{
  "abstract": "Background Chemoresistance to 5-fluorouracil (5-FU) and oxaliplatin limits therapeutic success in colorectal cancer (CRC). Metagenomic profiling of CRC patients previously identified enrichment of butyrate-producing bacteria in chemotherapy responders, particularly Roseburia intestinalis (Ri). We investigated whether Ri enhances chemotherapy sensitivity in CRC and elucidated the underlying molecular mechanisms.Methods Conditioned media (CM) derived from Ri were applied to chemo-resistant CRC cell lines (HCT8/FU, HCT8/L, HCT116/FU, HCT116/L). Cell viability and apoptosis were assessed following treatment with 5-FU or oxaliplatin. Transcriptomic analysis and Western blotting were used to examine activation of MAPK–c-Jun N-terminal kinase (JNK) signalling pathways. In vivo efficacy was evaluated using azoxymethane–dextran sulfate sodium (AOM–DSS) CRC mice receiving oral Ri with intraperitoneal chemotherapy during the final three weeks, and xenograft models established with chemo-resistant HCT116 cells treated with Ri plus chemotherapy (5-FU 40 mg/kg; oxaliplatin 7.5 mg/kg). Tumour burden, tumour multiplicity, and apoptosis (TUNEL assay) were quantified.Results Ri CM significantly reduced the viability of chemo-resistant CRC cells ( IDDF2026-ABS-0173 Figure 1(A), P<0.01) and synergistically enhanced apoptosis when combined with 5-FU or oxaliplatin (IDDF2026-ABS-0173 Figure 1(B), P<0.0001). Metabolomic profiling identified butyrate as the predominant metabolite enriched in Ri CM and stool samples from chemotherapy responders. Mechanistically, Ri-derived metabolites activated MAPK–JNK signalling, resulting in increased cleavage of PARP and caspase-3/7 in resistant CRC cells. In AOM–DSS mice, Ri supplementation significantly enhanced chemotherapy efficacy, reducing tumour burden and tumour multiplicity in both oxaliplatin- and 5-FU-treated groups (P<0.05). In xenograft models, Ri markedly potentiated the antitumor effects of both chemotherapeutic agents, resulting in smaller tumour size and weight and higher apoptotic indices compared with chemotherapy alone (P<0.05).Conclusions Across complementary in vitro systems and two CRC mouse models, Roseburia intestinalis consistently enhanced chemotherapy response through activation of MAPK–JNK-mediated apoptosis and reversal of chemoresistance. These findings support Ri as a promising microbiome-based therapeutic candidate to augment standard CRC chemotherapy.Abstract IDDF2026-ABS-0173 Figure 1",
  "authors": [
    {
      "affiliations": [
        "Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore"
      ],
      "name": "Jason Xing Kang"
    },
    {
      "affiliations": [
        "Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore"
      ],
      "name": "Levene Wenqian Chua"
    },
    {
      "affiliations": [
        "Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore"
      ],
      "name": "Han Xiao"
    },
    {
      "affiliations": [
        "Institute of Digestive Disease, Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong"
      ],
      "name": "Tianhui Li"
    },
    {
      "affiliations": [
        "Institute of Digestive Disease, Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong"
      ],
      "name": "Kai Yuan"
    },
    {
      "affiliations": [
        "Institute of Digestive Disease, Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong"
      ],
      "name": "Jun Yu"
    },
    {
      "affiliations": [
        "Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore"
      ],
      "name": "Sunny Hei Wong"
    },
    {
      "affiliations": [
        "Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore"
      ],
      "name": "Joseph Jao-Yiu Sung"
    }
  ],
  "title": "IDDF2026-ABS-0173 Roseburia intestinalis enhances chemotherapy sensitivity in colorectal cancer through MAPK–JNK–mediated apoptosis",
  "uid": "9b6be297-1f8c-5021-a9f7-f118475e1318"
}