Identification of gut microbiota and microbial metabolites regulated by an antimicrobial peptide lipocalin 2 in high fat diet-induced obesity

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)143-154
Number of pages12
JournalInternational Journal of Obesity
Volume45
Issue number1
DOIs
StatePublished - Jan 2021

Bibliographical note

Funding Information:
Acknowledgements This work was supported by Allen Foundation Grant awarded to XC, the General Mills Foundation Chair in Genomics for Healthful Foods to XC, NIDDK Grant (R01 DK123042) awarded to XC, and the Doctoral Dissertation Fellowship from the University of Minnesota to XQ.

Publisher Copyright:
© 2020, The Author(s), under exclusive licence to Springer Nature Limited.

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