The gut microbiota in breast cancer development and treatment: The good, the bad, and the useful!

Gut Microbes, Journal Year: 2023, Volume and Issue: 15(1)

Published: June 12, 2023

Regardless of the global progress in early diagnosis and novel therapeutic regimens, breast carcinoma poses a devastating threat, advances are somewhat marred by high mortality rates. Breast cancer risk prediction models based on known factors extremely useful, but large number cancers develop women with no/low risk. The gut microbiome exerts profound impact host health physiology has emerged as pivotal frontier pathogenesis. Progress metagenomic analysis enabled identification specific changes microbial signature. In this review, we discuss metabolomic associated initiation metastatic progression. We summarize bidirectional various cancer-related therapies microbiota vice-versa. Finally, strategies to modulate toward more favorable state that confers anticancer effects.

Language: Английский

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Indole‐3‐Lactic Acid Inhibits Doxorubicin‐Induced Ferroptosis Through Activating Aryl Hydrocarbon Receptor/Nrf2 Signalling Pathway

Journal of Cellular and Molecular Medicine, Journal Year: 2025, Volume and Issue: 29(2)

Published: Jan. 1, 2025

ABSTRACT The clinical application of doxorubicin (DOX) is limited due to its cardiotoxicity, which primarily attributed interaction with iron in mitochondria, leading lipid peroxidation and myocardial ferroptosis. This study aimed investigate the role gut microbiota‐derived metabolite, indole‐3‐lactic acid (ILA), mitigating DOX‐induced cardiotoxicity (DIC). Cardiac function, pathological changes, ferroptosis were assessed vivo. cardioprotective effects mechanisms ILA explored using multi‐omics approaches, including single‐nucleus RNA sequencing (snRNA‐seq) bulk RNA‐seq, further validated Nrf2 knockout mice. findings revealed that DOX treatment disrupted microbiota, significantly reducing levels tryptophan metabolite ILA. In DIC models, supplementation markedly improved cardiac reduced collagen deposition, mitigated atrophy. snRNA‐seq analyses indicated played a crucial Experimental data demonstrated decreased both mice DOX‐treated H9C2 cells, evidenced by restoration GPX4 SLC7A11 reduction ACSL4. Mechanistically, functions as ligand for aryl hydrocarbon receptor (AhR), upregulation expression. protective against abolished silencing AhR. Moreover, beneficial on eliminated Nrf2‐deficient conclusion, exerts therapeutic inhibiting through activation AhR/Nrf2 signalling pathway. Identifying microbial could offer viable strategies DIC.

Language: Английский

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Akkermansia muciniphila: A potential target and pending issues for oncotherapy

Pharmacological Research, Journal Year: 2023, Volume and Issue: 196, P. 106916 - 106916

Published: Sept. 9, 2023

In the wake of development metagenomic, metabolomic, and metatranscriptomic approaches, intricate interactions between host various microbes are now being progressively understood. Numerous studies have demonstrated evident changes in gut microbiota during process a variety diseases, such as diabetes, obesity, aging, cancers. Notably, is viewed potential source novel therapeutics. Currently, Next-generation probiotics (NGPs) gaining popularity therapeutic agents that alter affect cancer development. Akkermansia muciniphila (A. muciniphila), representative commensal bacterium, has received substantial attention over past decade promising NGP. The components metabolites A. can directly or indirectly tumorigenesis, particular through its effects on antitumor immunosurveillance, including stimulation pattern recognition receptors (PRRs), which also leads to better outcomes situations, prevention curation this article, we systematically summarize role tumorigenesis (involving gastrointestinal non-gastrointestinal cancers) tumor therapy. particular, carefully discuss some critical scientific issues need be solved for future using beneficial bacterium treatment, might provide bright clues assistance application drugs targeting clinical oncotherapy.

Language: Английский

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The role of gut microbiota and metabolites in cancer chemotherapy

Journal of Advanced Research, Journal Year: 2023, Volume and Issue: 64, P. 223 - 235

Published: Nov. 26, 2023

The microbiota inhabits the epithelial surfaces of hosts, which influences physiological functions from helping digest food and acquiring nutrition to regulate metabolism shaping host immunity. With deep insight into microbiota, an increasing amount research reveals that it is also involved in initiation progression cancer. Intriguingly, gut can mediate biotransformation drugs, thereby altering their bioavailability, bioactivity, or toxicity. Review review aims elaborate on role microbial metabolites efficacy adverse effects chemotherapeutics. Furthermore, we discuss clinical potential various ways harness for cancer chemotherapy. Key Scientific Concepts Recent evidence shows modulates toxicity chemotherapy agents, leading diverse responses Thereinto, targeting improve diminish chemotherapeutic drugs may be a promising strategy tumor treatment.

Language: Английский

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Fusobacterium nucleatum: a novel immune modulator in breast cancer?

Expert Reviews in Molecular Medicine, Journal Year: 2023, Volume and Issue: 25

Published: Jan. 1, 2023

Abstract Breast cancer was the most commonly diagnosed worldwide in 2020. Greater understanding of factors which promote tumour progression, metastatic development and therapeutic resistance is needed. In recent years, a distinct microbiome has been detected breast, site previously thought to be sterile. Here, we review clinical molecular relevance oral anaerobic bacterium Fusobacterium nucleatum breast cancer. F. enriched tissue compared with matched healthy shown mammary growth progression mouse models. Current literature suggests that modulates immune escape inflammation within microenvironment, two well-defined hallmarks Furthermore, microbiome, specifically, affect patient response therapy including checkpoint inhibitors. These findings highlight areas future research needed better understand influence treatment

Language: Английский

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The microbiome: a link between obesity and breast cancer risk

Frontiers in Microbiomes, Journal Year: 2024, Volume and Issue: 3

Published: May 3, 2024

Globally, breast cancer is the leading cause of incidence and mortality among all female cancers. Hereditary factors only account for 5-10% cancers, highlighting importance non-hereditary factors, such as obesity. The increasing prevalence obesity underscores need to understand its contribution risk. Multiple mechanisms may mediate pro-carcinogenic effects obesity, including altered adipokine levels, local systemic inflammation, disruption insulin insulin-like growth factor signaling, increased estrogen alterations microbiome. In this review, we focus on link between gut microbiome risk in context First, discuss how influences Next, describe effect carcinogenesis, underlying molecular mechanisms. Finally, review preclinical data interactions host bacteria, current challenges study obesity-microbiome connection, future perspectives field.

Language: Английский

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Diet Modulates the Gut Microbiome, Metabolism, and Mammary Gland Inflammation to Influence Breast Cancer Risk

Cancer Prevention Research, Journal Year: 2024, Volume and Issue: 17(9), P. 415 - 428

Published: May 3, 2024

Abstract Several studies indicate a strong link between obesity and the risk of breast cancer. Obesity decreases gut microbial biodiversity modulates Bacteroidetes-to-Firmicutes phyla proportional abundance, suggesting that increased energy-harvesting capacity from indigestible dietary fibers elevated lipopolysaccharide bioavailability may promote inflammation. To address limited evidence linking diet-mediated changes in microbiota to cancer risk, we aimed determine how diet affects microbiome risk. For ten weeks, female 3-week-old BALB/c mice were fed six different diets (control, high-sugar, lard, coconut oil, lard + flaxseed safflower oil). Fecal 16S sequencing was performed for each group. Diet shifted fecal populations modulated mammary gland macrophage infiltration. Fecal-conditioned media polarity In our DMBA-induced model, differentially tumor metabolism. We demonstrated patterns change metabolic outcomes microbiota, possibly contributing Furthermore, showed influence on metabolism, inflammation, polarity. This study suggests dietary–microbiome interactions are key mediators Prevention Relevance: Our demonstrates impact focusing interplay diet, microbiome,

Language: Английский

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The Interplay between Microbiota and Chemotherapy-Derived Metabolites in Breast Cancer

Metabolites, Journal Year: 2023, Volume and Issue: 13(6), P. 703 - 703

Published: May 28, 2023

The most common cancer in women is breast cancer, which also the second leading cause of death this group. It is, however, important to note that some will develop or not regardless whether certain known risk factors are present. On other hand, compounds produced by bacteria gut, such as short-chain fatty acids, secondary bile and metabolites may be linked development mediate chemotherapy response. Modeling microbiota through dietary intervention identifying directly associated with its complications useful identify actionable targets improve effect antiangiogenic therapies. Metabolomics therefore a complementary approach metagenomics for purpose. As result combination both techniques, better understanding molecular biology oncogenesis can obtained. This article reviews recent literature about influence bacterial patients, well diet.

Language: Английский

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Gut microbiome influences incidence and outcomes of breast cancer by regulating levels and activity of steroid hormones in women

Cancer Reports, Journal Year: 2023, Volume and Issue: 6(11)

Published: June 13, 2023

Abstract Background Breast cancer, the leading cancer type in women worldwide, is affected by reproductive and nonreproductive factors. Estrogen progesterone influence incidence progression of breast cancer. The microbiome gut, a complex organ that plays vital role digestion homeostasis, enhances availability estrogen host. Thus, an altered gut may hormone‐induced incidence. This review describes current understanding roles influencing with emphasis on microbiome‐induced metabolism progesterone. Recent Findings Microbiome has been recognized as promising hallmark Next‐generation sequencing technologies have aided rapid identification components are capable metabolizing Moreover, studies indicated wider chemotherapeutic hormonal therapy agents reducing their efficacy patients predominant effect postmenopausal women. Conclusion variations its composition significantly alter outcomes healthy diverse required for better response to anticancer therapies. Finally, emphasizes requirement elucidate mechanisms aid improving composition, hence, survival

Language: Английский

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Bones and guts – Why the microbiome matters

Journal of bone oncology, Journal Year: 2024, Volume and Issue: 44, P. 100523 - 100523

Published: Jan. 5, 2024

The importance of the gut microbiota in human health has become increasingly apparent recent years, especially when relationship between and host is no longer symbiotic. It long been appreciated that dysbiosis can be detrimental to associated with numerous disease states. Only within last decade, however, was implicated bone biology. Dubbed osteomicrobiology, this emerging field aims understand microbiome microenvironment both disease. Importantly, key one major clinical challenges facing cancer biologists: metastasis, may lie osteomicrobiology; however link bacteria metastasis only beginning explored. This review will discuss (i) osteomicrobiology as an field, (ii) current understanding context bone.

Language: Английский

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