Intestinal dual-specificity phosphatase 6 regulates the cold-induced gut microbiota remodeling to promote white adipose browning

Pei Chen Chen, Tzu Pei Tsai, Yi Chu Liao, Yu Chieh Liao, Hung Wei Cheng, Yi Hsiu Weng, Chiao Mei Lin, Cheng Yuan Kao, Chih Cheng Tai, Jhen Wei Ruan

Research output: Contribution to journalArticlepeer-review

Abstract

Gut microbiota rearrangement induced by cold temperature is crucial for browning in murine white adipose tissue. This study provides evidence that DUSP6, a host factor, plays a critical role in regulating cold-induced gut microbiota rearrangement. When exposed to cold, the downregulation of intestinal DUSP6 increased the capacity of gut microbiota to produce ursodeoxycholic acid (UDCA). The DUSP6-UDCA axis is essential for driving Lachnospiraceae expansion in the cold microbiota. In mice experiencing cold-room temperature (CR) transitions, prolonged DUSP6 inhibition via the DUSP6 inhibitor (E/Z)-BCI maintained increased cecal UDCA levels and cold-like microbiota networks. By analyzing DUSP6-regulated microbiota dynamics in cold-exposed mice, we identified Marvinbryantia as a genus whose abundance increased in response to cold exposure. When inoculated with human-origin Marvinbryantia formatexigens, germ-free recipient mice exhibited significantly enhanced browning phenotypes in white adipose tissue. Moreover, M. formatexigens secreted the methylated amino acid Nε-methyl-L-lysine, an enriched cecal metabolite in Dusp6 knockout mice that reduces adiposity and ameliorates nonalcoholic steatohepatitis in mice. Our work revealed that host-microbiota coadaptation to cold environments is essential for regulating the browning-promoting gut microbiome.

Original languageEnglish
Article number22
Journalnpj Biofilms and Microbiomes
Volume10
Issue number1
DOIs
Publication statusPublished - 2024 Dec

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Microbiology
  • Applied Microbiology and Biotechnology

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