Human intestinal bitter taste receptors regulate innate immune responses and metabolic regulators in obesity

An expression profiling was conducted to analyse the effect of the bitter tasting compounds denatonium benzoate (DB) or aloin on the transcriptome of human jejunal crypts compared to DMEM-treated crypts. These two bitter compounds are agonists for the human bitter taste receptor TAS2R43. We took advantage of a deletion polymorphism for TAS2R43, that exists in about 33% of the population to compare the effects of the TAS2R43 agonists in obese subjects that express (TAS2R43(+)) or do not express (TAS2R43(-)) TAS2R43. Primary jejunal crypts from lean (multi-organ donors) or obese (RYGB surgery) subjects were cultured for 24 hours and treated for 4 hours with either DMEM (control) or 1 mM DB or 30 µM aloin. In total 48 mRNA samples were subjected to RNAseq analysis. Overall design: 6 groups of human jejunal crypts of obese subjects: 1) TAS2R43+, DMEM treatment (n=8), 2) TAS2R43+, 1 mM denatonium benzoate (DB) (n=7), 3) TAS2R43+, 30µM aloin (n=6), 4) TAS2R43-, DMEM treatment (n=5), 5) TAS2R43-, 1 mM DB (n=6), 6) TAS2R43-, 30 µM aloin (n=4) 3 groups of human jejunal crypts of lean subjects with a TAS2R43+ genotype: 1) DMEM treatment (n=4), 1 mM DB (n=4), 5) 30 µM aloin (n=4)