Key Laboratory of Molecular Animal Nutrition, Ministry of Education, National Engineering Laboratory for Feed Safety and Pollution Prevention and Controlling, Key Laboratory of Animal Nutrition and Feed Science (Eastern of China), Ministry of Agriculture and Rural Affairs, Key Laboratory of Animal Feed and Nutrition of Zhejiang Province, Institute of Feed Science, Zhejiang University, Hangzhou 310058, PR China.
School of Life Sciences, Northwestern Polytechnical University, Xi'an 710072, China.
J Adv Res. 2023 Oct;52:203-218. doi: 10.1016/j.jare.2023.08.003. Epub 2023 Aug 5.
Auricularia auricula is a well-known traditional edible and medical fungus with high nutritional and pharmacological values, as well as metabolic and immunoregulatory properties. Nondigestible fermentable polysaccharides are identified as primary bioactive constituents of Auricularia auricula extracts. However, the exact mechanisms underlying the effects of Auricularia auricula polysaccharides (AAP) on obesity and related metabolic endpoints, including the role of the gut microbiota, remain insufficiently understood.
The effects of AAP on obesity were assessed within high-fat diet (HFD)-based mice through obesity trait analysis and metabolomic profiling. To determine the mechanistic role of the gut microbiota in observed anti-obesogenic effects AAP, faecal microbiota transplantation (FMT) and pseudo-germ-free mice model treated with antibiotics were also applied, together with 16S rRNA genomic-derived taxonomic profiling.
High-fat diet (HFD) murine exposure to AAP thwarted weight gains, reduced fat depositing and enhanced glucose tolerance, together with upregulating thermogenesis proteomic biomarkers within adipose tissue. Serum metabolome indicated these effects were associated with changes in fatty acid metabolism. Intestine-dwelling microbial population assessments discovered that AAP selectively enhanced Papillibacter cinnamivorans, a commensal bacterium with reduced presence in HFD mice. Notably, HFD mice treated with oral formulations of P. cinnamivorans attenuated obesity, which was linked to decreased intestinal lipid transportation and hepatic thermogenesis. Mechanistically, it was demonstrated that P. cinnamivorans regulated intestinal lipids metabolism and liver thermogenesis by reducing the proinflammatory response and gut permeability in a JAK-STAT signaling-related manner.
Datasets from the present study show that AAP thwarted dietary-driven obesity and metabolism-based disorders by regulating intestinal lipid transportation, a mechanism that is dependent on the gut commensal P. cinnamivorans. These results indicated AAP and P. cinnamivorans as newly identified pre- and probiotics that could serve as novel therapeutics against obesity.
银耳是一种著名的传统食用和药用真菌,具有很高的营养价值和药理作用,以及代谢和免疫调节特性。不可消化的发酵多糖被认为是银耳提取物的主要生物活性成分。然而,银耳多糖(AAP)对肥胖和相关代谢终点的影响的确切机制,包括肠道微生物群的作用,仍知之甚少。
通过肥胖特征分析和代谢组学分析,在高脂肪饮食(HFD)基础上的小鼠中评估 AAP 对肥胖的影响。为了确定肠道微生物群在观察到的抗肥胖作用 AAP 中的机制作用,还应用了粪便微生物群移植(FMT)和抗生素处理的假无菌小鼠模型,以及 16S rRNA 基因组衍生的分类分析。
高脂肪饮食(HFD)暴露于 AAP 的小鼠体重增加受阻,脂肪沉积减少,葡萄糖耐量增强,同时脂肪组织中上调了产热蛋白组生物标志物。血清代谢组学表明,这些作用与脂肪酸代谢的变化有关。肠道驻留微生物种群评估发现,AAP 选择性地增强了 Papillibacter cinnamivorans,一种在 HFD 小鼠中存在减少的共生菌。值得注意的是,用 P. cinnamivorans 的口服制剂治疗 HFD 小鼠可减轻肥胖,这与肠道脂质转运和肝脏产热减少有关。从机制上讲,已经证明 P. cinnamivorans 通过降低促炎反应和肠道通透性来调节肠道脂质代谢和肝脏产热,这与 JAK-STAT 信号相关。
本研究的数据表明,AAP 通过调节肠道脂质转运来阻止饮食驱动的肥胖和代谢紊乱,这种机制依赖于肠道共生菌 P. cinnamivorans。这些结果表明 AAP 和 P. cinnamivorans 作为新发现的益生菌和预益生菌,可以作为肥胖的新型治疗药物。