<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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2025-02-01
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| author | Bodo Speckmann Paul M. Jordan Oliver Werz Robert K. Hofstetter Ellen Ehring Marie-Luise Vogel Koen Venema |
| author_facet | Bodo Speckmann Paul M. Jordan Oliver Werz Robert K. Hofstetter Ellen Ehring Marie-Luise Vogel Koen Venema |
| author_sort | Bodo Speckmann |
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| description | 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. |
| format | Article |
| id | doaj-art-705c0c87460c403480c0dba65eaf89cc |
| institution | OA Journals |
| issn | 2218-1989 |
| language | English |
| publishDate | 2025-02-01 |
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| series | Metabolites |
| spelling | doaj-art-705c0c87460c403480c0dba65eaf89cc2025-08-20T02:03:25ZengMDPI AGMetabolites2218-19892025-02-0115210510.3390/metabo15020105<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 IntestineBodo Speckmann0Paul M. Jordan1Oliver Werz2Robert K. Hofstetter3Ellen Ehring4Marie-Luise Vogel5Koen Venema6Evonik Operations GmbH, Rodenbacher Chaussee 4, 63457 Hanau, GermanyDepartment of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich Schiller University Jena, 07743 Jena, GermanyDepartment of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich Schiller University Jena, 07743 Jena, GermanyDepartment of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich Schiller University Jena, 07743 Jena, GermanyEvonik Operations GmbH, Rodenbacher Chaussee 4, 63457 Hanau, GermanyEvonik Operations GmbH, Rodenbacher Chaussee 4, 63457 Hanau, GermanyCentre for Healthy Eating & Food Innovation, Campus Venlo, Maastricht University, Villafloraweg 1, 5928 SZ Venlo, The NetherlandsBackground: 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.https://www.mdpi.com/2218-1989/15/2/105omega-3probioticmetabioticsynbioticinflammation resolutionnutritional therapy |
| spellingShingle | Bodo Speckmann Paul M. Jordan Oliver Werz Robert K. Hofstetter Ellen Ehring Marie-Luise Vogel Koen Venema <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 Metabolites omega-3 probiotic metabiotic synbiotic inflammation resolution nutritional therapy |
| title | <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 |
| title_full | <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 |
| title_fullStr | <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 |
| title_full_unstemmed | <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 |
| title_short | <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 |
| title_sort | 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 |
| topic | omega-3 probiotic metabiotic synbiotic inflammation resolution nutritional therapy |
| url | https://www.mdpi.com/2218-1989/15/2/105 |
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