Ozone Responses and Diet: Does Sex Determine the Relationship?
Ozone Responses and Diet: Does Sex Determine the Relationship?
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臭氧反应和饮食：性别决定这种关系吗？
DOI：
10.1165/rcmb.2020-0042ed
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发表时间：
2020
影响因子：
6.4
通讯作者：
Vose,Aaron
中科院分区：
文献类型：
--
作者：
Tighe,RobertM;Vose,Aaron
环境空气污染显然与不良健康影响有关（1），是全球疾病负担的十大贡献者（2）。尽管努力管制这些接触，但对健康的不利影响仍然存在。因此，在减缓努力的同时，我们需要重点了解导致个人对空气污染敏感性的因素。从概念上讲，这些被定义为基因与环境的相互作用（3）。在这一框架内，个人的遗传组成影响他或她对环境中暴露的反应。然而，我们越来越意识到，非遗传宿主因素，如年龄，肥胖，糖尿病和饮食，影响空气污染的反应。这些因素之间的相互作用才刚刚开始解开。例如，最近的文献已经确定，臭氧（O3）肺反应具有性别特异性影响。几个实验室的工作表明，雄性和雌性小鼠表现出不同的O3诱导的气道高反应性（AHR）（4），这些影响与性激素（5，6）或对微生物组的性别依赖性影响（7）有关。虽然修改性激素是一个有趣的实验目标，作为一个目标战略，以减少O3的健康影响，它可能有有限的吸引力。或者，微生物组可以通过饮食来改变，因此饮食改变可能是一种可行的策略。在本期杂志中，Tashiro及其同事（pp. 503-512）探索饮食调整对急性O3暴露的肺反应的影响（8）。使用富含不同类型膳食纤维（果胶和纤维素）或无纤维饮食的小鼠，他们进行了一些有趣的观察，这些观察与性别有关。在雄性小鼠中，富含果胶的饮食引起O3诱导的AHR在最高乙酰甲胆碱剂量的轻度增加，而富含纤维素的饮食引起AHR的显着减少。相反，雌性小鼠表现出增强O3诱导的AHR反应的果胶和纤维素丰富的饮食。无纤维饮食不影响O3诱导的雄性小鼠AHR。与预期的相反，雌性小鼠对果胶和纤维素饮食的反应增强，喂食无纤维饮食的雌性小鼠也表现出增强的AHR，类似于它们对富含纤维饮食的反应。这些AHR效应似乎在很大程度上与O3诱导的损伤或炎症效应无关，这表明在该模型中，损伤并没有驱动AHR反应。为了探索饮食和性别依赖性AHR反应的潜在机制，作者测量了性激素，并给小鼠喂食无纤维饮食丙酸盐以减少短链脂肪酸。丙酸盐给药并没有改变喂无纤维饮食的雌性动物的AHR，性激素与性别依赖性饮食表型无关。基于这些发现，作者评估了性别依赖性，饮食诱导的微生物组变化，以解释观察到的表型。与果胶饮食相比，在喂食纤维素饮食的雄性小鼠中发现了更大的生物多样性和丰富性，并且在喂食任何一种饮食的雌性小鼠中注意到了总体上较小的影响。然而，在雌性小鼠中使用无纤维饮食对微生物群落结构的影响要大得多。一项统计分析，以确定潜在的协会显示，四个分类群（肠球菌科，乳酸杆菌，布劳特氏菌，链球菌科）与观察到的饮食反应的性别差异O3诱导AHR。Tashiro及其同事提出的数据建立在一系列研究的基础上，这些研究主要由该实验室小组开发，探索了微生物组在O3诱导的肺反应中的作用。
Ambient air pollution clearly associates with adverse health effects (1) and is a top 10 contributor to the global disease burden (2). Despite efforts to regulate these exposures, adverse health effects remain. Therefore, in parallel with mitigation efforts, we need to focus on understanding the factors that drive an individual’s susceptibility to air pollution. Conceptually, these are defined as gene-by-environment interactions (3). In this framework, an individual’s genetic composition influences his or her response to exposures in the environment. However, we are increasingly aware that nongenetic host factors, such as age, obesity, diabetes mellitus, and diet, influence air pollution responses. The interactions between these factors are just beginning to be unraveled. For example, recent literature has identified that ozone (O3) pulmonary responses have sex-specific effects. Work in several laboratories has shown that male and female mice exhibit different O3-induced airway hyperresponsiveness (AHR)(4) and that these effects are related to sex hormones (5, 6) or sex-dependent effects on the microbiome (7). Although modification of sex hormones represents an interesting experimental target, as a target strategy to reduce O3 health effects it may have limited appeal. Alternatively, the microbiome can be modified by diet, and therefore dietary modifications might be a viable strategy. In this issue of the Journal, Tashiro and colleagues (pp. 503–512) explore the effect of dietary modifications on pulmonary responses to acute O3 exposure (8). Using mice fed diets enriched in different types of dietary fiber (pectin and cellulose) or a fiberfree diet, they made several interesting observations that were sex dependent. In male mice, a pectin-enriched diet elicited a mild increase in O3-induced AHR at the highest methacholine dose, whereas a cellulose-enriched diet caused a pronounced reduction in AHR. In contrast, female mice exhibited augmented O3-induced AHR responses to both the pectin-and cellulose-enriched diets. A fiber-free diet did not impact O3-induced AHR in male mice. Contrary to what might be expected given their augmented responses to pectin and cellulose diets, female mice fed a fiber-free diet also exhibited enhanced AHR, similar to their responses to a fiber-enriched diet. These AHR effects appear to be largely dissociated from O3-induced injury or inflammatory effects, suggesting that in this model, injury was not driving the AHR responses. To explore potential mechanisms of the diet-and sexdependent AHR responses, the authors measured sex hormones and also gave the mice fed a fiber-free diet propionate to decrease short-chain fatty acids. Propionate administration did not alter AHR in females fed a fiber-free diet, and sex hormones did not associate with the sex-dependent diet phenotypes. Based on these findings, the authors evaluated sex-dependent, diet-induced changes in the microbiome to explain the observed phenotypes. Greater biodiversity and richness were found in the male mice fed a cellulose diet as compared with a pectin diet, and overall less effect was noted in the female mice fed either diet. However, the use of a fiber-free diet in female mice had a much greater effect on microbiome community structure. A statistical analysis to identify potential associations revealed that four taxa (Enterococcaceae, Lactobacillius, Blautia, and Streptococcaceae) associated with the observed sex differences in diet responses to O3-induced AHR. The data presented by Tashiro and colleagues build on a body of research, largely developed by this laboratory group, exploring the role of the microbiome in O3-induced pulmonary responses …