Intense Sweeteners, Taste Receptors and the Gut Microbiome: A Metabolic Health Perspective

Abstract

Intense sweeteners (IS) are often marketed as a healthier alternative to sugars, with the potential to aid in combating the worldwide rise of diabetes and obesity. However, their use has been counterintuitively associated with impaired glucose homeostasis, weight gain and altered gut microbiota. The nature of these associations, and the mechanisms responsible, are yet to be fully elucidated. Differences in their interaction with taste receptors may be a potential explanatory factor. Like sugars, IS stimulate sweet taste receptors, but due to their diverse structures, some are also able to stimulate bitter taste receptors. These receptors are expressed in the oral cavity and extra-orally, including throughout the gastrointestinal tract. They are involved in the modulation of appetite, glucose homeostasis and gut motility. Therefore, taste genotypes resulting in functional receptor changes and altered receptor expression levels may be associated with metabolic conditions. IS and taste receptors may both interact with the gastrointestinal microbiome, and their interactions may potentially explain the relationship between IS use, obesity and metabolic outcomes. While these elements are often studied in isolation, the potential interactions remain unexplored. Here, the current evidence of the relationship between IS use, obesity and metabolic outcomes is presented, and the potential roles for interactions with taste receptors and the gastrointestinal microbiota in modulating these relationships are explored.

Do Gut Microbes Taste?

“…Turner et al [ 101 ] recently highlighted the gut microbiota’s likely involvement in altered nutrient sensing ability following regular consumption of artificial or intense sweetener (IS). Artificial sweeteners have been shown to have direct bacteriostatic effects on common gut microflora ( E. coli ) leading to dysbiosis (increased Firmicutes) [ 102 ].…”

“…Artificial sweeteners have been shown to have direct bacteriostatic effects on common gut microflora ( E. coli ) leading to dysbiosis (increased Firmicutes) [ 102 ]. Furthermore, receptor expression levels may change in response to this alteration in bacterial composition, resulting in altered metabolic functions like insulin resistance and obesity [ 101 , 103 , 104 ]. The gut microbiome’s role in these IS-consuming metabolic conditions is further supported by studies with fecal microbial transplant.…”

Diet Sugar-Free Carbonated Soda Beverage, Non-Caloric Flavors Consumption, and Diabetic Retinopathy: Any Linkage

“… 24 Activating the bitter receptors might increase the appetite and food consumption increasing weight. 25 On the other hand, authorities including FDA consider NNS safe if limited to acceptable daily intake (ADI), of note is that NNS is not uniform as aspartame and its degradation products are not contacting the microbiota. However, Potassium Acesulfame is absorbed and excreted in the urine and surprisingly it induced Firmicutes/ A. muciniphila disruption despite no direct contact.…”

Expression of Jejunal Taste Receptors in Women with Morbid Obesity

“…The activation of these GI receptors results in the release of intestinal hormones such as cholecystokinin (CKK) or glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 (GLP-1), which modulate the physiological response to nutrients, particularly satiety and the maintenance of energy homeostasis [ 21 ]. Recent studies carried out in humans and animal models with obesity and/or T2DM have demonstrated a downregulation of TASs, although the mechanisms are still unknown [ 22 , 23 ].…”