ArticleCancers2019
Lithocholic Acid, a Metabolite of the Microbiome, Increases Oxidative Stress in Breast Cancer.
Article in Cancers, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
82 citing papers in PubMed, 1 synthesis or guideline pooled it, 111 citations in OpenAlex.
- Pooled it
- Gut microbiota-derived metabolites as context-dependent modulators of Nrf2 signaling in inflammation-driven carcinogenesis.Gut microbes · 2026Review
- Deciphering the intratumor microbiota in malignant gastrointestinal tumors: multifaceted interplay and clinical implications.Cell communication and signaling : CCS · 2026Review
- Intratumoral microbiota and metabolites: dual roles in cancer progression and therapeutic opportunities.Cell communication and signaling : CCS · 2026Review
- The dialogue between breast cancer and microorganisms.Frontiers in cellular and infection microbiology · 2026Review
- Gut metabolites: key factors in the cross-talk between the gut microbiota and tumor immunotherapy.Frontiers in immunology · 2026Review
- Vitamin BCommunications biology · 2025Article
- Metagenomic analyses reveal E. coli-derived siderophores as potential signatures for breast cancer.Journal of translational medicine · 2025Article
- G protein-coupled receptors as novel therapeutic targets in non-small-cell lung cancer.Medical review (2021) · 2025Review
- Causal Effects of Plasma Metabolites on Leukemia: A Mendelian Randomization Study.Metabolites · 2025Article
- Microbiome-targeted nanoplatforms and engineering approaches in breast cancer therapy.Molecular cancer · 2025Review
- Mammary Gland Microbiota in Benign Breast Diseases.International journal of molecular sciences · 2025Review
- The microbiome in cancer.iMeta · 2025Review
- Bacteria-Based Roles in Solid Tumors: Potential for Prevention and Treatment.Pathogens (Basel, Switzerland) · 2025Review
- Circulating bile acid profiles characteristics and the potential predictive role in clear cell renal cell carcinoma progression.BMC nephrology · 2025Article
- Ursodeoxycholic acid prompts glycolytic dominance, reductive stress and epithelial-to-mesenchymal transition in ovarian cancer cells through NRF2 activation.Cell death discovery · 2025Article
- Maternal dietary inulin intake during late gestation and lactation ameliorates intestinal oxidative stress in piglets with the involvements of gut microbiota and bile acids metabolism.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2025Article
- Interplay between bile acids, gut microbiota, and the tumor immune microenvironment: mechanistic insights and therapeutic strategies.Frontiers in immunology · 2025Review
- The microbiota in breast cancer: dysbiosis, microbial metabolites, and therapeutic implications.American journal of cancer research · 2025Review
- The interaction network between intestinal flora and cell death in microecosystem of pan-cancers.International journal of medical sciences · 2025Review
22 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
18 authors at 2 institutions in 2 countries.
Funding
Abstract
In breast cancer patients, the diversity of the microbiome decreases, coinciding with decreased production of cytostatic bacterial metabolites like lithocholic acid (LCA). We hypothesized that LCA can modulate oxidative stress to exert cytostatic effects in breast cancer cells. Treatment of breast cancer cells with LCA decreased nuclear factor-2 (NRF2) expression and increased Kelch-like ECH associating protein 1 (KEAP1) expression via activation of Takeda G-protein coupled receptor (TGR5) and constitutive androstane receptor (CAR). Altered NRF2 and KEAP1 expression subsequently led to decreased expression of glutathione peroxidase 3 (GPX3), an antioxidant enzyme, and increased expression of inducible nitric oxide synthase (iNOS). The imbalance between the pro- and antioxidant enzymes increased cytostatic effects via increased levels of lipid and protein oxidation. These effects were reversed by the pharmacological induction of NRF2 with RA839, tBHQ, or by thiol antioxidants. The expression of key components of the LCA-elicited cytostatic pathway (iNOS and 4HNE) gradually decreased as the breast cancer stage advanced. The level of lipid peroxidation in tumors negatively correlated with the mitotic index. The overexpression of iNOS, nNOS, CAR, KEAP1, NOX4, and TGR5 or the downregulation of NRF2 correlated with better survival in breast cancer patients, except for triple negative cases. Taken together, LCA, a metabolite of the gut microbiome, elicits oxidative stress that slows down the proliferation of breast cancer cells. The LCA-oxidative stress protective pathway is lost as breast cancer progresses, and the loss correlates with poor prognosis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.