In recent years, the role of gut microbial metabolites on the inhibition and progression of cancer has gained significant interest in anticancer research. It has been established that the gut microbiome plays a pivotal role in the development, treatment and prognosis of different cancer types which is often mediated through the gut microbial metabolites. For instance, gut microbial metabolites including bacteriocins, short-chain fatty acids and phenylpropanoid-derived metabolites have displayed direct and indirect anticancer activities through different molecular mechanisms. Despite the reported anticancer activity, some gut microbial metabolites including secondary bile acids have exhibited pro-carcinogenic properties. This review draws a critical summary and assessment of the current studies demonstrating the carcinogenic and anticancer activity of gut microbial metabolites and emphasises the need to further investigate the interactions of these metabolites with the immune system as well as the tumour microenvironment in molecular mechanistic and clinical studies. Graphical abstract

The complex association between the gut microbiome and cancer development has been an emerging field of study in recent years. The gut microbiome plays a crucial role in the overall maintenance of human health and interacts closely with the host immune system to prevent and fight infection. This review was designed to draw a comprehensive assessment and summary of recent research assessing the anticancer activity of the metabolites (produced by the gut microbiota) specifically against breast cancer. In this review, a total of 2701 articles were screened from different scientific databases (PubMed, Scopus, Embase and Web of Science) with 72 relevant articles included based on the predetermined inclusion and exclusion criteria. Metabolites produced by the gut microbial communities have been researched for their health benefits and potential anticancer activity. For instance, the short-chain fatty acid, butyrate, has been evaluated against multiple cancer types, including breast cancer, and has demonstrated anticancer potential via various molecular pathways. Similarly, nisin, a bacteriocin, has presented with a range of anticancer properties primarily against gastrointestinal cancers, with nominal evidence supporting its use against breast cancer. Comparatively, a natural purine nucleoside, inosine, though it has not been thoroughly investigated as a natural anticancer agent, has shown promise in recent studies. Additionally, recent studies demonstrated that gut microbial metabolites influence the efficacy of standard chemotherapeutics and potentially be implemented as a combination therapy. Despite the promising evidence supporting the anticancer action of gut metabolites on different cancer types, the molecular mechanisms of action of this activity are not well established, especially against breast cancer and warrant further investigation. As such, future research must prioritise determining the dose-response relationship, molecular mechanisms, and conducting animal and clinical studies to validate in vitro findings. This review also highlights the potential future directions of this field.

Cannabis, renowned for its historical medicinal use, harbours various bioactive compounds—cannabinoids, terpenes, and flavonoids. While major cannabinoids like delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) have received extensive scrutiny for their pharmacological properties, emerging evidence underscores the collaborative interactions among these constituents, suggesting a collective therapeutic potential. This comprehensive review explores the intricate relationships and synergies between cannabinoids, terpenes, and flavonoids in cannabis. Cannabinoids, pivotal in cannabis’s bioactivity, exhibit well-documented analgesic, anti-inflammatory, and neuroprotective effects. Terpenes, aromatic compounds imbuing distinct flavours, not only contribute to cannabis’s sensory profile but also modulate cannabinoid effects through diverse molecular mechanisms. Flavonoids, another cannabis component, demonstrate anti-inflammatory, antioxidant, and neuroprotective properties, particularly relevant to neuroinflammation. The entourage hypothesis posits that combined cannabinoid, terpene, and flavonoid action yields synergistic or additive effects, surpassing individual compound efficacy. Recognizing the nuanced interactions is crucial for unravelling cannabis’s complete therapeutic potential. Tailoring treatments based on the holistic composition of cannabis strains allows optimization of therapeutic outcomes while minimizing potential side effects. This review underscores the imperative to delve into the intricate roles of cannabinoids, terpenes, and flavonoids, offering promising prospects for innovative therapeutic interventions and advocating continued research to unlock cannabis’s full therapeutic potential within the realm of natural plant-based medicine.

Australian native plants have adapted themselves to harsh climatic conditions enabling them to produce unique and high levels of secondary metabolites. Native fruits and vegetables have been an integral part of the Indigenous Australian diet and Bush medicine for centuries. They have recently gained popularity owing to their rich dietary fiber, minerals, polyphenolic and antioxidant contents. This review presents a comprehensive summary and critical assessment of the studies performed in the last few decades to understand the phytochemical and nutritional profiles and therapeutic properties of Australian native fruits and vegetables. Furthermore, the potential of these fruits and vegetables as functional food ingredients and in the prevention and treatment of different diseases is discussed. Research on the nutritional and phytochemical profiles and therapeutic activity of Australian vegetables is limited with most studies focused on native fruits. These fruits have demonstrated promising antioxidant, anticancer, anti-inflammatory and antimicrobial activities mostly in in vitro models. More research to a) identify novel bioactive compounds, b) define optimal post-harvest and extraction methods, and c) understand molecular mechanisms of pharmacological activity through preclinical and clinical studies is prudent for the prospective and wider use of Australian native fruits and vegetables by the food, pharmaceutical, and nutraceutical industries.

The gut microbiota undergoes metabolic processes to produce by-products (gut metabolites), which play a vital role in the overall maintenance of health and prevention of disease within the body. However, the use of gut metabolites as anticancer agents and their molecular mechanisms of action are largely unknown. Therefore, this study evaluated the anti-proliferative effects of three key gut microbial metabolites—sodium butyrate, inosine, and nisin, against MCF7 and MDA-MB-231 breast adenocarcinoma cell lines. To determine the potential mechanistic action of these gut metabolites, flow cytometric assessments of apoptotic potential, reactive oxygen species (ROS) production measurements and proteomics analyses were performed. Sodium butyrate exhibited promising cytotoxicity, with IC₅₀ values of 5.23 mM and 5.06 mM against MCF7 and MDA-MB-231 cells, respectively. All three metabolites were found to induce apoptotic cell death and inhibit the production of ROS in both cell lines. Nisin and inosine indicated a potential activation of cell cycle processes. Sodium butyrate indicated the possible initiation of signal transduction processes and cellular responses to stimuli. Further investigations are necessary to ascertain the effective therapeutic dose of these metabolites, and future research on patient-derived tumour spheroids will provide insights into the potential use of these gut metabolites in cancer therapy.