Moens de Hase Emilie, Petitfils Camille, Alhouayek Mireille, Depommier Clara, Le Faouder Pauline, Delzenne Nathalie M, Van Hul Matthias, Muccioli Giulio G, Cenac Nicolas, Cani Patrice D
Metabolism and Nutrition Research group, Louvain Drug Research Institute (LDRI), UCLouvain, Université catholique de Louvain, Brussels, Belgium; WELBIO-Walloon Excellence in Life Sciences and Biotechnology, WELBIO department, WEL Research Institute, Wavre, Belgium.
IRSD, INSERM, INRA, INP-ENVT, Toulouse University 3 Paul Sabatier, Toulouse, France.
J Lipid Res. 2023 Oct;64(10):100437. doi: 10.1016/j.jlr.2023.100437. Epub 2023 Aug 28.
The newly identified bacterium Dysosmobacter welbionis J115 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 J115 versus the probiotic strain Escherichia coli Nissle 1917. D. welbionis J115 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 J115 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 J115-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 J115-treated mice exhibited a 660% increase as compared to HFD-fed mice. In a preliminary experiment, we found that D. welbionis J115 improves colitis. In conclusion, D. welbionis J115 influences host metabolism together with several bioactive lipids known as PPAR-γ agonists.
新鉴定出的细菌韦氏迪索氏菌J115可改善高脂饮食（HFD）喂养小鼠的宿主代谢。为了探究其机制，我们使用靶向脂质组学来鉴定和定量该细菌在培养基、结肠、棕色脂肪组织（BAT）和小鼠血液中产生的生物活性脂质。在体外，我们比较了韦氏迪索氏菌J115与益生菌菌株大肠杆菌Nissle 1917产生的生物活性脂质。给予韦氏迪索氏菌J115可减轻HFD喂养小鼠的体重、脂肪量增加，并改善葡萄糖耐量和胰岛素抵抗。在体外，与大肠杆菌Nissle 1917相比，韦氏迪索氏菌J115大量产生19种生物活性脂质。在血浆中，13种脂质因该细菌而发生显著变化。C18-3OH在细菌水平上含量很高，但在血浆中经HFD处理后降低，而在经韦氏迪索氏菌J115处理的小鼠中恢复正常。这些代谢效应与BAT较低的白化程度有关。在BAT中，HFD降低了15-脱氧-Δ12,14-前列腺素J2，与HFD喂养的小鼠相比，经处理的小鼠中该过氧化物酶体增殖物激活受体（PPAR-γ）激动剂增加了700%。BAT中受PPAR-γ控制的几个基因上调。在结肠中，HFD喂养的小鼠中消退素D5减少了60%，而与HFD喂养的小鼠相比，经韦氏迪索氏菌J115处理的小鼠中消退素D5增加了660%。在一项初步实验中，我们发现韦氏迪索氏菌J115可改善结肠炎。总之，韦氏迪索氏菌J115与几种已知为PPAR-γ激动剂的生物活性脂质一起影响宿主代谢。
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