Dysosmobacter welbionis effects on glucose, lipid, and energy metabolism are associated with specific bioactive lipids

Abstract

The newly identified bacterium Dysosmobacter welbionis J115T improves host metabolism in high-fat diet (HFD)-fed mice. To investigate mechanisms, we used targeted lipidomics to identify and quantify bioactive lipids produced by the bacterium in the culture medium, the colon, the brown adipose tissue (BAT), and the blood of mice. In vitro, we compared the bioactive lipids produced by D. welbionis J115T versus the probiotic strain Escherichia coli Nissle 1917. D. welbionis J115T administration reduced body weight, fat mass gain, and improved glucose tolerance and insulin resistance in HFD-fed mice. In vitro, 19 bioactive lipids were highly produced by D. welbionis J115T as compared to Escherichia coli Nissle 1917. In the plasma, 13 lipids were significantly changed by the bacteria. C18-3OH was highly present at the level of the bacteria, but decreased by HFD treatment in the plasma and normalized in D. welbionis J115T–treated mice. The metabolic effects were associated with a lower whitening of the BAT. In the BAT, HFD decreased the 15-deoxy-Δ12,14-prostaglandin J2, a peroxisome proliferator–activated receptor (PPAR-γ) agonist increased by 700% in treated mice as compared to HFD-fed mice. Several genes controlled by PPAR-γ were upregulated in the BAT. In the colon, HFD-fed mice had a 60% decrease of resolvin D5, whereas D. welbionis J115T–treated mice exhibited a 660% increase as compared to HFD-fed mice. In a preliminary experiment, we found that D. welbionis J115T improves colitis. In conclusion, D. welbionis J115T influences host metabolism together with several bioactive lipids known as PPAR-γ agonists.