Decaisnea insignis Seed Oil Inhibits Trimethylamine- N-oxide Formation and Remodels Intestinal Microbiota to Alleviate Liver Dysfunction in l-Carnitine Feeding Mice

J Agric Food Chem. 2019 Nov 27;67(47):13082-13092. doi: 10.1021/acs.jafc.9b05383. Epub 2019 Nov 18.

Abstract

Elevated circulating level of the intestinal microbiota-derived l-carnitine metabolite trimethylamine-N-oxide (TMAO) has recently been linked to many chronic diseases. The purpose of our study was to investigate the effects of omega-7-enriched Decaisnea insignis seed oil (DISO) on reducing TMAO formation to prevent the l-carnitine-induced hepatic damage in mice. Feeding of mice with 3% l-carnitine in drinking water clearly increased the serum and urinary levels of TMAO (p < 0.05 vs Normal), whereas the serum and urinary TMAO formation was sharply reduced by DISO administration (p < 0.05). Meanwhile, DISO resulted in strong inhibition against the elevation of hepatic injury marker (AST, ALT, and ALP) activities and dyslipidemia (TC, TG, LDL-C, and HDL-C), as well as liver inflammatory cytokine (IL-1, IL-6, TNF-α, and TNF-β) release in l-carnitine-fed mice (p < 0.05). As revealed by 16S rDNA gene sequencing, DISO significantly inhibited the l-carnitine-induced elevations in the abundance of Firmicutes, Proteobacteria, and Erysipelotrichaceae and the increases in the proportion of Lactobacillus and Akkermansia, revealing that DISO attenuated the l-carnitine-caused gut dysbiosis. These findings suggested that DISO could alleviate liver dysfunction in l-carnitine-fed mice, which might be due to the protection against TMAO formation by modulating the gut microbiota.

Keywords: Decaisnea insignis seed oil (DISO); gut microbiota; l-carnitine; liver dysfunction; trimethylamine-N-oxide (TMAO).

MeSH terms

  • Animals
  • Bacteria / classification
  • Bacteria / genetics
  • Bacteria / isolation & purification
  • Carnitine / adverse effects*
  • Gastrointestinal Microbiome / drug effects*
  • Humans
  • Interleukin-1 / genetics
  • Interleukin-1 / metabolism
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Liver / drug effects
  • Liver / metabolism
  • Liver Diseases / drug therapy*
  • Liver Diseases / metabolism
  • Liver Diseases / microbiology
  • Magnoliopsida / chemistry*
  • Male
  • Methylamines / adverse effects
  • Mice
  • Plant Oils / pharmacology*
  • Seeds / chemistry

Substances

  • Interleukin-1
  • Interleukin-6
  • Methylamines
  • Plant Oils
  • trimethylamine
  • Carnitine