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. 2017 Sep;107(Pt B):530-539.
doi: 10.1016/j.fct.2017.04.045. Epub 2017 May 1.

Saccharin induced liver inflammation in mice by altering the gut microbiota and its metabolic functions

Xiaoming Bian  1 , Pengcheng Tu  2 , Liang Chi  2 , Bei Gao  1 , Hongyu Ru  3 , Kun Lu  4
Affiliations

Saccharin induced liver inflammation in mice by altering the gut microbiota and its metabolic functions

Xiaoming Bian et al. Food Chem Toxicol. 2017 Sep.

Abstract

Maintaining the balance of the gut microbiota and its metabolic functions is vital for human health, however, this balance can be disrupted by various external factors including food additives. A range of food and beverages are sweetened by saccharin, which is generally considered to be safe despite controversial debates. However, recent studies indicated that saccharin perturbed the gut microbiota. Inflammation is frequently associated with disruptions of the gut microbiota. The aim of this study is to investigate the relationship between host inflammation and perturbed gut microbiome by saccharin. C57BL/6J male mice were treated with saccharin in drinking water for six months. Q-PCR was used to detect inflammatory markers in mouse liver, while 16S rRNA gene sequencing and metabolomics were used to reveal changes of the gut microbiota and its metabolomic profiles. Elevated expression of pro-inflammatory iNOS and TNF-α in liver indicated that saccharin induced inflammation in mice. The altered gut bacterial genera, enriched orthologs of pathogen-associated molecular patterns, such as LPS and bacterial toxins, in concert with increased pro-inflammatory metabolites suggested that the saccharin-induced liver inflammation could be associated with the perturbation of the gut microbiota and its metabolic functions.

Keywords: Artificial sweetener; Gut microbiota; Inflammation; Metabolite; Saccharin.

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Figures

Figure 1
Figure 1
Comparisons of pro-inflammatory gene expression on mRNA level in liver of saccharin-treated mice. Inducible nitric-oxide synthase (iNOS) and tumor necrosis factor alpha (TNF-α) significantly elevated in liver of saccharin-treated mice. (*p<0.05)
Figure 2
Figure 2
Saccharin consumption altered the dynamics of gut microbiome development in male C57BL/6J mice. Anaerostipes (A) and Ruminococcus (B) were significantly decreased after three-month consumption; Ruminococcus (B), Adlercreutzia (C) and Dorea (D) were decreased after six-month consumption. Sporosarcina (E), Jeotgalicoccus (F), Akkermansia (G), Oscillospira (H) and Corynebacterium (I) were significantly increased after three-month consumption; Corynebacterium (I), Roseburia (J) and Turicibacter (K) were increased after six-month consumption. (*p<0.05, **p<0.01, ***p<0.001)
Figure 3
Figure 3
Significantly altered orthologs of the gut microbiota based on functional enrichment analysis. Genes of lipopolysaccharide (LPS) biosynthesis (A), flagellar assembly (B), fimbria (C), bacterial toxins (D), and multidrug resistance (E) were significantly increased in saccharin-treated mice (p<0.05).
Figure 4
Figure 4
(A). Saccharin consumption changed the fecal metabolome in male C57BL/6J mice. 1743 metabolic features were significantly (p<0.05 and fold change>1.5) changed compared to controls. (B). Fecal metabolic profiles of controls were separated from those of saccharin-treated mice by PLS-DA.
Figure 5
Figure 5
Saccharin consumption significantly altered key fecal metabolites in male C57BL/6J mice, as exemplified by equol, a gut microbiome-catalyzed metabolite of daidzein (A) and metabolites involved in mediating inflammation (B). (*p<0.05, **p<0.01, ***p<0.001)
Figure 6
Figure 6
The functional link between saccharin-induced gut microbiome perturbations and host inflammation.
See this image and copyright information in PMC

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