阿斯巴甜对小鼠肠道屏障和肠道菌群的影响

摘要/Abstract

摘要：

目的运用人工合成甜味剂阿斯巴甜对小鼠进行干预，探讨其对小鼠肠道屏障和肠道菌群的影响，为添加剂的健康影响提供依据。方法将雄性C57BL/6J小鼠分为对照（Ctrl）组和阿斯巴甜（Asp）组，每组10只。Asp组按80 mg/（kg·d）进行灌胃，Ctrl组给予等量蒸馏水，每天1次，2个月后，通过HE染色检测小鼠结肠组织病理学变化。运用Western blot检测小鼠结肠组织紧密连接蛋白表达水平，包括闭合蛋白（occludin）和闭锁小带蛋白-1（zonula occludens-1，ZO-1）。采用16S rRNA高通量基因测序分析阿斯巴甜对小鼠肠道菌群的影响。结果 HE染色结果显示，Asp组小鼠结肠组织可见糜烂、黏膜上皮不完整及少量结缔组织增生，伴散在的粒细胞浸润；少量黏膜上皮细胞水样变性、细胞肿胀。Western blot检测结果显示，与Ctrl组比较，Asp组小鼠结肠组织occludin和ZO-1表达水平降低。肠道菌群分析结果表明，阿斯巴甜降低了小鼠肠道菌群α-多样性和β-多样性；在门水平上，与Ctrl组相比，Asp组小鼠Actinobacteriota（放线菌门）相对丰度升高，Verrucomicrobiota（疣微菌门）相对丰度降低；在科水平上，Asp组小鼠Streptococcaceae（链球菌科）相对丰度升高，Clostridia_UCG-014（梭菌UCG-014）、Akkermansiaceae（阿克曼菌科）、Ruminococcaceae_UCG-010（瘤胃球菌科_UCG-010）等相对丰度降低；在属水平上，Asp组小鼠肠道Peptostreptococcaceae相对丰度升高（肽链链球菌），Clostridia_UCG-014、Akkermansia（厚壁菌）、Ruminococcaceae_UCG-010等相对丰度降低；Asp组小鼠肠道菌群健康指数降低、肠道菌群失调指数升高。结论阿斯巴甜可导致小鼠肠道屏障损伤，改变肠道菌群。

关键词: 阿斯巴甜, 肠道屏障, 肠道菌群, 紧密连接蛋白, 肠道菌群健康指数, 肠道菌群失调指数

Abstract:

Objective To intervene in mice with artificially synthesized sweetener aspartame，explore its effects on the intestinal barrier and intestinal microflora of mice，and provide a basis for the health effects of additives. Methods The mice were randomly divided into a solvent control（Ctrl） group and an aspartame（Asp） group，with 10 mice in each group. Asp group mice were administered orally at a dose of 80 mg/（kg·d），while Ctrl group mice were given an equal amount of distilled water once a day. After 2 months，HE staining was used to detect the pathological changes in mouse colon tissues. Western blot was used to detect the expression levels of tight junction proteins in mouse colon tissue，including occludin and ZO-1.The effects of aspartame on mouse intestinal microflora were analyzed using high-throughput sequencing of the 16S rRNA gene. Results The HE staining results showed that the colon tissue of Asp group mice showed erosion，incomplete mucosal epithelium，and a small amount of connective tissue proliferation，accompanied by scattered granulocyte infiltration，and a small amount of mucosal epithelial cell watery degeneration，and swelling of mucosal epithelial cells. The results of Western blot showed that compared with the Ctrl group，the expression levels of occludin and ZO-1 in the Asp group mice were reduced. The analysis of gut microbiota showed that aspartame reduced the α-diversity and β-diversity of gut microbiota. At the phylum level，compared with the Ctrl group，the relative abundance of Actinobacteriota in the Asp group mice increased，while the relative abundance of Verrucomimicrobiota decreased. At the family level，the relative abundance of Streptococcaceae increased in the Asp group mice，while the relative abundance of Clostridia_UCG-014，Akkermansiaceae，and Ruminococcaceae_UCG-010 decreased. At the genus level，the relative abundance of Peptostreptococcaceae in the intestines of Asp group mice increased，while the relative abundance of Clostridi_UCG-014，Akkermansia，and Ruminococcaceae_UCG-010 decreased. Compared with the Ctrl group，the Asp group mice showed a decrease in the gut microbiota health index and an increase in the gut microbiota dysbiosis index. Conclusion Aspartame can cause damage to the intestinal barrier，and alter the intestinal microflora.

Key words: Aspartame, Intestinal barrier, Intestinal microflora, Tight junction proteins, Gut microbiota health index, Gut microbiota dysbiosis index

中图分类号:

R-332

潘神奕, 孙威, 鲁晶晶, 王丹华, 江阿沛. 阿斯巴甜对小鼠肠道屏障和肠道菌群的影响. [J]职业与健康, 2026, 42(17): 2343-2348.

PAN Shenyi, SUN Wei, LU Jingjing, WANG Danhua, JIANG Apei. Effects of aspartame on intestinal barrier and intestinal microflora in mice. [J]OCCUPATION AND HEALTH, 2026, 42(17): 2343-2348.

图/表 9

图1 各组小鼠结肠组织HE染色结果注：Ctrl—对照组；Asp—阿斯巴甜组；A—Ctrl组结肠组织病理形态（HE染色，40×）；B—Asp组结肠组织病理形态（HE染色，40×）；C—Ctrl组结肠组织病理形态（HE染色，200×）；D—Asp组结肠组织病理形态（HE染色，200×）。

图2 紧密连接蛋白occludin和ZO-1表达注：Ctrl—对照组；Asp—阿斯巴甜组；Occludin—闭合蛋白；ZO-1—闭锁小带蛋白-1；A—Occludin和ZO-1蛋白表达结果（n=3）；B—Occludin表达平均光密度值分析结果（n=6）；C—ZO-1表达平均光密度值分析结果（n=6）；aP<0.05。

图3 肠道菌群α-多样性指数分析注：Ctrl—对照组；Asp—阿斯巴甜组；NS—差异无统计学意义（n=10）。

图4 肠道菌群β-多样性分析注：Ctrl—对照组；Asp—阿斯巴甜组；A—主坐标分析结果；B—非度量多维尺度分析结果（n=10）。

图5 阿斯巴甜对肠道菌群门水平组成的影响注：Ctrl—对照组；Asp—阿斯巴甜组；aP<0.05；bP<0.01（n=10）。

图6 阿斯巴甜对肠道菌群科水平组成的影响注：Ctrl—对照组；Asp—阿斯巴甜组；aP<0.05；bP<0.01（n=10）。

图7 阿斯巴甜对肠道菌群属水平组成的影响注：Ctrl—对照组；Asp—阿斯巴甜组；aP<0.05；bP<0.01（n=10）。

图8 阿斯巴甜对小鼠肠道微生物组健康指数的影响注：Ctrl—对照组；Asp—阿斯巴甜组；aP<0.05（n=10）。

图9 阿斯巴甜对小鼠肠道菌群失调指数的影响注：Ctrl—对照组；Asp—阿斯巴甜组；aP<0.05（n=10）。

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