Objective Data from clinical research suggest that certain probiotic bacterial strains have the potential to modulate colonic inflammation. Nonetheless, these data differ between studies due to the probiotic bacterial strains used and the poor knowledge of their mechanisms of action.
Design By mass-spectrometry, we identified and quantified free long chain fatty acids (LCFAs) in probiotics and assessed the effect of one of them in mouse colitis.
Results Among all the LCFAs quantified by mass spectrometry in Escherichia coli Nissle 1917 (EcN), a probiotic used for the treatment of multiple intestinal disorders, the concentration of 3-hydroxyoctadecaenoic acid (C18-3OH) was increased in EcN compared with other E. coli strains tested. Oral administration of C18-3OH decreased colitis induced by dextran sulfate sodium in mice. To determine whether other bacteria composing the microbiota are able to produce C18-3OH, we targeted the gut microbiota of mice with prebiotic fructooligosaccharides (FOS). The anti-inflammatory properties of FOS were associated with an increase in colonic C18-3OH concentration. Microbiota analyses revealed that the concentration of C18-3OH was correlated with an increase in the abundance in Allobaculum, Holdemanella and Parabacteroides. In culture, Holdemanella biformis produced high concentration of C18-3OH. Finally, using TR-FRET binding assay and gene expression analysis, we demonstrated that the C18-3OH is an agonist of peroxisome proliferator activated receptor gamma.
Conclusion The production of C18-3OH by bacteria could be one of the mechanisms implicated in the anti-inflammatory properties of probiotics. The production of LCFA-3OH by bacteria could be implicated in the microbiota/host interactions.
- enteric bacterial microflora
- experimental colitis
- PPAR gamma
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JP and CP are joint first authors.
Contributors JLFP and CP designed and conducted experiments, performed data acquisition, analysis and interpretation, and wrote the manuscript. PLF designed and conducted experiments, performed data acquisition, analysis and interpretation and drafting of the manuscript. VE, GP, SM, TP-B, MVH, FB and CB carried out experiments, performed data acquisition, analysis. SC and FVI conducted experiments and contributed with the drafting of the manuscript. JB-M and EO contributed to data analysis and interpretation and edition of the manuscript. GD participated in the manuscript writing. PDC designed experiments, performed interpretation of data, helped with manuscript drafting and supervised microbiota study. NC designed and conducted experiments, performed analysis and interpretation of data, wrote the manuscript and directed the project.
Funding NC is a recipient of the grant from ANR (ANR-18-CE14-0039-01). PDC is a senior research associate at FRS-FNRS (Fonds de la Recherche Scientifique) and recipient of grants from FNRS (WELBIO-CR-2019C-02R, 'The Excellence Of Science: EOS 30770923') and the Funds Baillet Latour (Grant for Medical Research 2015). CK is a recipient of the grant from ANR (ENDIABAC, ANR-18-CE14-0007-01).
Competing interests None declared.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Patient consent for publication Not required.
Ethics approval All procedures were performed in accordance with the Guide for the Care and Use of Laboratory Animals of the European Council and were approved by the Animal Care and Ethics Committee of US006/CREFE (CEEA-122; application number APAFIS #7762-CE2016112509278235V2).
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information.
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