Rizzello Carlo G, De Angelis Maria, Di Cagno Raffaella, Camarca Alessandra, Silano Marco, Losito Ilario, De Vincenzi Massimo, De Bari Maria D, Palmisano Francesco, Maurano Francesco, Gianfrani Carmen, Gobbetti Marco
Department of Plant Protection and Applied Microbiology, University of Bari, Bari, Italy.
Appl Environ Microbiol. 2007 Jul;73(14):4499-507. doi: 10.1128/AEM.00260-07. Epub 2007 May 18.
Presently, the only effective treatment for celiac disease is a life-long gluten-free diet. In this work, we used a new mixture of selected sourdough lactobacilli and fungal proteases to eliminate the toxicity of wheat flour during long-time fermentation. Immunological (R5 antibody-based sandwich and competitive enzyme-linked immunosorbent assay [ELISA] and R5 antibody-based Western blot), two-dimensional electrophoresis, and mass spectrometry (matrix-assisted laser desorption ionization-time of flight, strong-cation-exchange-liquid chromatography/capillary liquid chromatography-electrospray ionization-quadrupole-time of flight [SCX-LC/CapLC-ESI-Q-TOF], and high-pressure liquid chromatography-electrospray ionization-ion trap mass spectrometry) analyses were used to determine the gluten concentration. Assays based on the proliferation of peripheral blood mononuclear cells (PBMCs) and gamma interferon production by PBMCs and intestinal T-cell lines (iTCLs) from 12 celiac disease patients were used to determine the protein toxicity of the pepsin-trypsin digests from fermented wheat dough (sourdough). As determined by R5-based sandwich and competitive ELISAs, the residual concentration of gluten in sourdough was 12 ppm. Albumins, globulins, and gliadins were completely hydrolyzed, while ca. 20% of glutenins persisted. Low-molecular-weight epitopes were not detectable by SCX-LC/CapLC-ESI-Q-TOF mass spectrometry and R5-based Western blot analyses. The kinetics of the hydrolysis of the 33-mer by lactobacilli were highly efficient. All proteins extracted from sourdough activated PBMCs and induced gamma interferon production at levels comparable to the negative control. None of the iTCLs demonstrated immunoreactivity towards pepsin-trypsin digests. Bread making was standardized to show the suitability of the detoxified wheat flour. Food processing by selected sourdough lactobacilli and fungal proteases may be considered an efficient approach to eliminate gluten toxicity.
目前,乳糜泻唯一有效的治疗方法是终身无麸质饮食。在这项研究中,我们使用了一种新的由选定的酸面团乳酸菌和真菌蛋白酶组成的混合物,以在长时间发酵过程中消除小麦粉的毒性。采用免疫分析(基于R5抗体的夹心和竞争性酶联免疫吸附测定[ELISA]以及基于R5抗体的蛋白质印迹法)、二维电泳和质谱分析(基质辅助激光解吸电离飞行时间质谱、强阳离子交换液相色谱/毛细管液相色谱-电喷雾电离-四极杆飞行时间质谱[SCX-LC/CapLC-ESI-Q-TOF]以及高压液相色谱-电喷雾电离-离子阱质谱)来测定麸质浓度。基于12名乳糜泻患者外周血单核细胞(PBMC)的增殖以及PBMC和肠道T细胞系(iTCL)产生γ干扰素的检测方法,用于测定发酵小麦面团(酸面团)中胃蛋白酶-胰蛋白酶消化物的蛋白质毒性。通过基于R5的夹心ELISA和竞争性ELISA测定,酸面团中麸质的残留浓度为12 ppm。白蛋白、球蛋白和醇溶蛋白被完全水解,而约20%的谷蛋白仍然存在。通过SCX-LC/CapLC-ESI-Q-TOF质谱和基于R5的蛋白质印迹分析未检测到低分子量表位。乳酸菌对33聚体的水解动力学非常高效。从酸面团中提取的所有蛋白质均能激活PBMC并诱导γ干扰素产生,其水平与阴性对照相当。没有一个iTCL对胃蛋白酶-胰蛋白酶消化物表现出免疫反应性。面包制作过程进行了标准化,以证明脱毒小麦粉的适用性。选择酸面团乳酸菌和真菌蛋白酶进行食品加工可能被认为是一种消除麸质毒性的有效方法。