New quantitative structure–activity relationship (QSAR) models for bitter peptides were built with integrated amino acid descriptors. Datasets contained 48 dipeptides, 52 tripeptides and 23 tetrapeptides with their reported bitter taste thresholds. Independent variables consisted of 14 amino acid descriptor sets. A bootstrapping soft shrinkage approach was utilized for variable selection. The importance of a variable was evaluated by both variable selecting frequency and standardized regression coefficient. Results indicated model qualities for di-, tri- and tetrapeptides with R2 and Q2 at 0.950 ± 0.002, 0.941 ± 0.001; 0.770 ± 0.006, 0.742 ± 0.004; and 0.972 ± 0.002, 0.956 ± 0.002, respectively. The hydrophobic C-terminal amino acid was the key determinant for bitterness in dipeptides, followed by the contribution of bulky hydrophobic N-terminal amino acids. For tripeptides, hydrophobicity of C-terminal amino acids and the electronic properties of the amino acids at the second position were important. For tetrapeptides, bulky hydrophobic amino acids at N-terminus, hydrophobicity and partial specific volume of amino acids at the second position, and the electronic properties of amino acids of the remaining two positions were critical. In summary, this study not only constructs reliable models for predicting the bitterness in different groups of peptides, but also facilitates better understanding of their structure-bitterness relationships and provides insights for their future studies.

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The microbiome has been implicated in blood pressure regulation and recent studies have found that gut‐derived microbial short chain fatty acids (SCFAs) modulate blood pressure. This is mediated, at least in part, by Olfactory receptor 78 (Olfr78), a G‐protein coupled receptor (GPCR) which responds to SCFAs to modulate renin release. Other renal GPCRs which respond to SCFAs include Olfr558, Gpr41, and Gpr43. Although we have previously studied the physiology of Olfr78 null mice, we do not know whether the expression of the other SCFA receptors, or other key renal genes, are altered in these animals. To address this, we extracted RNA from murine kidneys (8 Olfr78 WTs and 5 Olfr78 KOs) and performed reverse transcription and quantitative PCR using Taqman probe sets for 2 SCFA ORs (Olfr78, Olfr558), 2 SCFA GPCRs (Gpr41, Gpr43), as well as genes of interest (Renin1, Avpr2, Aqp2, ENaC, ROMK, BKA, and Wnt5a), and Gapdh as a control. From our screen, three genes were significantly decreased (p<0.05) in Olfr78 null mice when compared to WT: Olfr558 (mean fold change ± s.d., WT 1 ± 0.49, KO 0.34 ± 0.26), Aqp2 (WT 1 ± 0.51, KO 0.25 ± 0.11), and ROMK (WT 1 ± 0.36, KO 0.52 ± 0.20). The other genes assayed did not change between genotypes. Although we are not properly powered to examine sex, we did include both males and females and did not note any sex differences. Notably, novel changes in Aqp2 and ROMK expression imply potential changes in water or potassium handling in these animals. Future studies will include RNAScope and immunohistochemistry confirmation of these findings, as well as functional studies to determine the consequences of these changes.