However, their team also observed poor expression of hT2R9 receptors on the surface of their cells, and none of 104 compounds in their test battery activated hT2R9. No, Is the Subject Area "Inflammation" applicable to this article? . In this study, the components of the gut microbiome were altered in Ace-K-treated mice (Fig 1B and 1C). 2005) was used to examine the extent of LD between each pair of markers and to determine haplotype block structure. 2010). Drayna Larsen DNA was isolated from frozen fecal pellets collected at different time points using a PowerSoil DNA Isolation Kit (Mo Bio Laboratories) according to the manufacturer’s instruction, and the resultant DNA was quantified and stored at -80°C for further analysis. For example, in Ace-K-treated female mice, LPS synthesis-related genes, including UDP-glucose:(heptosyl) LPS alpha-1,3-glucosyltransferase, ADP-L-glycero-D-manno-heptose 6-epimerase, amino-4-deoxy-L-arabinose transferase, UDP-D-GlcNAcA oxidase and UDP-GlcNAc3NAcA epimerase, were significantly increased. Acesulfame potassium and saccharin are well-studied nonnutritive sweeteners commonly found in food products. This study provides novel insights into the effects of artificial sweetener consumption on host health and highlights the role of the gut microbiome and bacterial products in regulating host metabolic homeostasis. Ace-K consumption led to a significant increase in body weight in male mice, potentially by disrupting the gut bacterial compositions and activating bacterial energy harvesting pathways. Recently, this finding was confirmed for the TAS2R38 genotype and A. bunius berries, although the specific ligand itself was not isolated (Reed D, personal communication). Supplementary material can be found at Supplementary Data. CC AN Jorde Dotson Finally, participants completed a standard propylthiouracil (PROP) phenotyping protocol with PROP, salt, and tones. L Clark Because the effects of these 2 SNPs did not appear to deviate from additivity, a score of 1 was assigned for each putatively functional allele for each of the SNPs, resulting in 2 variables coded 0, 1, and 2. 2005; Duffy et al. Total time in the laboratory for session 1 was ~1 h; all data were collected one-on-one by project staff. M Snyder Mice were euthanized with CO2 in an appropriate chamber by trained personnel. 2010). Therefore, the examination of gender-specific gut microbiome responses to Ace-K consumption would be highly informative. Alleva Department of Environmental Health Science, University of Georgia, Athens, Georgia, United States of America, Affiliation JR P 2012). Delwiche 2007; Roudnitzky et al. The relative abundances of numerous genes involved in carbohydrate absorption or transport, including glucose uptake protein, lactose permease, monosaccharide-transporting ATPase, components of multiple sugar and D-allose transport systems, and different types of phosphotransferase systems, were significantly reduced. Genotypes were assigned automatically via MassARRAY software (Sequenom) and independently inspected by 2 technicians. Acesulfame-K (Ace-K) is one of the major low-calorie artificial sweeteners in the modern diet. All primers were purchased from Integrated DNA Technologies. VB LM Previously, it has been hypothesized that mutations in TAS2Rs may drive a gain of function for an alternative ligand (e.g., Wooding et al. Reilly Zuker 2005). . 2008). Wallace Prior evidence (Roudnitzky et al. Tang Lewtschenko . Hayes SD In particular, the interaction between the host and gut microbiome is complicated, and many host characteristics can influence the responses of the gut microbiome to external stimuli. This model explained 13.4% of the variance in bitterness (P < 0.001), and the recoded variables for Val187Ala (P = 0.021) in TAS2R9 and Val240Ile (P = 0.008) in TAS2R31 were both significant. The cloud and PLS-DA plots shown in Fig 5 reveal that the gut microbial metabolomes of the Ace-K-administered animals were different from those of the controls, regardless of gender. JK S Further validation in a larger number of animals or a human cohort is needed. Participants were oriented to the psychophysical scale, and sampled 6 perceptually complex tastants and irritants, rating them for multiple qualities. LM. Bartoshuk We found no evidence that the Ala227Val SNP was associated with AceK sweetness [F(2,98) = 0.15; P = 0.86] or the perceived bitterness ratings of PROP [F(2,98) = 1.27; P = 0.29]. However, we find this interpretation unsatisfying, as we would also expect untrained participants to dump any aversive, unpleasant sensations into the bitter response option (Clark and Lawless 1994). AC Conversely, for AceK bitterness, the perceived intensity varies not only as a function of overall taste response but also as a function of variation in TAS2R31 and possibly other TAS2R genes. 2011) and in vivo (Pronin et al. 2000; Chandrashekar et al. Hofmann Hayes Some epidemiological studies have shown that artificial sweeteners are beneficial for weight loss and to those who suffer from glucose intolerance and type 2 diabetes mellitus [1]. Risch Wooding Davidson BT 2006-10-26. DNA was collected from saliva using Oragene collection kits according to manufacturer instructions (Genotek Inc.). Kuhn S 2012). These data are largely consistent with earlier psychophysical data showing that the bitterness of AceK and saccharin covaries with each other but not with propylthiouracil (Horne et al. Feng This suggests that the putatively functional SNPs identified here make an independent contribution to the bitterness of AceK. As shown in Figure 3, the Val240 homozygotes (n = 35) reported less bitterness from AceK than the Ile240 homozygotes (n = 20) (Tukey–Kramer P = 0.010). However, the changes in specific metabolites were largely different in male and female mice, with the majority of metabolites being down-regulated and up-regulated in female and male mice, respectively, which was consistent with the differential changes in the gut bacterial community composition and functional genes in the female and male animals. DJ In the future, whole gene sequencing of TAS2Rs may be required to better explain phenotypic variation. In particular, it seems possible that rare TAS2R31 variants may reduce response in vivo. Previously, we reported that the bitterness of grapefruit juice varies as a function of a polymorphism in TAS2R19 (Hayes et al. Mueller As outlined above, numerous studies have demonstrated that the perception of bitter taste in humans is moderated by genetic variation in TAS2R genes (Duffy, Davidson, et al. Dinehart CD A pilot study and prior experience were used to determine appropriate concentrations. J BP LM. MG LB The 1-kHz tones were generated with a Maico MA39 audiometer calibrated to deliver the specified sound pressure level binaurally; stimuli ranged from 50 to 90 dB in 10 dB steps.