Department of Pathology, University of North Dakota School of Medicine & Health Sciences, Grand Forks, ND, USA.
Department of Biomedical Sciences, University of North Dakota School of Medicine & Health Sciences, Grand Forks, ND, USA.
Brain Behav Immun. 2021 Jul;95:122-141. doi: 10.1016/j.bbi.2021.03.002. Epub 2021 Mar 9.
A number of studies have reported comorbidity of food allergies with various neuropsychiatric disorders, such as anxiety, depression, attention-deficit hyperactivity disorder, and autism. However, inconsistent results across clinical studies have left the association between food allergy and behavioral disorders inconclusive. We postulated that the heterogeneities in genetic background among allergic cohorts affect symptom presentation and severity of food allergy, introducing bias in patient selection criteria toward individuals with overt physical reactions. To understand the influence of genetic background on food allergy symptoms and behavioral changes beyond anaphylaxis, we generated mouse models with mild cow's milk allergy by sensitizing male and female C57BL/6J and BALB/cJ mice to a bovine whey protein, β-lactoglobulin (BLG; Bos d 5). We compared strain- and sex-dependent differences in their immediate physical reactions to BLG challenge as well as anxiety-like behavior one day after the challenge. While reactions to the allergen challenge were either absent or mild for all groups, a greater number of BLG-sensitized BALB/cJ mice presented visible symptoms and hypothermia compared to C57BL/6J mice. Interestingly, male mice of both strains displayed anxiety-like behavior on an elevated zero maze without exhibiting cognitive impairment with the cross maze test. Further characterization of plasma cytokines/chemokines and fecal microbiota also differentiated strain- and sex-dependent effects of BLG sensitization on immune-mediator levels and bacterial populations, respectively. These results demonstrated that the genetic variables in mouse models of milk allergy influenced immediate physical reactions to the allergen, manifestation of anxiety-like behavior, levels of immune responses, and population shift in gut microbiota. Thus, stratification of allergic cohorts by their symptom presentations and severity may strengthen the link between food allergy and behavioral disorders and identify a population(s) with specific genetic background that have increased susceptibility to allergy-associated behavioral disorders.
许多研究报告称，食物过敏与各种神经精神疾病有关，如焦虑、抑郁、注意缺陷多动障碍和自闭症。然而，临床研究结果不一致，使得食物过敏与行为障碍之间的关联仍不确定。我们推测，过敏队列中遗传背景的异质性会影响食物过敏的症状表现和严重程度，从而对具有明显身体反应的患者选择标准产生偏差。为了了解遗传背景对除过敏反应以外的食物过敏症状和行为变化的影响，我们通过使雄性和雌性 C57BL/6J 和 BALB/cJ 小鼠对牛乳清蛋白 β-乳球蛋白（BLG；Bos d 5）致敏，产生了轻度牛奶过敏的小鼠模型。我们比较了它们对 BLG 挑战的即时身体反应以及挑战后一天的焦虑样行为的品系和性别依赖性差异。虽然所有组的过敏原挑战反应要么不存在，要么很轻微，但与 C57BL/6J 小鼠相比，更多的 BLG 致敏 BALB/cJ 小鼠表现出明显的症状和体温过低。有趣的是，两种品系的雄性小鼠在高架零迷宫上表现出焦虑样行为，而在十字迷宫测试中没有表现出认知障碍。进一步表征血浆细胞因子/趋化因子和粪便微生物群也分别区分了 BLG 致敏对免疫介质水平和细菌种群的品系和性别依赖性影响。这些结果表明，牛奶过敏小鼠模型中的遗传变量影响了对过敏原的即时身体反应、焦虑样行为的表现、免疫反应水平和肠道微生物群的种群变化。因此，通过其症状表现和严重程度对过敏队列进行分层，可能会加强食物过敏与行为障碍之间的联系，并确定具有特定遗传背景的人群（多个）对与过敏相关的行为障碍的易感性增加。
