Low Dose of Sucralose Alter Gut Microbiome in Mice.

Zibin Zheng,Hao Peng,Jinjun Li,Lingyan Ma,Wentao Lyu,Ying Ren,Xiaorong Wang,Yingping Xiao

doi:10.3389/fnut.2022.848392

Zibin Zheng, Hao Peng + Show 6 more

Open Access

https://doi.org/10.3389/fnut.2022.848392

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Abstract

Sucralose is a non-nutritive artificial sweetener (NNS) used in foods or beverages to control blood glucose levels and body weight gain. The consumption of NNS has increased in recent years over the world, and many researches have indicated long-term sucralose administration altered the gut microbiome composition of mice. These studies all focus on the US Food and Drug Administration (FDA) defined acceptable daily intake (ADI), approximately 5 mg/kg BW/day for human. In our study, mice were given with T1-4 (0.0003, 0.003, 0.03, and 0.3 mg/mL) of sucralose, respectively, Control group mice were given normal water. In particular, 0.3 mg/mL of sucralose was equal to the ADI (5 mg/kg BW/day). After 16 weeks, all mice were weighted and sacrificed, the liver of each mouse was isolated and weighed, segments of jejunum, ileum and colon were collected for H&E-stained. The contents of jejunum, ileum, cecum and colon were collected for 16S rRNA gene sequencing. The results showed sucralose administration affects the intestinal barrier function evidenced by distinct lymphocyte aggregation in ileum and colon while not change the mice body weight. The 16S rRNA gene sequencing of the mice gut microbiome suggested sucralose administration significantly changed the composition of gut microbiota, especially in T1 and T4 group. For example, a reduction of probiotics abundance (Lachnoclostridium and Lachnospiraceae) was found in cecum of T4 group mice compared with Control group. On the other hand, Allobaculum, which was reported positively correlated with diabetes, was increased in the T1 and T4 group. In addition, the potential pathogens, including Tenacibaculum, Ruegeria, Staphylococcus were also increased in jejunum, ileum and colon by sucralose administration in T1 and T4 group. These new findings indicate that low dose of sucralose (T1) alter gut microbiome in mice, and these adverse health effects are equal to ADI level (T4). Overall, our study provides guidance and suggestions for the use of sucralose in foods and beverages.

Highlights

In order to confirm the effect of zero-calorie sucralose on body nutritional absorption, Mice was given with T1-4 (0.0003, 0.003, 0.03, and 0.3 mg/mL) of sucralose in drinking water, respectively
Sucralose administration induced lymphocyte aggregation, which may lead to the increase of inflammatory factors. These revealed that sucralose administration might disrupt intestinal barrier function, the sucralose concentration and the effect on intestinal barrier of these studies all consistent with T4 group in our study, more interestingly, we found the intestinal barrier was significantly damaged in group T1
We demonstrate low dose of sucralose alter gut microbiome in mice by using 16S rRNA gene sequencing, T1-4 groups mice accessed 0.0003 g/mL, 0.003 mg/mL, 0.03 mg/mL, 0.3 mg/mL sucralose for 16 weeks, 0.1 mg/ml of sucralose solution was Food and Drug Administration (FDA) acceptable daily intake [18]

Summary

Introduction

Non-nutritional sweeteners (NNS) added to beverages and foods are defined as sweetener with higher sweetness and lower calorie content than caloric or nutritional sweeteners (such as sucrose or corn syrup) [1]. Sucralose named trichlorogalactosucrose and TGS, is a NNS, zero-calorie artificial. It is a substitute for chlorinated sugar, and its sweetness is 600 times than sucrose, because of its low production cost, high thermal stability and solubility, sucralose has become an important sugar substitute in foods and beverage [3, 4]. Researches have confirmed that sucralose can change the composition of gut microbiome, inhibiting intestinal development, and aggravating HFD-induced hepatic steatosis in adulthood [5, 9]

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