Bacteria-derived long chain fatty acid exhibits anti-inflammatory properties in colitis

Gut. 2021 Jun;70(6):1088-1097. doi: 10.1136/gutjnl-2020-321173. Epub 2020 Sep 25.

Abstract

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.

Keywords: PPAR gamma; enteric bacterial microflora; experimental colitis; lipids; probiotics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacteroidetes
  • Caco-2 Cells
  • Cell Membrane Permeability
  • Chemokine CXCL1 / genetics
  • Colitis / chemically induced
  • Colitis / drug therapy*
  • Colitis / metabolism
  • Dextran Sulfate
  • Epithelial Cells / physiology
  • Escherichia coli / metabolism
  • Firmicutes / metabolism
  • Gastrointestinal Microbiome / physiology
  • Gene Expression / drug effects
  • Humans
  • Interleukin-1beta / genetics
  • Intestinal Mucosa / metabolism*
  • Mass Spectrometry
  • Mice
  • Oligosaccharides / pharmacology
  • PPAR gamma / genetics
  • PPAR gamma / metabolism*
  • Pancreatitis-Associated Proteins / genetics
  • Permeability
  • Peyer's Patches
  • Prebiotics
  • Probiotics / chemistry
  • Stearates / analysis
  • Stearates / metabolism*
  • Stearates / therapeutic use*
  • Zonula Occludens-1 Protein / genetics

Substances

  • Chemokine CXCL1
  • Cxcl1 protein, mouse
  • IL1B protein, mouse
  • Interleukin-1beta
  • Oligosaccharides
  • PPAR gamma
  • Pancreatitis-Associated Proteins
  • Pparg protein, mouse
  • Prebiotics
  • Reg3g protein, mouse
  • Stearates
  • Tjp1 protein, mouse
  • Zonula Occludens-1 Protein
  • fructooligosaccharide
  • 3-hydroxyoctadecanoate
  • Dextran Sulfate