DSM 32963 Enhances Specialized Pro-Resolving Mediator Production from an -3 PUFA Salt in a Dynamic Model of the Human Intestine.

Background: Omega-3 polyunsaturated fatty acids (-3 PUFA) have been used in the treatment of inflammatory bowel diseases (IBD) and irritable bowel syndrome (IBS), and their effects are potentiated upon conversion to specialized pro-resolving mediators (SPM). Recent studies indicated that the probiotic bacterial strain DSM 32963 can be used to enhance the production of SPM and its precursors in vivo.

Methods: Here, we explored the contribution of DSM 32963 to SPM production in a validated, dynamic model of the upper and lower intestine. The TIM-1 and TIM-2 models were applied, with the TIM-2 model inoculated with the fecal microbiota of healthy individuals and probed with an -3 PUFA lysine salt with and without DSM 32963 or an SPM-enriched fish oil or placebo. Kinetics of SPM production were assessed by metabololipidomics analysis, and survival and engraftment of the strain was monitored by plate counting and by strain-specific qPCR.

Results: DSM 32963 poorly survived TIM-1 conditions but propagated in the TIM-2 model, where it enabled the metabolism of -3 PUFA to SPM (resolvin E2 and protectin DX) and SPM precursors (e.g., 5-hydroxyeicosapentaenoic acid (5-HEPE), 15-HEPE, 18-HEPE, 4-hydroxydocosahexaenoic acid (4-HDHA), 10-HDHA, and 17-HDHA, among other EPA- and DHA-derived metabolites) with significantly higher levels of lipid mediator production compared to the -3 PUFA lysine salt alone; esterified -3 PUFA were hardly converted by the microbiota.

Conclusions: These findings reinforce that DSM 32963 facilitates SPM production in situ from bioavailable -3 PUFA in the large intestine, highlighting its use to complement eukaryotic SPM biosynthesis by the host and its possible therapeutic use for, e.g., IBD and IBS.