Abstract 3619: Red cabbage juice reprograms the gut microbiome and enhances butyrate production to prevent colorectal cancer

Abstract Background Colorectal cancer (CRC) remains the second leading cause of cancer-related mortality in the United States, with Western diet-induced gut dysbiosis implicated in its pathogenesis. Early interventions targeting the gut microbiome offer a promising prevention strategy. Dietary approaches that enhance short-chain fatty acid (SCFA) production like butyrate, have emerged as potential chemopreventive measures. This study investigated the preventive efficacy of red cabbage juice (RCJ) in a genetically engineered mouse model of CRC by examining its effects on microbial composition, butyrate production and its translational relevance using CRC patient-derived organoids (PDOs). Methods Tamoxifen inducible APCfl/fl;Cdx-CreER (AC) mice for CRC were randomized to receive either phosphate-buffered saline (PBS) or RCJ as oral gavage for 10 weeks. Then, mice were injected with tamoxifen to induce CRC and monitored for weight loss and diarrhea. At the endpoint, colon tissues and cecal contents were collected for immunohistochemistry (IHC), metagenomic profiling, and fecal SCFA quantification by GC-MS/MS. In parallel, PDOs from CRC patients were developed and treated with RCJ alone or in combination with chemotherapeutic agents oxaliplatin or 5-fluorouracil (5-FU) and monitored in real-time on an IncuCyte platform and therapy responses (proliferation and apoptosis) were evaluated by IHC. Results RCJ significantly reduced polyps and tumor progression in AC mice and improved survival compared to PBS group. Enhanced expression of mucosal protective mucins Muc2 and Muc4 in the colonic epithelium of RCJ-treated mice. Shotgun sequencing revealed enrichment of succinate-to-butyrate metabolic pathways, elevated fecal succinate, butyrate and abundance of butyrate-producing Clostridia etc. Treatment of PDOs with 6% RCJ inhibited PDO growth, number, size as analyzed by IncuCyte provided us with its translational relevance for CRC prevention. Further, RCJ and oxaliplatin combination therapy significantly reduced organoid number, size, area vs. RCJ alone, RCJ + 5-FU, or media control, suggesting that RCJ may enhance the therapeutic response of chemotherapy to combat CRC organoids growth. IHC images confirmed these effects, showing decreased proliferation, and increased apoptosis upon the treatment. Conclusions RCJ modulates the gut microbiome and enhances butyrate production, correlating with reduced tumor burden in a preclinical CRC model. It also exerts inhibitory effect on CRC PDO growth, number, size. Notably, RCJ enhances the efficacy of oxaliplatin in PDOs, suggesting its potential to overcome chemoresistance. These findings underscore the translational potential of RCJ as a dietary intervention targeting gut microbiome-SCFA interactions and an adjunctive chemopreventive agent in CRC prevention, particularly in at-risk surgical populations. Citation Format: Bineet Narayan, Yariswamy Manjunath, Nagabhhishek Sirpu Natesh, Chayanee Chanpanich, Parsa Ghadermazi, BLAKE ARCIGA, Samarth Kansara, Ajay Tosh, John Ulbrich, Mary Kate Grossmann, Hwang Jiwon, Van Nguyen, Vikas Satyananda, Jussuf T. Kaifi, Joshua Chan, Satyanarayana Rachagani. Red cabbage juice reprograms the gut microbiome and enhances butyrate production to prevent colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 3619.