Gut Microbiome Response to Sucralose and Its Potential Role in Inducing Liver Inflammation in Mice

Abstract

Sucralose is the most widely used artificial sweetener, and its health effects have been highly debated over the years. In particular, previous studies have shown that sucralose consumption can alter the gut microbiota. The gut microbiome plays a key role in processes related to host health, such as food digestion and fermentation, immune cell development, and enteric nervous system regulation. Inflammation is one of the most common effects associated with gut microbiome dysbiosis, which has been linked to a series of human diseases, such as diabetes and obesity. The aim of this study was to investigate the structural and functional effects of sucralose on the gut microbiota and associated inflammation in the host. In this study, C57BL/6 male mice received sucralose in their drinking water for 6 months. The difference in gut microbiota composition and metabolites between control and sucralose-treated mice was determined using 16S rRNA gene sequencing, functional gene enrichment analysis and metabolomics. Inflammatory gene expression in tissues was analyzed by RT-PCR. Alterations in bacterial genera showed that sucralose affects the gut microbiota and its developmental dynamics. Enrichment of bacterial pro-inflammatory genes and disruption in fecal metabolites suggest that 6-month sucralose consumption at the human acceptable daily intake (ADI) may increase the risk of developing tissue inflammation by disrupting the gut microbiota, which is supported by elevated pro-inflammatory gene expression in the liver of sucralose-treated mice. Our results highlight the role of sucralose-gut microbiome interaction in regulating host health-related processes, particularly chronic inflammation.

Low intake of digestible carbohydrates ameliorates duodenal absorption of carbohydrates in mice with glucose metabolism disorders induced by artificial sweeteners

“…In the present study, we aimed to explore the efficacy of reducing the concentration of digestible carbohydrates, an important component of the human diet, on biochemical parameters in a mouse model of glucose metabolism disorders. In line with previous studies, our findings demonstrated that animals who consumed artificial sweeteners showed many characteristics of metabolic syndrome, such as increased body weight, insulin resistance, high‐level gene expression of sweet taste receptors and transporters, and reduced glucose tolerance …”

“…In line with previous studies, our findings demonstrated that animals who consumed artificial sweeteners showed many characteristics of metabolic syndrome, such as increased body weight, insulin resistance, high-level gene expression of sweet taste receptors and transporters, and reduced glucose tolerance. [35][36][37] However, it was reported that mice with 1.5 and 15 mg kg −1 sucralose administration for 8 weeks did not show significant weight gain compared with mice not exposed to sucralose. 15 There are some hypotheses that might explain the contradiction: (i) researches on same sweetener with different concentrations; (ii) sweetener with the same concentration provide different sweetness for animals or humans.…”

Dietary Exposures to Common Emulsifiers and Their Impact on the Gut Microbiota: Is There a Cause for Concern?

“…Another recent study suggests that conventional cleaners and eco-friendly cleaners modulate the composition of the gut microbiota of infants leading to obesity at 3 years of age (Tun, Tun, & Mahoney et al, 2018). Likewise, exposure to artificial sweeteners (sucralose, acesulfame potassium, saccharin) has been associated with an altered gut microbiota and, ultimately, gut and intestinal inflammation, obesity, and diabetes (Bian et al, 2017a(Bian et al, , 2017bSuez, Korem, Zilberman-Schapira, Segal, & Elinav, 2015). Evidently there is a clear pattern in that the composition of the gut microbiota is shifted in different disease states; however, the exact mechanism by which this occurs remain unknown.…”

The Western Diet–Microbiome-Host Interaction and Its Role in Metabolic Disease

“…These sweeteners have also not been tested for effects on the gut microbiota prior to approval. Effects from rodent studies include altered composition of microbes leading to impaired glucose tolerance [28,59,60], as well as increased pro-inflammatory potential [61,62] and liver inflammation [61]. NAS-induced alterations in microbiota composition leading to adverse metabolic outcomes should give rise to concern, especially because the demand for NAS containing products are increasing, and persons suffering from metabolic disorders could be more likely to choose such products for health benefits.…”