Gut microbiota mediates NAS-induced glucose intolerance in mice

Mouse groups consuming NAS in both lean and HFD states were treated with a gram-negative-targeting broad-spectrum antibiotic to test whether the gut microbiota may regulate the observed NAS effects. The antibiotics were ciprofloxacin and metronidazole (“antibiotics A”). A second antibiotic treatment with gram-positive-targeting antibiotic vancomycin (“antibiotics B”) was also conducted.
After four weeks of antibiotic treatment, the differences in glucose intolerance between NAS-drinking mice and the controls were abolished in both the lean and HFD-fed groups for both treatments. These results suggest that NAS-induced glucose intolerance may be mediated by the intestinal microbiota.
Faecal transplantation experiments were conducted to establish a causal relationship between glucose intolerance and the microbiota. The microbiota of lean mice drinking commercial saccharin or glucose (control) was transferred into lean mice that have never encountered saccharin in their diets.
Recipients of the microbiota from saccharin-drinking mice exhibited an impaired glucose tolerance response compared to recipients of the microbiota from control. Transfers of the microbiota composition of HFD-fed mice drinking saccharin also resulted in the same glucose intolerance phenotype.

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Figure 1: Blood glucose levels after intake of artificial sweeteners (saccharin, sucralose and aspartame) and controls (water, sucrose and glucose). Different treatments, with gram-negative-targeting antibiotics, and gram-positive-targeting antibiotics, and no antibiotics were used. The artificial sweetener treatments without antibiotic treatment show the highest glucose intolerance curves.
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Figure 2: Glycaemic response for each treatment. Artificial sweeteners without antibiotic treatment show abnormal glycaemic responses in comparison to controls and antibiotic-treated mice.

Reference: Suez, Jotham et al. ‘Artificial Sweeteners Induce Glucose Intolerance By Altering The Gut Microbiota’. Nature (2014)

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