Lipocalin 2 deficiency restrains aging-related reshaping of gut microbiota structure and metabolism

Xiaoxue Qiu, Chi Chen, Xiaoli Chen

Research output: Contribution to journalArticlepeer-review

Abstract

Gut microbiota modulate age-associated changes in metabolism, innate immune re-sponses, and cognitive function. However, the involvement of host factors in the regulation of age-dependent gut microbial structure and intestinal inflammation is largely unknown. Lipocalin 2 (Lcn2) has previously been identified as an adipocytokine and characterized as an important regu-lator of diet-induced obesity and inflammation. Previous studies have shown that Lcn2 plays a role in high fat diet-induced reshaping of gut microbiota and intestinal inflammation. However, the role of Lcn2 in the regulation of aging-related reshaping of gut microbiota is unclear. Herein, we demon-strate that fecal levels of Lcn2 are reduced during aging. Age reshaped gut microbiota composition in wild-type (WT) mice. Interestingly, Lcn2 deficiency diminished this effect of aging in Lcn2 knock-out (LKO) mice, leading to decreased bacterial diversity and increased Firmicutes to Bacteroidetes (F to B) ratio. Specifically, we identified 16 bacteria at the family level that were differentially abun-dant between WT and LKO mice at old age. Several health-promoting bacteria, including SCFA-producing bacteria, were significantly less prevalent in old LKO mice compared to WT mice, indi-cating that Lcn2 deficiency shifts the aging-related gut microbial community towards an unhealthy population and lowers microbial butyrate production. Our results provide a line of evidence that Lcn2 plays a role in the control of aging-related reshaping of gut microbiota composition and me-tabolites.

Original languageEnglish (US)
Article number1286
JournalBiomolecules
Volume11
Issue number9
DOIs
StatePublished - Sep 2021

Bibliographical note

Funding Information:
This research was funded by NIDDK Grant (R01 DK123042) awarded to X.C., the Doctoral Dissertation Fellowship from the University of Minnesota to X.Q., Allen Foundation Grant awarded to X.C., and the General Mills Foundation Chair in Genomics for Healthful Foods to X.C.

Publisher Copyright:
© 2021 by the authors. Li-censee MDPI, Basel, Switzerland.

Keywords

  • Aging
  • Gut microbiota
  • Inflammation
  • Lipocalin 2

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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