Inhibitory Effects of Differentially Cultivated Carrots on AOM/DSS-Induced Colorectal Cancer Via Modulation of Inflammation, Apoptosis, and Gut Microbiota

Background: Carrot (Daucus carota) is a widely consumed vegetable rich in dietary fibre, vitamins, minerals, and antioxidant compounds. Carrots contain fibre and bioactive phytochemicals that have been associated with anti-inflammatory and anti-proliferative activities in preclinical settings. Beta-carotene, a prominent carotenoid in carrots, has been reported to modulate immune-related pathways in experimental models; however, the extent to which these observations translate to reduced colorectal cancer risk in humans remains to be determined. Objective: This study investigated whether cultivation methods influence the bioactivity of carrot extracts in an azoxymethane/dextran sodium sulfate (AOM/DSS)-induced murine model of colitis-associated colon tumorigenesis, with emphasis on apoptosis-related markers, inflammatory responses, and gut microbiota alterations. Methods: Six-week-old male C57BL/6 mice (~20 g) were maintained under SPF conditions (12-h light/dark cycle; 23 ± 2 °C; 50 ± 5% humidity). After one week of acclimatisation with ad libitum food and water, mice were randomly allocated to six groups (n = 10/group). The normal and AOM/DSS control groups received saline, whereas the Conventional Fertiliser Carrot (CFC), Seawater Fertiliser Carrot (SFC), Trace Element Fertiliser Carrot (TFC), and Deep-sea Water Mineral fertiliser carrot (NFC) groups received the respective carrot extracts (50 mg/mL). Total phenolic and total flavonoid contents were quantified and analysed using GraphPad Prism 9.4.1. Results: Among the cultivation conditions tested, carrots produced with deep-sea water mineral fertiliser (NFC) were associated with increased expression of apoptosis-related genes and proteins in colon tissue, including p53, p21, Bim, Bad, Bax, Bak, Caspase-9, and Caspase-3. NFC treatment was also associated with lower levels of pro-inflammatory cytokines and mediators (TNF-α, IL-1β, IL-6, IFN-γ, NF-κB, and iNOS) measured across serum, spleen cells, and liver tissues. Gut microbiota profiling indicated a compositional shift in carrot-treated mice relative to controls, including increased relative abundance of taxa previously linked to anti-inflammatory or anti-tumour-associated profiles (e.g., Lachnospiraceae and Mucispirillum schaedleri). Conclusion: In this AOM/DSS mouse model, carrot extracts—particularly those derived from carrots cultivated with deep-sea water mineral fertiliser—were associated with reduced tumour-related endpoints alongside coordinated changes in apoptotic and inflammatory markers and gut microbiota composition. These findings support further investigation into cultivation-dependent differences in carrot bioactivity and encourage additional studies to clarify mechanisms and assess translational relevance in humans.