究的目的是在小鼠模型中研究瑞士乳杆菌和瓜氨酸联合使用对葡聚糖硫酸钠（DSS）诱导的损伤的潜在协同保护作用。给6周龄雄性C57BL/6J小鼠喂食含DSS的水，并随机分为不同的牛奶处理组进行给药：1）纯牛奶（对照组或DSS对照组），2）1%（w/v）富含瓜氨酸的牛奶（瓜氨酸牛奶），3）经瑞士乳杆菌发酵的牛奶（LHFM），4）含1%（w/v）瓜氨酸的经瑞士乳杆菌发酵的牛奶（瓜氨酸-LHFM）。检测各处理对小鼠存活情况以及大体和微观体征的影响。所有处理在减轻DSS诱导的损伤方面均呈现出不同程度的保护作用。所有处理均减轻了体重减轻、疾病活动指数（DAI）、组织学评分、促炎细胞因子表达（IL-6、TNF-α和IFN-γ）及产生（IL-4）（均P<0.05）以及紧密连接（TJ）蛋白（闭合蛋白-1（ZO-1）表达。LHFM和瓜氨酸-LHFM提高了存活率（均P<0.05）。特别地，瓜氨酸-LHFM在保护免受DSS诱导的损伤方面表现出更大的作用，尤其是在改善结肠通透性、TJ蛋白（ZO-1、闭合蛋白和紧密连接蛋白-1）表达及分布以及降低IL-4和IL-17表达方面（均P<0.05）。我们的研究结果表明，瑞士乳杆菌和瓜氨酸联合使用在预防DSS诱导的结肠炎损伤方面具有显著的协同作用。因此，富含瓜氨酸的瑞士乳杆菌发酵乳被认为是治疗IBD的一种潜在疗法。
