Schink M, Konturek P C, Tietz E, Dieterich W, Pinzer T C, Wirtz S, Neurath M F, Zopf Y
First Department of Medicine, Hector Center for Nutrition, Exercise and Sports, Friedrich-Alexander-Universitaet Erlangen-Nuernberg, Erlangen, Germany.
Second Department of Medicine, Thuringia-Clinic Saalfeld, Saalfeld/Saale, Germany.
J Physiol Pharmacol. 2018 Aug;69(4). doi: 10.26402/jpp.2018.4.09. Epub 2018 Dec 9.
Histamine intolerance represents a controversially discussed disorder. Besides an impaired degradation of orally supplied histamine due to diamine oxidase (DAO) deficiency, a deranged gut flora may also contribute to elevated histamine levels. Our aim was to determine the intestinal bacterial composition in patients with proven histamine intolerance in comparison to other food intolerances and healthy controls. A total of 64 participants were included in the study, encompassing 8 patients with histamine intolerance (HIT), 25 with food hypersensitivity (FH), 21 with food allergy and 10 healthy controls (HC). All participants underwent blood testing for total and food-specific immunoglobulin E, plasma histamine and DAO serum activity. Stool samples were used to analyze stool histamine and zonulin levels and bacterial composition by 16s rRNA sequencing. No significant differences in stool histamine levels were observed, but HIT patients showed elevated levels of stool zonulin. Microbiota analysis revealed increased levels of Proteobacteria (5.4%) and a significantly reduced alpha-diversity in the HIT group (P = 0.019). On family level, HC showed a significantly higher abundance of Bifidobacteriaceae compared to other study groups (P = 0.005), with lowest levels in the HIT group (P = 0.036). Also significantly reduced abundances of the genera Butyricimonas (P = 0.026) and Hespellia (P = 0.025) were observed in the HIT patients, whereas Roseburia were significantly elevated (P = 0.021). We concluded that the altered occurrence of Proteobacteria and Bifidobacteriaceae, reduced alpha-diversity as well as elevated stool zonulin levels suggest a dysbiosis and intestinal barrier dysfunction in histamine intolerant patients, which in turn may play an important role in driving disease pathogenesis.
组胺不耐受是一种存在争议的疾病。除了因二胺氧化酶（DAO）缺乏导致口服组胺降解受损外，肠道菌群紊乱也可能导致组胺水平升高。我们的目的是确定经证实的组胺不耐受患者与其他食物不耐受患者及健康对照者的肠道细菌组成。该研究共纳入64名参与者，包括8名组胺不耐受患者（HIT）、25名食物过敏患者（FH）、21名食物过敏患者和10名健康对照者（HC）。所有参与者均接受了总免疫球蛋白E和食物特异性免疫球蛋白E、血浆组胺及DAO血清活性的血液检测。粪便样本用于分析粪便组胺和闭合蛋白水平，并通过16s rRNA测序分析细菌组成。未观察到粪便组胺水平有显著差异，但HIT患者的粪便闭合蛋白水平升高。微生物群分析显示，HIT组的变形菌门水平升高（5.4%），α多样性显著降低（P = 0.019）。在科水平上，与其他研究组相比，HC组双歧杆菌科的丰度显著更高（P = 0.005），在HIT组中最低（P = 0.036）。在HIT患者中还观察到丁酸单胞菌属（P = 0.026）和赫斯佩利亚菌属（P = 0.025）的丰度显著降低，而罗斯氏菌属显著升高（P = 0.021）。我们得出结论，变形菌门和双歧杆菌科的出现改变、α多样性降低以及粪便闭合蛋白水平升高表明组胺不耐受患者存在肠道菌群失调和肠屏障功能障碍，这反过来可能在推动疾病发病机制中起重要作用。
