Melatonin relieves hepatic lipid dysmetabolism caused by aging via modifying the secondary bile acid pattern of gut microbes

It has been reported that aging-generated gut microecosystem may promote host hepatic lipid dysmetabolism through shaping the pattern of secondary bile acids (BAs). Then as an oral drug, melatonin (Mel)-mediated beneficial efforts on the communication between gut microbiota and aging host are still not clearly. Here, we show that aging significantly shapes the pattern of gut microbiota and BAs, whereas Mel treatment reverses these phenotypes (P < 0.05), which is identified to depend on the existence of gut microbiota. Mechanistically, aging-triggered high-level expression of ileac farnesoid X receptor (FXR) is significantly decreased through Mel-mediated inhibition on Campylobacter jejuni (C. jejuni)-induced deconjugation of tauroursodeoxycholic acid (TUDCA) and glycoursodeoxycholic acid (GUDCA) (P < 0.05). The aging-induced high-level of serum taurine chenodeoxycholic acid (TCDCA) activate trimethylamine-N-oxide (TMAO)-triggered activating transcriptional factor 4 (ATF4) signaling via hepatic FXR, which further regulates hepatic BAs metabolism, whereas TUDCA inhibits aging-triggered high-level of hepatic ATF4. Overall, Mel reduces C. jejuni-mediated deconjugation of TUDCA to inhibit aging-triggered high-level expression of hepatic FXR, which further decreases hepatic TMAO production, to relieve hepatic lipid dysmetabolism.

Automated summary

It has been reported that aging-induced changes in the gut microbiota may promote hepatic lipid dysmetabolism by shaping the pattern of secondary bile acids. Melatonin treatment reverses these effects and inhibits the expression of hepatic FXR, leading to a decrease in hepatic TMAO production and relief of hepatic lipid dysmetabolism.