Sestak Karol, Thwin Hazel, Dufour Jason, Liu David X, Alvarez Xavier, Laine David, Clarke Adam, Doyle Anthony, Aye Pyone P, Blanchard James, Moehs Charles P
Division of Microbiology, Tulane National Primate Research Center, Covington, LA 70433, USA.
PreCliniTria, LLC., Mandeville, LA 70471, USA.
Nutrients. 2016 Jun 28;8(7):401. doi: 10.3390/nu8070401.
Celiac disease (CD) is an autoimmune disorder that affects approximately three million people in the United States. Furthermore, non-celiac gluten sensitivity (NCGS) affects an estimated additional 6% of the population, e.g., 20 million in the U.S. The only effective treatment of CD and NCGS requires complete removal of gluten sources from the diet. While required adherence to a gluten-free diet (GFD) is extremely difficult to accomplish, efforts to develop additional supportive treatments are needed. To facilitate these efforts, we developed a gluten-sensitive (GS) rhesus macaque model to study the effects of novel therapies. Recently reported results from phase one of this project suggest that partial improvement-but not remission-of gluten-induced disease can be accomplished by 100-fold reduction of dietary gluten, i.e., 200 ppm-by replacement of conventional dietary sources of gluten with a mutant, reduced gluten (RG) barley (lys3a)-derived source. The main focus of this (phase two) study was to determine if the inflammatory effects of the residual gluten in lys3a mutant barley grain could be further reduced by oral supplementation with a prolylendopeptidase (PE). Results reveal that PE supplementation of RG barley diet induces more complete immunological, histopathological and clinical remission than RG barley diet alone. The combined effects of RG barley diet and PE supplementation resulted in a further decrease of inflammatory mediators IFN-γ and TNF secretion by peripheral lymphocytes, as well as decreased plasma anti-gliadin and anti-intestinal tissue transglutaminase (TG2) antibodies, diminished active caspase production in small intestinal mucosa, and eliminated clinical diarrhea-all comparable with a gluten-free diet induced remission. In summary, the beneficial results of a combined RG barley and PE administration in GS macaques may warrant the investigation of similar synergistic approaches.
乳糜泻（CD）是一种自身免疫性疾病，在美国约影响300万人。此外，非乳糜泻麸质敏感（NCGS）估计额外影响6%的人口，例如在美国有2000万人。CD和NCGS的唯一有效治疗方法是从饮食中完全去除麸质来源。虽然严格遵守无麸质饮食（GFD）极难做到，但仍需要努力开发其他辅助治疗方法。为推动这些努力，我们建立了一个麸质敏感（GS）恒河猴模型来研究新疗法的效果。该项目第一阶段最近报告的结果表明，通过用一种突变的、麸质含量降低（RG）的大麦（lys3a）来源替代传统饮食中的麸质来源，将饮食中的麸质含量降低100倍（即200 ppm），可以实现麸质诱导疾病的部分改善，但不能缓解。本（第二阶段）研究的主要重点是确定口服脯氨酰内肽酶（PE）是否可以进一步降低lys3a突变大麦籽粒中残留麸质的炎症作用。结果显示，在RG大麦饮食中补充PE比单独使用RG大麦饮食能诱导更完全的免疫、组织病理学和临床缓解。RG大麦饮食和补充PE的联合作用导致外周淋巴细胞分泌的炎症介质IFN-γ和TNF进一步减少，血浆抗麦醇溶蛋白和抗肠组织转谷氨酰胺酶（TG2）抗体减少，小肠黏膜中活性半胱天冬酶产生减少，并消除了临床腹泻——所有这些都与无麸质饮食诱导的缓解相当。总之，在GS猕猴中联合使用RG大麦和PE的有益结果可能值得研究类似的协同方法。
