How Artificial Sweeteners Induce Diabetes- and Obesity-Related Changes

How Artificial Sweeteners Induce Diabetes- and Obesity-Related Changes

A groundbreaking new study published in the prestigious journal Nature has revealed how non-caloric artificial sweeteners (NAS) drive obesity- and diabetes-related changes in both mice and humans.

The study titled, "Artificial sweeteners induce glucose intolerance by altering the gut microbiota," states:

"Here we demonstrate that consumption of commonly used NAS formulations drives the development of glucose intolerance through induction of compositional and functional alterations to the intestinal microbiota."

Part 1: Gut Bacteria Mediate Artificial Sweetener-Induced Blood Sugar Disturbances

The researchers administered commercially available formulations of saccharin (Sweet' N Low), sucralose (Splenda) or aspartame (Equal) in the drinking water of 10-week old mice. The control group received I either glucose or sucrose. After 11 weeks, the three artificial sweetener fed groups developed "marked glucose intolerance," with saccharin having the most deleterious effects followed by sucralose and aspartame. 

Gut changes linked to artificial sweeteners

Graph showing the effects of artificial sweeteners on blood glucose levels.

The researchers hypothesized that since artificial sweeteners pass through the gut mostly unabsorbed by the body that the microbiota may be responsible for regulating their observed adverse effects on blood sugar.  To test their theory they administered antibiotics to mice while keeping them on their diet and sweetener supplementation regimens. Their results indicate that gut bacteria indeed drive the adverse effects of these sweeteners:

"Notably, after 4 weeks of antibiotic treatment, differences in glucose intolerance between NAS-drinking mice and controls were abolished both in the lean and the obese states. Similar effects were observed with the Gram-positive-targeting antibiotic vancomycin ('antibiotics B', 0.5 g l−1). These results suggest that NAS-induced glucose intolerance is mediated through alterations to the commensal microbiota, with contributions from diverse bacterial taxa."

Finally, in order to test whether the role of microbiota in upsetting blood sugar balance was 'cause and effect' they performed a fecal transplant from mice receiving saccharin or glucose into germ-free mice receiving the same normal-chow diet.  Their results confirmed the crucial role of the microbiota in inducing blood sugar disturbing effects:

"Notably, recipients of microbiota from mice consuming commercial saccharin exhibited impaired glucose tolerance as compared to control (glucose) microbiota recipients, determined 6 days following transfer. Transferring the microbiota composition of HFD-consuming mice drinking water or pure saccharin replicated the glucose intolerance phenotype. Together, these results establish that the metabolic derangements induced by NAS consumption are mediated by the intestinal microbiota."

Artificial Sweeteners Induce Negative Changes In Gut Bacteria 

The researchers next performed an analysis of the changes induced in the composition of microbiota by saccharin finding a widespread reorganization:

 "Compared to all control groups, the microbiota of saccharin-consuming mice displayed considerable dysbiosis, with more than 40 operational taxonomic units (OTUs) significantly altered in abundance ."

Notably, the researchers found that many of the strains that were increased in relative abundance belonged to the Bacteroides genus and Clostridiales order, both of which contain members linked to obesity and opportunistic infections.  They also observed that these microbiota changes lead to 1) increased lipopolysaccharide biosynthesis often found in harmful bacteria overgrowth and linked to metabolic endotoxemia 2) increased bacterial chemotaxis (an indication of increased bacterial activity;movement) previously observed in obese mice. 3) increased microbial energy harvest (e.g. increased carbohydrate metabolism and fatty acid biosynthesis) linked to obesity and glucose intolerance.

They summarized their findings in the animal model as follows:

"Collectively, these results demonstrate that saccharin directly modulates the composition and function of the microbiome and induces dysbiosis, accounting for the downstream glucose intolerance phenotype in the mammalian host."

Part 2: Artificial Sweeteners Drive Similar Adverse Changes in Humans

In order to confirm that artificial sweeteners also drive adverse changes in humans, the researchers enrolled 381 non-diabetic individuals (44% males and 56% females) in a clinical nutritional study. Their results were reported as follows:

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