SACM - United States of America

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    THE IMPACTS OF ANTHOCYANINS ON GUT HEALTH: MICROBIOME DYNAMICS AND COLORECTAL CANCER CELL RESPONSES
    (Utah State University, 2025) Almatani, Mohammed F; Benninghoff, Abby D
    Anthocyanin (ACN)-rich foods are believed to suppress gut inflammation and may reduce the risk of colitis-associated colorectal cancer (CAC) through direct interactions with the gut epithelium or by modulating the gut microbiome. The overarching goal of this research was to investigate the dynamic changes in gut microbiome composition in response to ACN-rich foods within the context of a Western diet and to assess the direct effects of pure anthocyanins and their aglycones on colon cancer cell lines representing different disease stages. In the first study, male C57BL/6J mice were fed TWD supplemented with freeze- dried, ACN-rich whole food powders. The results demonstrated distinct shifts in gut microbiome composition as early as one day after exposure. However, these changes were not sustained after cessation of the diet, indicating that consistency is critical for persistent effects. Correlation analyses revealed that the unique ACN profiles of each food source were associated with specific microbial shifts, highlighting the differential microbiome-modulating potential of ACNs based on their structural composition. The second study evaluated the cytotoxic effects of purified anthocyanins and their aglycones on human colon cancer cell lines (HT29 and HCT116) at physiologically relevant concentrations. Contrary to expectations, these compounds did not significantly affect cell viability, apoptosis, or cell cycle progression. These findings suggest that the anticancer effects observed with ACN-rich whole foods are unlikely to result from pure anthocyanins alone but may instead depend on synergistic interactions among multiple bioactive compounds and gut microbiome-derived metabolites. Collectively, this research provides an integrative understanding of ACN-rich foods by combining dynamic microbiome analysis with physiologically relevant cancer models. It underscores the importance of whole food matrices and supports the need for further investigation into the role of gut microbial metabolism in mediating the anti-inflammatory and anti-carcinogenic potential of dietary anthocyanins.
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    Field Cancerization and Microbiome Effects on Lung Cancer: A Source of Early Detection Biomarkers to Improve Patients’ Outcome
    (George Mason University, 2024-08-16) Alhammad, Rayan; Luchini, Alessandra
    Lung cancer results in more deaths than any other cancer in the United States and worldwide, with non-small cell lung cancer (NSCLC) accounting for most cases. Diagnosis typically involves chest imaging, molecular testing, and biopsy. However, most patients are diagnosed at advanced stages, with only a 6% chance of a 5-year survival rate. In contrast, early-stage diagnosis and treatment can result in a favorable prognosis, with a high 5-year survival rate of 70-90%. The concept of tumor field cancerization describes a phenomenon where exposure to carcinogens can cause histologic changes in large areas of tissue, creating a field of pre-malignant cells that can eventually develop into tumors. Additionally, microbiota dysbiosis might influence tumor development. Studies have identified several commensal bacteria present in the lower airway tracts, such as Streptococcus, Prevotella, and Veillonella. The high mortality rate of lung cancer is often attributed to i) its late-stage diagnosis, ii) aggressive nature given its ability to metastasize early in the disease process complicating treatment and reducing survival rates, and iii) significant therapeutic challenges despite current treatments such as surgery, chemotherapy, radiation therapy, targeted therapy and immunotherapy. Despite advancements, the survival rate for advanced lung cancer remains low. To address this challenge, our research focuses on identifying risk protein biomarkers that are associated with the earliest molecular changes indicative of an ongoing tumorigenic process, thus offering significant potential for early intervention. Our study investigates the phenotypic molecular changes in the bronchial tree of NSCLC patients in light of the field cancerization theory and correlates these findings with blood biomarkers to support the future development of a non-invasive risk assessment test. Using enhanced liquid chromatography tandem mass spectrometry (LC-MS/MS) proteomic analysis and two independent cohorts of lung cancer patients (N=18, and N=263) with matched plasma and bronchial tree tissue specimens, we identified a set of 6 and 13 candidate risk plasma biomarkers with tissue origin. Additionally, we explored the microbiome proteome composition in NSCLC patient tissue and plasma to support future characterization of its potential role in cancer development. Risk biomarkers will enable the evaluation of individuals at high risk, guiding necessary lifestyle adjustments and facilitating the development of personalized prevention plans and therapies.
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