Lipopolysaccharide increases bitter taste sensitivity via epigenetic changes in Tas2r gene clusters

Cailu Lin; Masafumi Jyotaki; John Quinlan; Shan Feng; Minliang Zhou; Peihua Jiang; Ichiro Matsumoto; Liquan Huang; Yuzo Ninomiya; Robert F Margolskee; Danielle R Reed; Hong Wang

doi:10.1016/j.isci.2023.106920

Lipopolysaccharide increases bitter taste sensitivity via epigenetic changes in Tas2r gene clusters

iScience. 2023 May 19;26(6):106920. doi: 10.1016/j.isci.2023.106920. eCollection 2023 Jun 16.

Authors

Cailu Lin¹, Masafumi Jyotaki¹, John Quinlan¹, Shan Feng¹, Minliang Zhou¹, Peihua Jiang¹, Ichiro Matsumoto¹, Liquan Huang^{1

2}, Yuzo Ninomiya^{1

3

4

5}, Robert F Margolskee¹, Danielle R Reed¹, Hong Wang¹

Affiliations

¹ Monell Chemical Senses Center, 3500 Market St., Philadelphia, PA 19104, USA.
² Institute of Cellular and Developmental Biology, College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, China.
³ Division of Sensory Physiology, Research and Development Center for Five-Sense Device, Kyushu University, Fukuoka, Japan.
⁴ Okayama University, Okayama, Japan.
⁵ Oral Science Research Center, Tokyo Dental College, Tokyo, Japan.

Abstract

T2R bitter receptors, encoded by Tas2r genes, are not only critical for bitter taste signal transduction but also important for defense against bacteria and parasites. However, little is known about whether and how Tas2r gene expression are regulated. Here, we show that in an inflammation model mimicking bacterial infection using lipopolysaccharide, the expression of many Tas2rs was significantly upregulated and mice displayed markedly increased neural and behavioral responses to bitter compounds. Using single-cell assays for transposase-accessible chromatin with sequencing (scATAC-seq), we found that the chromatin accessibility of Tas2rs was highly celltype specific and lipopolysaccharide increased the accessibility of many Tas2rs. scATAC-seq also revealed substantial chromatin remodeling in immune response genes in taste tissue stem cells, suggesting potential long-lasting effects. Together, our results suggest an epigenetic mechanism connecting inflammation, Tas2r gene regulation, and altered bitter taste, which may explain heightened bitter taste that can occur with infections and cancer treatments.

Keywords: Behavioral neuroscience; Epigenetics; Sensory neuroscience; Transcriptomics.

Abstract

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