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母体摄入阿斯巴甜会通过激活核因子κB改变后代肺部Th1/Th2细胞因子平衡。

Maternal aspartame exposure alters lung Th1/Th2 cytokine balance in offspring through nuclear factor-κB activation.

作者信息

Chuang Hsiao-Chi, Yang Yu-Chen S H, Chou Hsiu-Chu, Chen Chung-Ming

机构信息

School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei, Taiwan; Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.

Joint Biobank, Office of Human Research, Taipei Medical University, Taipei, Taiwan.

出版信息

Int Immunopharmacol. 2025 Jan 3;145:113800. doi: 10.1016/j.intimp.2024.113800. Epub 2024 Dec 12.

Abstract

BACKGROUND

Epidemiological evidence suggests that maternal intake of nonnutritive sweeteners is positively associated with early childhood asthma incidence. We investigated the effects of maternal aspartame exposure during pregnancy and lactation on lung Th1/Th2 cytokine balance and intestinal microbiota in offspring and explored the mechanisms that mediate these effects.

METHOD

Pregnant BALB/c mice were randomly divided on gestational day 7 into two dietary intervention groups: control (drinking water only) and aspartame (drinking water +0.25 g/L aspartame) groups. The dams nursed their offspring for 3 weeks. On postnatal day 21, heart blood samples were collected, and immunoglobulin E levels were measured. Microorganisms from the lower gastrointestinal tract were sampled using a culture-independent approach. Lung tissues were harvested for biochemical analyses.

RESULTS

Maternal aspartame exposure increased the body weight of the dams from gestational day 7 to postnatal day 21 and the body weight of the offspring from birth to postnatal day 21. Maternal aspartame exposure significantly increased the levels of Th2 cytokines (interleukin [IL]-4, IL-5, and IL-13) and IL-17 and immunoglobulin E but reduced that of a Th1 cytokine (interferon-γ) in the offspring's lung tissues. The altered Th1/Th2 balance was accompanied by increased lung nuclear factor-κB activation. The bacterial composition and alpha-diversity of the gut microbiota of the offspring did not differ significantly between the control and aspartame groups.

CONCLUSION

Our findings suggest maternal aspartame exposure influences lung Th1/Th2 cytokine balance in offspring through nuclear factor-κB activation.

摘要

背景

流行病学证据表明,母亲摄入非营养性甜味剂与幼儿哮喘发病率呈正相关。我们研究了孕期和哺乳期母亲接触阿斯巴甜对后代肺部Th1/Th2细胞因子平衡和肠道微生物群的影响,并探讨了介导这些影响的机制。

方法

将妊娠第7天的BALB/c孕鼠随机分为两个饮食干预组:对照组(仅饮用蒸馏水)和阿斯巴甜组(饮用含0.25 g/L阿斯巴甜的蒸馏水)。母鼠哺育后代3周。在出生后第21天,采集心脏血液样本并测量免疫球蛋白E水平。采用非培养方法对下消化道微生物进行采样。采集肺组织进行生化分析。

结果

孕期接触阿斯巴甜的母鼠从妊娠第7天到出生后第21天体重增加,其后代从出生到出生后第21天体重增加。孕期接触阿斯巴甜显著增加了后代肺组织中Th2细胞因子(白细胞介素[IL]-4、IL-5和IL-13)、IL-17和免疫球蛋白E的水平,但降低了Th1细胞因子(干扰素-γ)的水平。Th1/Th2平衡的改变伴随着肺组织中核因子-κB激活增加。对照组和阿斯巴甜组后代肠道微生物群的细菌组成和α多样性没有显著差异。

结论

我们的研究结果表明,孕期接触阿斯巴甜的母亲通过激活核因子-κB影响后代肺部Th1/Th2细胞因子平衡。

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