Sweeteners lead to obesity by acting on the intestinal microflora
About the principles of sugar substitutes, experiments with laboratory mice and human microbiota
On October 9, the journal Nature published the results of a study demonstrating that eating sugar substitutes leads to physiological changes typical of obesity, and microorganisms living in us are responsible for such changes (Suez et al., Artificial sweeteners induce glucose intolerance by altering the gut microbiota). We asked the microbiologist, Doctor of Biological Sciences Konstantin Severinov to comment on this discovery.
Overweight is considered a universal negative consequence of the modern lifestyle and is associated with a number of serious diseases, in particular diabetes, one of the precursors of which is high blood sugar. Limiting the amount of sugar in food is a common way to lose weight, and is also absolutely necessary for diabetics. At the same time, low–calorie sugar substitutes - saccharin or aspartame - are widely used to preserve the taste of food. These substances are considered harmless and are the most common food additives in the world (think, for example, diet Coke). Unlike sugar, sweeteners are not a source of energy, and, therefore, their use should not lead to the accumulation of excess weight. In addition, it is believed that they do not contribute to an increase in blood sugar levels, which is usually observed after eating and which is unacceptable for diabetics. However, the use of sweeteners often does not lead to weight loss, which, as a rule, is the root cause of their use.
In the October 9, 2014 issue of the journal Nature, a large article by Israeli authors was published, which shows that eating food containing sweeteners leads to physiological changes that are typical for obesity, that is, to the opposite effect to that sought by consumers of sweeteners. In addition, the authors show in direct experiments that the microbes inhabiting us are responsible for this unexpected (and undesirable) effect.
The study examined mice whose drinking water was supplemented with one of three common sweeteners in concentrations typical of commercial products containing these substances. Control groups of animals received water without additives or water with glucose or sucrose (that is, ordinary dietary sugar). After 11 weeks, all mice treated with sugar substitutes developed glucose tolerance (reduced glucose tolerance – VM) – a prediabetic condition characterized by an increased blood sugar content.
Graph from the popular retelling of the article on the Darwins Dreams website – VM
Studies conducted on different lines of mice and under different diets have led to the conclusion that the occurrence of hyperglycemia as a result of the use of sweeteners is a common property and is observed both in overweight animals and in normal animals.
Since the sweeteners themselves are not digested by the body, it was assumed that they affect the intestinal microbiota – a diverse and extremely numerous microbes inhabiting the intestines of mammals. Indeed, it turned out that the spectrum of microbes in animals that received sweeteners significantly and significantly differed from the control. Moreover, it turned out that the addition of a sweetener to the community of intestinal microbes growing in the laboratory on Petri dishes, that is, outside the mouse, also led to similar changes.
However, by themselves, these observations do not establish a link between induced hyperglycemia and changes in the microbiota. Two experiments were made to establish such a connection. Firstly, hyperglycemic mice treated with sweeteners were treated with broad-spectrum antibiotics (while the sweetener was continued to be added to their water). After a course of antibiotic therapy, hyperglycemia disappeared, which indicates that this condition is really somehow related to the microbiota. In another experiment, fecal transplants were performed from hyperglycemic mice treated with a sugar substitute to sterile mice that did not have their own microbiota. It turned out that fecal transplantation from hyperglycemic, but not from control animals, led to the rapid development of hyperglycemia in recipient mice. Thus, it is proved that hyperglycemia is "intertwined" together with intestinal microbes contained in feces, and therefore, it is these microbes, whose composition changes when using sweeteners, that are responsible for the prediabetic state.
These observations are not limited to mice: experiments on volunteers have shown that the use of sugar substitutes leads to symptoms of glucose tolerance and changes in the microbiota in humans, and fecal transplantation from such people to sterile mice is guaranteed to lead to hyperglycemia in them.
The published results convincingly show that sweeteners should be used with caution, and once again demonstrate the role of the microbiota in the norm and in the development of diseases. As for the mechanism by which the modified community of intestinal microbes increases the amount of sugar in the blood, there is no answer to this fundamental question. An increase in the proportion of bacteria capable of extracting nutrients more actively from low-calorie foods can be considered as a hypothesis. On the other hand, it is possible that dysbiosis caused by the use of sugar substitutes leads – directly or indirectly – to the suppression of certain intestinal microbes, which are not yet known to science, which secrete special substances that limit the accumulation of sugar in the blood. The choice between these two possibilities will ultimately determine the strategy for controlling the undesirable consequences of using sweeteners.
Konstantin Severinov – Doctor of Biological Sciences, Head of the Laboratory of Regulation of Gene Expression of Prokaryotic Elements of the Institute of Molecular Genetics of the Russian Academy of Sciences, Head of the Laboratory of Molecular Genetics of Microorganisms of the Institute of Gene Biology of the Russian Academy of Sciences, Professor at Rutgers University (USA), Professor at the Skolkovo Institute.
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14.10.2014