BMC cancerJul 17, 2026

Changes in body and gut chemicals during disrupted daily rhythms may speed up breast cancer development

Circadian Biology Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jul 18, 2026

Abstract

Circadian rhythm disruption (CRD) is associated with increased levels of immunosuppressive metabolites that may promote mammary tumor growth.

CRD was linked to higher levels of kynurenic acid, spermidine, and argininosuccinic acid, which suppressed effector T-cell activity.
Macrophages within CRD tumors showed a shift toward anti-inflammatory phenotypes.
16S rRNA sequencing indicated an increase in immune-modulatory Firmicutes and Bacilli in tumors from CRD conditions.
Experimental analyses support the idea of crosstalk between metabolites and the microbiome contributing to immune suppression under CRD.
Inhibition of arginase-1 with nor-NOHA restored T-cell responses and decreased lung metastases.

Simplified

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.