Department of Food Science and Nutrition, University of Minnesota, Twin Cities, MN, 55455, USA.
Clinical Translational Science Institute, University of Minnesota, Twin Cities, MN, 55455, USA.
Int J Obes (Lond). 2021 Jan;45(1):143-154. doi: 10.1038/s41366-020-00712-2. Epub 2020 Nov 19.
Lipocalin 2 (Lcn2), as an antimicrobial peptide is expressed in intestine, and the upregulation of intestinal Lcn2 has been linked to inflammatory bowel disease. However, the role of Lcn2 in shaping gut microbiota during diet-induced obesity (DIO) remains unknown. We found that short-term high fat diet (HFD) feeding strongly stimulates intestinal Lcn2 expression and secretion into the gut lumen. As the HFD feeding prolongs, fecal Lcn2 levels turn to decrease. Lcn2 deficiency accelerates the development of HFD-induced intestinal inflammation and microbiota dysbiosis. Moreover, Lcn2 deficiency leads to the remodeling of microbiota-derived metabolome, including decreased production of short-chain fatty acids (SCFAs) and SCFA-producing microbes. Most importantly, we have identified Lcn2-targeted bacteria and microbiota-derived metabolites that potentially play roles in DIO and metabolic dysregulation. Correlation analyses suggest that Lcn2-targeted Dubosiella and Angelakisella have a novel role in regulating SCFAs production and obesity. Our results provide a novel mechanism involving Lcn2 as an antimicrobial host factor in the control of gut microbiota symbiosis during DIO.
脂质运载蛋白 2（Lcn2）作为一种抗菌肽在肠道中表达，肠道 Lcn2 的上调与炎症性肠病有关。然而，Lcn2 在饮食诱导肥胖（DIO）期间塑造肠道微生物群中的作用尚不清楚。我们发现，短期高脂肪饮食（HFD）喂养强烈刺激肠道 Lcn2 的表达和分泌到肠道腔中。随着 HFD 喂养时间的延长，粪便 Lcn2 水平下降。Lcn2 缺乏会加速 HFD 诱导的肠道炎症和微生物群落失调的发展。此外，Lcn2 缺乏导致源自微生物群的代谢组的重塑，包括短链脂肪酸（SCFA）的产生减少和产生 SCFA 的微生物减少。最重要的是，我们已经确定了 Lcn2 靶向细菌和源自微生物群的代谢物，它们可能在 DIO 和代谢失调中发挥作用。相关性分析表明，Lcn2 靶向的 Dubosiella 和 Angelakisella 在调节 SCFA 产生和肥胖方面具有新的作用。我们的结果提供了一种新的机制，涉及 Lcn2 作为 DIO 期间控制肠道微生物群共生的抗菌宿主因子。
