Low-Dose Stevia (Rebaudioside A) Consumption Perturbs Gut Microbiota and the Mesolimbic Dopamine Reward System

Abstract

Stevia is a natural low-calorie sweetener that is growing in popularity in food and beverage products. Despite its widespread use, little is understood of its impact on the gut microbiota, an important environmental factor that can mediate metabolism and subsequent obesity and disease risk. Furthermore, given previous reports of dysbiosis with some artificial low-calorie sweeteners, we wanted to understand whether prebiotic consumption could rescue potential stevia-mediated changes in gut microbiota. Three-week old male Sprague–Dawley rats were randomized to consume: (1) Water (CTR); (2) Rebaudioside A (STV); (3) prebiotic (PRE); (4) Rebaudioside A + prebiotic (SP) (n = 8/group) for 9 weeks. Rebaudioside was added to drinking water and prebiotic oligofructose-enriched inulin added to control diet (10%). Body weight and feces were collected weekly and food and fluid intake biweekly. Oral glucose and insulin tolerance tests, gut permeability tests, dual X-ray absorptiometry, and tissue harvest were performed at age 12 weeks. Rebaudioside A consumption alone did not alter weight gain or glucose tolerance compared to CTR. Rebaudioside A did, however, alter gut microbiota composition and reduce nucleus accumbens tyrosine hydroxylase and dopamine transporter mRNA levels compared to CTR. Prebiotic animals, alone or with Rebaudioside A, had reduced fat mass, food intake, and gut permeability and cecal SCFA concentration. Adding Rebaudioside A did not interfere with the benefits of the prebiotic except for a significant reduction in cecal weight. Long-term low-dose Rebaudioside A consumption had little effect on glucose metabolism and weight gain; however, its impact on gut microbial taxa should be further examined in populations exhibiting dysbiosis such as obesity.

Plausible Biological Interactions of Low- and Non-Calorie Sweeteners with the Intestinal Microbiota: An Update of Recent Studies

“…However, only stevia rebaudioside A increased SCFAs acetate and valerate, which are positively correlated with fat mass and total weight. Hence, stevia rebaudioside A seems to decrease the "healthy" status of the gut microbiota [55].…”

Human Milk Oligosaccharide Supplementation Affects Intestinal Barrier Function and Microbial Composition in the Gastrointestinal Tract of Young Sprague Dawley Rats

“…Fecal matter was collected at three, seven, and 11 weeks of age, snap-frozen, and stored at −80 • C. Microbial profiling was performed based on our previous work [22][23][24]. Briefly, bacterial DNA was extracted from~60 mg of stool using the FastDNA spin kit for feces (MP Biomedicals, Lachine, QC, Canada).…”

“…Half of the extracted sample was brought to a concentration of 4 ng/µL prior to storage at −20 • C for qPCR analysis, and the other half was used for 16S ribosomal RNA (rRNA) sequencing at the Center for Health Genomics and Informatics at the University of Calgary. Quantitative PCR (qPCR) was carried out as previously described [22][23][24] with primers that covered the major gut bacterial groups in rodents (Table S2, Supplementary Materials).…”

Low Calorie Sweeteners Differ in Their Physiological Effects in Humans

“…Studies have reported that mice consuming 0.1 mg mL −1 of pure saccharin (equivalent to 5 mg/kg BW) [137] and 2–3 mg/kg BW stevia [138] induce dysbiosis in the gut microbiota, with mixed evidence for 1.1–15 mg/kg BW per day of sucralose [136,139]. Furthermore, the dysbiosis in the gut was associated with glucose intolerance in mice consuming 0.1 mg mL −1 of pure saccharin on a HFD [137], while the change in the gut microbiotadid not affect BW, food intake or insulin sensitivity in rats consuming 2–3 mg/kg BW of stevia [138]. However, food and water intake was only measured in a subset of mice consuming 0.1 mg mL −1 of pure saccharin, and may not be representative of the entire population [131,137].…”