(PTFS08-07-23) Metabolism of Dietary Polyunsaturated Fatty Acids by Gut Microbes

Objectives: A role for the gut microbiota in transforming dietary polyunsaturated fatty acids (PUFAs) into bioactive molecules is emerging. Microbiota-derived PUFA metabolites have the potential to engage host cell signaling pathways that affect intestinal health. However, identifying gut microbes that interact with dietary PUFAs and the metabolites produced from these interactions has largely been elusive and technically challenging. Few pathways of gut microbial PUFA metabolism are described in past studies, with especially little information on gut microbial metabolism of anti-inflammatory omega-3 PUFAs. We aim to identify gut bacterial species capable of taking up dietary omega-3 and omega-6 PUFAs, along with the bioactive bacterial metabolites produced from these PUFAs. Our findings will elucidate the role of gut bacteria in processing dietary PUFAs, suggesting whether gut bacteria may mediate effects of PUFAs on host intestinal health.

Methods: We employ a workflow developed by our lab, called Bioorthogonal Labeling-Sort-Sequence-Spectrometry (BOSSS), to define interactions between PUFAs and gut microbes. Gut-associated bacteria in mice and in bacterial cultures are treated with chemically modified PUFAs that can be fluorescently labeled, so cells that exhibit fluorescence following PUFA treatment are likely capable of PUFA uptake. Modified PUFAs and their metabolic derivatives are analyzed by mass spectrometry to characterize microbial PUFA-derived metabolites. The effects of these microbial metabolites on mammalian intestinal cells are assessed using transcriptomics.

Results: Multiple gut microbes exhibited fluorescence staining that indicated these species take up the omega-3 PUFA eicosapentaenoic acid (EPA) and the omega-6 PUFA linoleic acid (LA). A collection of novel PUFA-interacting taxa was identified. Bacterial EPA-derived metabolites were characterized and altered gene expression in the human intestinal Caco-2 cell line.

Conclusions: Novel interactions between dietary PUFAs and select gut-associated bacterial species were identified using the BOSSS workflow. In particular, the gut microbiota can convert EPA to bioactive metabolites that have a potential to modulate host intestinal biology.

Funding Sources: This research is funded by NIH NIGMS and NIH NIDDK.