Bitter taste receptors (Tas2rs in mice) detect bitterness, a warning signal for toxins and poisons, and are expressed in enteroendocrine cells. We tested the hypothesis that Tas2r138 and Tas2r116 mRNAs are modulated by microbiota alterations induced by a long-term high-fat diet (HFD) and antibiotics (ABX) (ampicillin and neomycin) administered in drinking water. Cecum and colon specimens and luminal contents were collected from C57BL/6 female and male mice for qRT-PCR and microbial luminal 16S sequencing. HFD with/without ABX significantly increased body weight and fat mass at 4, 6, and 8 weeks. Tas2r138 and Tas2r116 mRNAs were significantly increased in mice fed HFD for 8 weeks vs. normal diet, and this increase was prevented by ABX. There was a distinct microbiota separation in each experimental group and significant changes in the composition and diversity of microbiome in mice fed a HFD with/without ABX. Tas2r mRNA expression in HFD was associated with several genera, particularly with Akkermansia, a Gram-negative mucus-resident bacterium. These studies indicate that luminal bacterial composition is affected by sex, diet, and ABX and support a microbial dependent upregulation of Tas2rs in HFD-induced obesity, suggesting an adaptive host response to specific diet-induced dysbiosis.

Since 2005, SOX2 has raised the attention of the scientific community for being one of the key transcription factors responsible for pluripotency induction in somatic stem cells. Our research investigated the turnover regulation of SOX2 mRNA in human adipose-derived stem cells, considered one of the most valuable sources of somatic stem cells in regenerative medicine. Mitoxantrone, is a drug acting on nucleic acids primarily used to treat certain types of cancer, and recently re-addressed to ameliorate the outcome of autoimmune diseases such as multiple sclerosis. Additionally, mitoxantrone has been shown to inhibit the binding of Human antigen R (HuR) RNA binding protein to TNF alpha mRNA. Our results show that HuR binds to the 3'UTR region of SOX2 mRNA together with the RNA-induced silencing complex-miR145. The HuR binding works by stabilizing the interaction between the 3' UTR and RISC. Cell exposure to mitoxantrone leads to HuR detachment, and the subsequent prolongation of the SOX2 mRNA half-life. The prolonged SOX2 half-life allows to an improvement of the spheroid forming capability of the adipose-derived stem cells. The silencing of HuR confirmed the above observations, and illustrates how the RNA binding protein HuR may be a required molecule for regulation of SOX2 mRNA decay.