Human Gut Microbes Produce EPA- and DHA-Derived Oxylipins, but not N-Acyl-Ethanolamines, From Fish Oil

Area of Science:

• Microbiome research
• Human gut microbiota
• Nutritional biochemistry

Background:

• Human fecal microbiota can metabolize dietary polyunsaturated fatty acids (PUFAs).
• Previous work showed conversion of stearidonic acid to N-stearidonoyl-ethanolamine.
• The gut microbiome's role in metabolizing fish oil PUFAs into bioactive lipids is not fully understood.

Purpose of the Study:

• To investigate the metabolism of fish oil (FO)-derived docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) by human fecal microbiota.
• To determine if these metabolites include anti-inflammatory N-acyl-ethanolamines and oxylipins.
• To compare seasonal variations (summer vs. winter) in microbial processing of FO within a simulated intestinal environment.

Main Methods:

• Utilized a Simulator of the Human Intestinal Microbial Ecosystem (SHIME) with human fecal microbiota from different seasons.
• Administered fish oil (rich in DHA and EPA) to the SHIME model simulating different intestinal sections.
• Analyzed effluents using liquid chromatography-tandem mass spectrometry (LC-MS/MS) for PUFA metabolites, bacterial composition, and short-chain fatty acids (SCFAs).

Main Results:

• Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) levels increased over time, particularly with summer microbiota.
• Specific oxylipins, 17-hydroxy-docosahexaenoic acid and 15/18-hydroxy-eicosapentaenoic acid, were detected from DHA and EPA, respectively.
• No N-docosahexaenoyl-ethanolamine or N-eicosapentaenoyl-ethanolamine, or other N-acyl-ethanolamines, were found in any intestinal section or season.

Conclusions:

• Human fecal microbiota in the SHIME system can convert DHA and EPA from fish oil triglycerides into bioactive oxylipins.
• The formation of endocannabinoid-like N-acyl-ethanolamines from these specific omega-3 fatty acids was not observed.
• These findings highlight the microbiome's capacity to generate host-active oxylipins from dietary omega-3 fatty acids, but not necessarily N-acyl-ethanolamines.