The Evolution & Medicine Review

For decades food manufacturers have marketed saccharin, along with other non-caloric artificial sweeteners (NAS), as healthy alternatives to sugar. Artificial sugar substitutes cannot be digested by humans and have been recommended for patients with diabetes  and for those trying to lose weight. However, a new report in the journal Nature suggests that NAS are harmful to metabolic health. In this study, saccharin given to mice and to healthy human subjects worsened glucose control compared to sugar, and had the paradoxical effect of increasing blood glucose levels.

Saccharin increased blood glucose in mice (Suez et al. doi:10.1038/nature13793)

Lead investigator Eran Elinov and his colleagues showed that the intestinal microbiota was responsible for the adverse metabolic effects of saccharin. Saccharin increased numbers of Bacteroides bacteria in the gut and also increased the density of bacteria in the Enterobacteriaceae group while decreasing the number of certain beneficial bacteria, such as Akkermansia mucinophila. Remarkably when fecal bacteria from saccharin-fed humans were transferred to germ-free mice, the mice became glucose intolerant, similar to their human donors. Some human subjects were non-responders, maintaining normal metabolism of glucose after exposure to saccharin. Fecal samples from non-responders were inoculated into germ free mice without causing glucose intolerance. These findings indicate a causal role for the microbiota in the impairment of metabolism by artificial sweeteners.

This study did not identify the precise mechanism by which microbiota alter metabolism, but saccharin caused functional changes in the microbiome, including increased microbial production of the short chain fatty acids propionate and acetate. These short chain fatty acids are also elevated in obesity, and might promote weight gain by increasing energy harvest from the diet.  Short chain fatty acids and other microbial products also affect metabolism and brain activity by affecting neural circuits that link the gut to the brain, also known as the gut-brain axis.

Athena Aktipis, Carlo Maley, and I recently reviewed neural and other mechanisms by which microbes potentially manipulate eating behavior; read more here. We proposed that the differing fitness interests in the metagenome (the collection of host and microbial genes) might drive eating behaviors that lead to obesity.  Whether gut microbes trigger changes in brain activity after exposure to artificial sweeteners is unknown and was not addressed in Elinov’s study. On the other hand, microbial control of metabolism, as demonstrated by Elinov and colleagues, is another potential area of genetic conflict between microbes and the host. How microbes interact with different nutrients and with the host to cause glucose intolerance is a ripe area for further study.

Read more:

Suez, J. et al. “Artificial sweeteners induce glucose intolerance by altering the gut microbiota.” Nature (2014). (not open access)

An open access editorial accompanying the Nature article is here.