Metabolome-microbiome convergence under circadian disruption accelerates mammary tumorigenesis: multi-omics integration insights.

Authors

Mrinmoy Sarkar, Olajumoke Ogunlusi, Trenton Stewart, Efrat Muller, Erin H Seeley, Tapasree Roy Sarkar

Published in

BMC cancer. Jul 17, 2026. Epub Jul 17, 2026.

Abstract

Circadian rhythm disruption (CRD), common in shift work and jet lag, promotes mammary tumorigenesis through coordinated reprogramming of tumor metabolism and the local microbiome. CRD increased immunosuppressive metabolites - kynurenic acid, spermidine, and argininosuccinic acid - that suppressed effector T-cell activity and drove macrophage polarization toward anti-inflammatory phenotypes. 16S rRNA sequencing revealed enrichment of immune-modulatory Firmicutes and Bacilli within CRD tumors. Experimental and multi-omics integrative analyses strongly support metabolome-microbiome crosstalk driving immune suppression under CRD. Inhibition of arginase-1 (ARG1) with nor-NOHA restored cytotoxic T-cell responses and reduced lung metastases. These findings establish metabolome-microbiome interactions as a central mechanism of CRD-induced immunosuppression and metastasis, revealing potential therapeutic targets for circadian disruption-associated breast cancer.

PMID:
42469677
Bibliographic data and abstract were imported from PubMed on 18 Jul 2026.

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