Gut Bacterial Metabolites from Tryptophan and Phenylalanine Induce Melatonin Synthesis and Extend Sleep Duration in Mice
  • Lee, Ji-Hyeok
  • Hwang, Su Jung
  • Ham, Song Lim
  • Kim, Jonghwan
  • Bang, Hye Jung
  • ... Kim, Gon Sup
  • 외 8명
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초록

The human gut microbiota significantly influences various physiological systems, including immune, nervous, and metabolic systems. Recent studies suggest that gut microbiota may affect sleep quality with certain bacteria and metabolites being linked to sleep patterns. However, the underlying chemical signaling pathway remains unclear. In this study, we investigated the effect of four gut bacteria-derived metabolites, tryptamine (1), indolokine A5 (2), 2-(1 ' H-indole-3 '-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE, 3), and phenethylamine (PEA, 4), on sleep characteristics in mice and melatonin biosynthesis pathways in zebrafish. Their sleep-promoting effects were evaluated in a pentobarbital-induced sleep mouse model, revealing significant increases in sleep duration and blood melatonin levels, particularly with ITE (3) and PEA (4). Further tests in zebrafish embryos showed that ITE (3) and PEA (4) increased the expression of genes for melatonin biosynthesis (Aanat1, Aanat2, Tph1a, and Hiomt) in a concentration-dependent manner, indicating their potential as therapeutic agents for sleep disorders.

키워드

ARYL-HYDROCARBON RECEPTORCIRCADIAN MELATONINMICROBIOTATEMPERATUREAMINESHEALTHRHYTHMYOUNG
제목
Gut Bacterial Metabolites from Tryptophan and Phenylalanine Induce Melatonin Synthesis and Extend Sleep Duration in Mice
저자
Lee, Ji-HyeokHwang, Su JungHam, Song LimKim, JonghwanBang, Hye JungPark, Joon-SukJang, Hyun-HeeKim, Tae YangPark, Jeong WooSeo, Young RokKim, Byeong SooKim, Gon SupLee, Hyo-JongKim, Chung Sub
DOI
10.1021/acsomega.4c06923
발행일
2024-10
유형
Article
저널명
ACS Omega
9
43
페이지
43875 ~ 43883