高盐饮食对人类和小鼠哮喘的影响：对特定T细胞特征和微生物组的影响
2024/07/30
摘要
背景：哮喘发病率的上升与包括饮食习惯在内的各种环境和生活方式因素有关。膳食中的盐是否会导致哮喘发病率的上升仍存在争议。我们旨在研究较高的盐摄入量对人类哮喘发病率的影响，并利用小鼠模型评估其潜在机制。
方法：利用英国生物库资源进行流行病学研究。从42,976名有过敏史的参与者那里获得了数据。通过定点尿液估算24小时钠排泄量，并通过Cox回归评估其与哮喘发病率的关系，同时调整相关协变量。在机理研究方面，采用高盐饮食（HSD）或正常盐饮食喂养的屋尘螨诱发的过敏性气道炎症（AAI）小鼠模型来描述疾病的发展。通过基于16S rRNA基因的代谢编码方法分析了肺部和粪便（作为肠道的代表）的微生物组。
结果：在人类中，尿钠排泄量与雌性哮喘发病率直接相关，但与雄性哮喘发病率无关。喂食HSD的雌性小鼠显示出加重的AAI，其特征是总IgE水平升高、TH2-TH17型炎症细胞浸润以及渗透压敏感基因上调。HSD会诱导血清短链脂肪酸以及肠道和肺部微生物组发生明显变化，肠道中的类杆菌与固醇菌比例降低，乳酸杆菌相对丰度下降，而肺部则富集了伽马蛋白菌。
结论：在有过敏史的成年女性中，高膳食盐摄入量与哮喘发病率相关。雌性小鼠显示出HSD诱导的T细胞肺特征，同时伴随着肠道和肺部微生物组的改变。
The impact of high-salt diet on asthma in humans and mice: Effect on specific T-cell signatures and microbiome
S. Musiol, C. P. Harris, S. Gschwendtner, A. Burrell, Y. Amar, B. Schnautz, et al.
Abstract
BACKGROUND:The rise in asthma has been linked to different environmental and lifestyle factors including dietary habits. Whether dietary salt contributes to asthma incidence, remains controversial. We aimed to investigate the impact of higher salt intake on asthma incidence in humans and to evaluate underlying mechanisms using mouse models.
METHODS:Epidemiological research was conducted using the UK Biobank Resource. Data were obtained from 42,976 participants with a history of allergies. 24-h sodium excretion was estimated from spot urine, and its association with asthma incidence was assessed by Cox regression, adjusting for relevant covariates. For mechanistic studies, a mouse model of mite-induced allergic airway inflammation (AAI) fed with high-salt diet (HSD) or normal-salt chow was used to characterize disease development. The microbiome of lung and feces (as proxy for gut) was analyzed via 16S rRNA gene based metabarcoding approach.
RESULTS:In humans, urinary sodium excretion was directly associated with asthma incidence among females but not among males. HSD-fed female mice displayed an aggravated AAI characterized by increased levels of total IgE, a TH2-TH17-biased inflammatory cell infiltration accompanied by upregulation of osmosensitive stress genes. HSD induced distinct changes in serum short chain fatty acids and in both gut and lung microbiome, with a lower Bacteroidetes to Firmicutes ratio and decreased Lactobacillus relative abundance in the gut, and enriched members of Gammaproteobacteria in the lung.
CONCLUSIONS:High dietary salt consumption correlates with asthma incidence in female adults with a history of allergies. Female mice revealed HSD-induced T-cell lung profiles accompanied by alterations of gut and lung microbiome.
背景：哮喘发病率的上升与包括饮食习惯在内的各种环境和生活方式因素有关。膳食中的盐是否会导致哮喘发病率的上升仍存在争议。我们旨在研究较高的盐摄入量对人类哮喘发病率的影响，并利用小鼠模型评估其潜在机制。
方法：利用英国生物库资源进行流行病学研究。从42,976名有过敏史的参与者那里获得了数据。通过定点尿液估算24小时钠排泄量，并通过Cox回归评估其与哮喘发病率的关系，同时调整相关协变量。在机理研究方面，采用高盐饮食（HSD）或正常盐饮食喂养的屋尘螨诱发的过敏性气道炎症（AAI）小鼠模型来描述疾病的发展。通过基于16S rRNA基因的代谢编码方法分析了肺部和粪便（作为肠道的代表）的微生物组。
结果：在人类中，尿钠排泄量与雌性哮喘发病率直接相关，但与雄性哮喘发病率无关。喂食HSD的雌性小鼠显示出加重的AAI，其特征是总IgE水平升高、TH2-TH17型炎症细胞浸润以及渗透压敏感基因上调。HSD会诱导血清短链脂肪酸以及肠道和肺部微生物组发生明显变化，肠道中的类杆菌与固醇菌比例降低，乳酸杆菌相对丰度下降，而肺部则富集了伽马蛋白菌。
结论：在有过敏史的成年女性中，高膳食盐摄入量与哮喘发病率相关。雌性小鼠显示出HSD诱导的T细胞肺特征，同时伴随着肠道和肺部微生物组的改变。
（中日友好医院呼吸与危重症医学科 李春晓 摘译 林江涛 审校）
（Allergy. 2024 Jul;79(7):1844-1857. doi: 10.1111/all.16148. Epub 2024 May 26.）
（Allergy. 2024 Jul;79(7):1844-1857. doi: 10.1111/all.16148. Epub 2024 May 26.）
The impact of high-salt diet on asthma in humans and mice: Effect on specific T-cell signatures and microbiome
S. Musiol, C. P. Harris, S. Gschwendtner, A. Burrell, Y. Amar, B. Schnautz, et al.
Abstract
BACKGROUND:The rise in asthma has been linked to different environmental and lifestyle factors including dietary habits. Whether dietary salt contributes to asthma incidence, remains controversial. We aimed to investigate the impact of higher salt intake on asthma incidence in humans and to evaluate underlying mechanisms using mouse models.
METHODS:Epidemiological research was conducted using the UK Biobank Resource. Data were obtained from 42,976 participants with a history of allergies. 24-h sodium excretion was estimated from spot urine, and its association with asthma incidence was assessed by Cox regression, adjusting for relevant covariates. For mechanistic studies, a mouse model of mite-induced allergic airway inflammation (AAI) fed with high-salt diet (HSD) or normal-salt chow was used to characterize disease development. The microbiome of lung and feces (as proxy for gut) was analyzed via 16S rRNA gene based metabarcoding approach.
RESULTS:In humans, urinary sodium excretion was directly associated with asthma incidence among females but not among males. HSD-fed female mice displayed an aggravated AAI characterized by increased levels of total IgE, a TH2-TH17-biased inflammatory cell infiltration accompanied by upregulation of osmosensitive stress genes. HSD induced distinct changes in serum short chain fatty acids and in both gut and lung microbiome, with a lower Bacteroidetes to Firmicutes ratio and decreased Lactobacillus relative abundance in the gut, and enriched members of Gammaproteobacteria in the lung.
CONCLUSIONS:High dietary salt consumption correlates with asthma incidence in female adults with a history of allergies. Female mice revealed HSD-induced T-cell lung profiles accompanied by alterations of gut and lung microbiome.
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