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Microbiota-Dependent Upregulation of Bitter Taste Receptor Subtypes in the Mouse Large Intestine in High-Fat
Filippo Caremoli1,2, Jennifer Huynh1,2,3, Venu Lagishetty1,2
1Division of Digestive Diseases, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Abstract:
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.
Insights
A high-fat diet (HFD) alters gut bacteria, increasing bitter taste receptor (Tas2r) mRNA levels. Antibiotics prevent this Tas2r upregulation, suggesting a link between gut microbiota and host response in obesity.
Area of Science:
- Gastroenterology
- Microbiology
- Molecular Biology
Background:
- Bitter taste receptors (Tas2rs) are crucial for detecting toxins and are found in enteroendocrine cells.
- Gut microbiota plays a significant role in host physiology and metabolism.
Purpose of the Study:
- To investigate how high-fat diet (HFD) and antibiotic (ABX) treatments alter gut microbiota composition.
- To determine the effect of these alterations on the expression of bitter taste receptor (Tas2r) mRNAs (Tas2r138 and Tas2r116).
Main Methods:
- Mice were fed a HFD with or without ABX (ampicillin and neomycin) for 8 weeks.
- Body weight and fat mass were measured.
- Gene expression of Tas2r138 and Tas2r116 was analyzed using qRT-PCR in cecum and colon tissues.
- Gut microbiota composition was analyzed using 16S rRNA sequencing.
Main Results:
- HFD significantly increased body weight and fat mass, an effect mitigated by ABX.
- Tas2r138 and Tas2r116 mRNA levels were significantly elevated in mice on HFD for 8 weeks, and this increase was prevented by ABX.
- Both HFD and ABX treatments induced significant changes in gut microbiota composition and diversity.
- Tas2r mRNA expression in HFD was associated with specific bacterial genera, notably *Akkermansia*.
Conclusions:
- Gut microbiota composition is influenced by sex, diet, and antibiotic treatment.
- HFD-induced obesity is associated with a microbiota-dependent upregulation of Tas2rs.
- This suggests an adaptive host response to diet-induced gut dysbiosis.
