There's something in the air: disentangling the role of airborne microbes and pollutants in the inflammatory response of asthma along a latitudinal gradient in Canada

空气中弥漫着某种东西：沿着加拿大的纬度梯度，理清空气中的微生物和污染物在哮喘炎症反应中的作用

• 批准号: 571457-2021
• 负责人: Girard, Catherine
• 金额: $ 2.88万
• 依托单位: Université du Québec à Chicoutimi
• 依托单位国家: 加拿大
• 项目类别: Alliance Grants
• 财政年份: 2021
• 资助国家: 加拿大
• 起止时间: 2021-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=729167
• 关键词: There; something; air; disentangling; role

Asthma is an inflammatory respiratory disease that affects over 3.8 million Canadians, approximately a quarter of which are children. Few studies have investigated the morbidity of asthma in Northern Canada, but Inuit children have been found to have lower prevalence of asthma compared to other Indigenous and non-Indigenous children. This is interesting because asthma is not only influenced by genetics but also by environmental factors. Therefore, where an individual lives has a significant impact on the risk of developing asthma and its severity. This can be due to exposure to allergens but also to other protective or inflammatory processes. For example, recent studies have found that growing up in areas with diverse microbial communities such as farmland can decrease the likelihood of developing asthma, by helping human-associated microbes (the microbiome) train the immune system. More directly, certain airborne microorganisms have been found to have a protective role against the development of asthma by preventing serious inflammation of the airways. Microorganisms are not the only aspect of air quality that can contribute to asthma. Pollutants associated with resource extraction, transportation, as well as consumer and commercial products can have the opposite effect and induce inflammation and oxidative damage to the airways thus contributing to severity of symptoms. Airborne environmental microbes and pollutants therefore have opposite effects in asthma, and these factors are highly specific to where a person lives. However, it is unclear how these two variables intersect, and how together they may promote or impede the presentation of asthma. Our goal is to investigate how air quality may contribute to inflammation and asthma in an in vitro co-culture cell model of the human respiratory tract. We will sample 4 regions along a gradient varying in population size, but also in vegetation and land use: Scarborough (Ontario, population ~632k), Saguenay (Quebec, ~69k), Kuujjuarapik (Nunavik, ~686) and Resolute Bay (Nunavut, ~198). At all sites, we will measure air pollutants (volatile organic compounds, trace elements, particulate matter), pollen, and microbial communities for characterization through metagenomic sequencing. Airborne microbes will also be collected and concentrated from each site. In the lab, we will expose a co-culture cellular model of the human respiratory airway to these field microbes. The co-culture will also be exposed to varying concentrations of pollutants, representative of our field data. We will then measure indicators of oxidative stress and inflammation, to quantify the role of both microbes and pollutants in asthma and identify organisms that protect from inflammation. We hypothesize that the diversity of airborne microbes in an environment will have a protective effect in our northern sites, which decreases closer to the treeline. We also expect airborne pollutant levels representative of our Northern sites to induce less inflammation. This study proposes to use a novel approach to understand how the environment shapes the etiology of asthma. Our mechanistic approach will allow us to disentangle the role of the major environmental variables in inflammation of respiratory airways, and to identify the drivers of asthma along a latitudinal gradient in Canada.

哮喘是一种炎症性呼吸道疾病，影响着超过380万加拿大人，其中约四分之一是儿童。很少有研究调查加拿大北部哮喘的发病率，但因纽特儿童被发现与其他土著和非土著儿童相比，哮喘发病率较低。这很有趣，因为哮喘不仅受遗传因素的影响，还受环境因素的影响。因此，一个人生活在哪里对患哮喘的风险及其严重程度有重大影响。这可能是由于接触过敏原，但也可能是由于其他保护性或炎症过程。例如，最近的研究发现，在农田等微生物群落多样的地区长大，可以帮助人类相关微生物(微生物群)训练免疫系统，从而降低患哮喘的可能性。更直接的是，某些空气中的微生物被发现通过防止严重的呼吸道炎症来预防哮喘的发展。微生物并不是空气质量中唯一会导致哮喘的因素。与资源开采、运输以及消费和商业产品相关的污染物可能会产生相反的影响，导致呼吸道发炎和氧化损伤，从而加剧症状的严重性。因此，空气中的环境微生物和污染物对哮喘有相反的影响，这些因素与人的居住地高度相关。然而，目前尚不清楚这两个变量是如何相交的，以及它们如何共同促进或阻碍哮喘的出现。我们的目标是在体外共培养的人类呼吸道细胞模型中研究空气质量如何导致炎症和哮喘。我们将沿着梯度抽样4个地区，这些地区不仅人口规模不同，而且植被和土地利用也不同：斯卡伯勒(安大略省，人口~632k)，萨盖内(魁北克，~69k)，Kuujjuarapik(努纳维克，~686)和决心湾(努纳武特，~198)。在所有地点，我们将测量空气污染物(挥发性有机化合物、微量元素、颗粒物)、花粉和微生物群落，以通过元基因组测序进行表征。空气中的微生物也将从每个地点收集和集中。在实验室中，我们将向这些野外微生物展示人类呼吸道的共培养细胞模型。联合培养也将暴露在不同浓度的污染物中，这代表了我们的现场数据。然后，我们将测量氧化应激和炎症的指标，以量化微生物和污染物在哮喘中的作用，并确定保护机体免受炎症的影响。我们假设，环境中空气中微生物的多样性将在我们的北部地点产生保护作用，而北部地点的保护作用会在靠近树线的地方减少。我们还预计，代表我们北方站点的空气污染物水平将导致较少的炎症。这项研究建议使用一种新的方法来理解环境如何塑造哮喘的病因。我们的机械方法将使我们能够理清主要环境变量在呼吸道炎症中的作用，并沿着加拿大的纬度梯度确定哮喘的驱动因素。