Gut microbiota regulates host melatonin production through epithelial cell MyD88

ABSTRACT

Melatonin has various physiological effects, such as the maintenance of circadian rhythms, anti-inflammatory functions, and regulation of intestinal barriers. The regulatory functions of melatonin in gut microbiota remodeling have also been well clarified; however, the role of gut microbiota in regulating host melatonin production remains poorly understood. To address this, we studied the contribution of gut microbiota to host melatonin production using gut microbiota-perturbed models. We demonstrated that antibiotic-treated and germ-free mice possessed diminished melatonin levels in the serum and elevated melatonin levels in the colon. The influence of the intestinal microbiota on host melatonin production was further confirmed by fecal microbiota transplantation. Notably, Lactobacillus reuteri (L. R) and Escherichia coli (E. coli) recapitulated the effects of gut microbiota on host melatonin production. Mechanistically, L. R and E. coli activated the TLR2/4/MyD88/NF-κB signaling pathway to promote expression of arylalkylamine N-acetyltransferase (AANAT, a rate-limiting enzyme for melatonin production), and MyD88 deficiency in colonic epithelial cells abolished the influence of intestinal microbiota on colonic melatonin production. Collectively, we revealed a specific underlying mechanism of gut microbiota to modulate host melatonin production, which might provide novel therapeutic ideas for melatonin-related diseases.

KEYWORDS:

• Melatonin
• lactobacillus reuteri
• Escherichia coli
• MyD88
• AANAT

Acknowledgments

We thank Prof. Bie Tan (Hunan Agricultural University, Changsha, China) for kindly support of Myd88^flox/flox Villin-Cre mice.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Authors’ contributions

W.K.R. supervised the entire project and designed the experiments. B.N.L. and L.J.F. performed the experiments and analyzed the data. Y.X.W., H.W., Y.Q.Y., S.C., I.F.H., C.X.L., H.W., and L.P.G. assisted with experiments. B.N.L. wrote the paper. W.K.R. revised the manuscript. All the authors have read and approved the final version of the manuscript.

Data availability statement

The raw 16S rDNA sequencing data generated in this study have been deposited in the NCBI Sequence Read Archive (https://www.ncbi.nlm.nih.gov/sra) under the accession number PRJNA1047195.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/19490976.2024.2313769

Additional information

Funding

This work was supported by the National Key Research and Development Program of China (2021YFD1300700), National Natural Science Foundation of China (U22A20510, 32225047, 32072687), National Center of Technology Innovation for Pigs (NCTIP-XD/B13), and the Double First-Class Discipline Promotion Project (2023B10564001).