INTERNATIONAL CONGRESS OF
CancerGenetics
Fecal extracellular vesicles as emerging mediators in microbiome–host communication and cancer metabolomics: a comprehensive review
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Zahra seifi,1,*
1. Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran
- Introduction: Extracellular vesicles (EVs) are tiny particles encased in a lipid bilayer, released by living organisms such as eukaryotes, bacteria, and archaea. They carry a variety of bioactive materials derived from the parent cell, including DNA, RNA, proteins, and metabolites, which can be involved in various physiological functions within a biological system. As a result, EVs and their contents may be crucial for communication between cells and across different kingdoms, including interactions between the microbiome and the host that are linked to cancer development. While cancer metabolomics studies have mostly focused on EVs from blood serum or urine, there has been little exploration of EVs obtained from fecal samples.
- Methods: A comprehensive literature search was conducted across PubMed, Scopus, and Web of Science to identify studies published up to 2025 that focused on EVs derived from fecal samples and their role in cancer. Keywords included “extracellular vesicles,” “fecal EVs,” “microbiome,” and “cancer metabolomics.” Both original research and review articles were screened, prioritizing studies addressing molecular cargo (proteins, RNAs, metabolites) and their impact on host–microbiome interactions. Articles not written in English or lacking experimental or clinical relevance were excluded. Data were synthesized to highlight current methodologies, knowledge gaps, and the potential of fecal EV profiling as a non-invasive biomarker source in cancer research.
- Results: Fecal EVs comprise elements from host and the gut microbiota. Studies have shown an enrichment of amino acids such as glutamic acid, phenylalanine, aspartate, and the aromatic alcohol indole-3-ethanol in fecal EVs from patients with solid tumors, including colorectal cancer. The metabolism of amino acids is frequently modified in cancerous conditions. In our investigation, glutamate emerged as the most significantly enriched and differentially abundant metabolite in EVs derived from patients with solid tumors, followed by phenylalanine and aspartate. Glutamate may influence cancer progression through the modulation of various cellular signaling pathways under ex vivo and in vitro conditions. Increased levels of glutamate have been documented in the cancerous tissues of patients diagnosed with pancreatic ductal adenocarcinoma, breast cancer, and prostate cancer. Within the realm of breast cancer research, phenylalanine has been identified as a compound that can convert into mutagenic, genotoxic, or carcinogenic entities, such as phenols and indoles, in breast tissue. Additionally, fecal metabolomic studies have established a link between phenylalanine metabolism and gut dysbiosis in murine models, demonstrating its association with inflammation and oxidative stress. Aspartate plays a pivotal role in cancer cell metabolism, being crucial for both protein and nucleotide biosynthesis, as well as for maintaining redox balance within cancer cells. Studies demonstrated that levels of N-acetylneuraminate, N-acetyl-glucosamine, and indole-3-ethanol were significantly reduced in the fecal extracellular vesicles of patients with solid tumors. N-acetylneuraminic acid, which is a major form of sialic acid, is crucial for cellular interactions and has been recognized as a tumor marker in the serum of individuals with head and neck cancer. Targeting sialic acids could be an effective strategy for cancer treatment, as demonstrated by tumor-inhibiting sialic acid mimetics in live models. Changes in cell surface glycans are essential to the process of cancer development. One study revealed that diminishing glycosylation of O-linked β-N-acetyl glucosamine disrupts glutamine metabolism, leading to a notable decrease in cell proliferation and tumor growth in mouse models of pancreatic ductal adenocarcinoma. In a similar vein, intraperitoneal administration of N-acetyl-D-glucosamine in a breast cancer xenograft model resulted in reduced cell proliferation and smaller tumors, along with decreased mitosis and lower angiogenesis when compared to control groups. Indole-3-ethanol, a metabolite derived from tryptophan, may affect host physiology by being absorbed through the intestinal lining and entering the systemic circulation, showcasing anti-oxidative and anti-inflammatory effects. An examination of the human gut microbiome and cytokine responses in whole blood indicated a negative correlation between the production of interferon-gamma (IFNγ) and bacterial genes that transform tryptophan into indole-3-ethanol, suggesting that indole-3-ethanol may possess anti-inflammatory qualities.
- Conclusion: The important metabolomic profiles discovered through fecal EVs in individuals with solid tumors offer significant insights that may inform future targeted investigations. Our results reinforce the notion that the metabolic profiles of fecal EVs should be incorporated into oncobiome studies, as they may act as non-invasive biomarkers for solid tumors, presenting new opportunities for diagnostic and therapeutic strategies.
- Keywords: Gut microbiome, Extracellular vesicles, Cancer
