Identification of gut microbiota and microbial metabolites regulated by an antimicrobial peptide lipocalin 2 in high fat diet-induced obesity.
Identification of gut microbiota and microbial metabolites regulated by an antimicrobial peptide lipocalin 2 in high fat diet-induced obesity.
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DOI：
10.1038/s41366-020-00712-2
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发表时间：
2021-01
期刊：
影响因子：
--
通讯作者：
Chen X
中科院分区：
文献类型：
--
作者：
Qiu X;Macchietto MG;Liu X;Lu Y;Ma Y;Guo H;Saqui-Salces M;Bernlohr DA;Chen C;Shen S;Chen X
Lipocalin 2(Lcn2)作为一种抗菌肽在肠道中表达，肠道Lcn2表达上调与炎症性肠病有关。然而，Lcn2在饮食诱导肥胖(DIO)过程中形成肠道微生物区系的作用仍不清楚。我们发现，短期高脂饮食(HFD)喂养强烈刺激肠道Lcn2的表达和分泌到肠腔。随着HFD喂养时间的延长，粪便Lcn2水平呈下降趋势。Lcn2缺乏加速了HFD诱导的肠道炎症和微生物区系失调的发展。此外，Lcn2缺乏导致微生物区系代谢组的重塑，包括短链脂肪酸(SCFA)和产生SCFA的微生物的减少。最重要的是，我们已经确定了针对Lcn2的细菌和微生物衍生的代谢物，它们可能在DIO和代谢失调中发挥作用。相关分析表明，以Lcn2为靶标的Dubosiella和Angelakisella在调节SCFAs的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，使Lcn2作为一种抗微生物宿主因子在DIO期间控制肠道微生物区系共生。
Lipocalin 2 (Lcn2), as an anti-microbial 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 anti-microbial host factor in the control of gut microbiota symbiosis during DIO.
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