<i>Bacillus</i> <i>megaterium</i> DSM 32963 Enhances Specialized Pro-Resolving Mediator Production from an <i>n</i>-3 PUFA Salt in a Dynamic Model of the Human Intestine
Background: Omega-3 polyunsaturated fatty acids (<i>n</i>-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 indica...
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| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-02-01
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| Series: | Metabolites |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2218-1989/15/2/105 |
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| Summary: | Background: Omega-3 polyunsaturated fatty acids (<i>n</i>-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 <i>Bacillus megaterium</i> DSM 32963 can be used to enhance the production of SPM and its precursors in vivo. Methods: Here, we explored the contribution of <i>Bacillus megaterium</i> 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 <i>n</i>-3 PUFA lysine salt with and without <i>Bacillus megaterium</i> 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 <i>Bacillus megaterium</i> strain was monitored by plate counting and by strain-specific qPCR. Results: <i>Bacillus megaterium</i> DSM 32963 poorly survived TIM-1 conditions but propagated in the TIM-2 model, where it enabled the metabolism of <i>n</i>-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 <i>n</i>-3 PUFA lysine salt alone; esterified <i>n</i>-3 PUFA were hardly converted by the microbiota. Conclusions: These findings reinforce that <i>Bacillus megaterium</i> DSM 32963 facilitates SPM production in situ from bioavailable <i>n</i>-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. |
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| ISSN: | 2218-1989 |