Long-term consumption of the sugar substitute sorbitol alters gut microbiome and induces glucose intolerance in mice

Aims: Epidemic obesity and diabetes have led to increased use of low-calorie sweeteners. Although several studies have suggested that consumption of artificial sweeteners, such as aspartame and saccharin, might have negative effects, the potential impacts of natural sweeteners on human health remain largely unknown. Main methods: The deferential effects of short term and long term consumption of sorbitol on glucose homeostasis in mice by oral gavage. The glucose homeostasis and utility were evaluated by both oral or intraperitoneal glucose tolerance tests. Insulin levels were determined using enzyme-linked immunosorbent assay. Changes of gut microbiome were evaluated by 16S rRNA gene sequencing, and analyzed by principal components analysis. Key findings: Bolus feeding of sorbitol by gavage significantly increased plasma insulin concentrations and decreased fasting blood glucose levels. Intriguingly, long-term sorbitol gavage for four weeks showed no significant effects on intraperitoneal glucose tolerance test outcomes, but it induced glucose intolerance according to the oral glucose tolerance test. Thus, we tested whether long-term sorbitol gavage might alter the relative abundances of gut microbiome constituents in mice. Principal components analysis indicated that long-term sorbitol intake indeed caused significant changes to the gut microbiome. In particular, we found that long-term sorbitol intake significantly decreased the relative abundances of Bifidobacterium, Lachnospiraceae UCG 001, Lachnospiraceae NK4A136, Eubacterium ventriosum, Candidatus Arthromitus, and Ruminococcus torques. We also found that long-term sorbitol increased the relative abundances of Helicobacter, Tyzzerella, Alistipes, and Prevotella 9. Significance: Long-term sorbitol consumption may change the composition of the gut microbiome and potentially induce glucose intolerance.