Astaxanthin Alleviates Intestinal Ferroptosis through Gut Commensal Lepagella muris-Mediated Retinoic Acid Production and SLC7A11 Activation.

Authors

Shuqi Liu, Liang Huang, Sai Xiao, Yige Li, Shiqi Luo, Erjia Hou, Yu Zhang, Mingliang Jin, Yizhen Wang, Xin Zong

Published in

Research (Washington, D.C.). Volume 9. Pages 1421. Epub Sep 02, 2026.

Abstract

Intestinal epithelial injury is increasingly linked to ferroptosis, yet how dietary bioactives engage the gut microbiota to restrain this process remains largely unresolved. Here, astaxanthin (ASTA) was identified as a microbiota-engaged regulator of intestinal ferroptosis and lipid peroxidation. ASTA markedly ameliorated dexamethasone-induced intestinal injury, and this protection was closely associated with the attenuation of epithelial ferroptosis. Depletion of the gut microbiota largely abolished the protective effect of ASTA, establishing the gut microbiota as an essential mediator of its intestinal bioactivity. Microbiome and metabolome profiling further revealed that ASTA reshaped the microbial metabolic landscape, with retinol metabolism emerging as a dominant pathway linked to ferroptosis resistance. Among the altered metabolites, retinoic acid was identified as a pivotal ASTA-associated metabolite that connected microbial remodeling with the restoration of epithelial anti-ferroptosis capacity. Metagenomics combined with in vitro bacterial metabolic assays identified Lepagella muris as a candidate ASTA-responsive bacterium capable of contributing to retinoic acid production. Mechanistically, retinoic acid protected intestinal epithelial cells from ferroptosis and barrier disruption through activation of SLC7A11, thereby reinforcing the anti-ferroptosis defense system. This study moves beyond the conventional view of ASTA as a direct antioxidant and reveals a microbiota-enabled redox metabolic mechanism that may be therapeutically exploited for ferroptosis-associated diseases.

PMID:
42688585
Bibliographic data and abstract were imported from PubMed on 13 Oct 2026.

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