Low Dose of Sucralose Alter Gut Microbiome in Mice - PubMed (original) (raw)

Low Dose of Sucralose Alter Gut Microbiome in Mice

Zibin Zheng et al. Front Nutr. 2022.

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.

Keywords: gut microbiome; intestinal barrier; low dose; mice; sucralose.

Copyright © 2022 Zheng, Xiao, Ma, Lyu, Peng, Wang, Ren and Li.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1

Figure 1

Bar chart showing the mice body weight (A) and liver weight (B). Representative H&E-stained sections from jejunum, ileum, cecum and colon (C), the arrowhead points in the direction where lymphocyte aggregation. Histopathological scores of the H&E staining (D). Data was expressed as mean ± SEM (n = 8) and analyzed by one-way ANOVA analysis. The different superscript letters on the histogram represent a significant difference (D) (P < 0.01).

Figure 2

Figure 2

Alpha diversity including Shannon index (A,C,E,G) and the number of features (B,D,F,H) in control group, Trichlorogalactosucrose (TGS) 1–4 (T1, T2, T3, T4) groups in jejunum (A,B), ileum (C,D), cecum (E,F), colon (G,H). Data was processed through log10, and expressed as mean ± SEM (n = 8) and analyzed by one-way ANOVA analysis. The different superscript letters on the boxplot represent a significant difference (P < 0.01).

Figure 3

Figure 3

PCA of the mice gut microbial community composition of the Control and T1-4 group based on the Bray-Curtis distances showed distinct clusters, _P_-value and _R_-value were calculated by ANOSIM. The jejunum (A), ileum (B), cecum (C), and colon (D) microbial community structure between the Control group and T1–4 groups were differentiated by colors (red, brown, green, blue, purple, respectively).

Figure 4

Figure 4

Phylogenetic tree analysis showing top 129 bacterial taxa based on 16S rRNA gene V4-V5 hypervariable regions, after removing 21 features which were uncultured or no rank in genus level. The innermost clades and labels were colored by genus.

Figure 5

Figure 5

The top 30 features in Control group and T1–4 groups of jejunum, ileum, cecum and colon microbiome in mice. Each color indicates the relative abundance of a bacterial taxon on the bar chart.

Figure 6

Figure 6

Heat map indicated 68 bacterial taxa were identified by LEfSe (LDA > 3) in mice jejunum (n = 20) (A), ileum (n = 11) (C), cecum (n = 20) (B), and colon (n = 17) (D) microbiome. The top 1,000 features were used for LEfSe analysis. Heat map shows the average relative abundances on a Z-score.

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