Effects of High-Fiber Diet on Gut Microbiota, Metabolism, and Immune Microenvironment in Solid Tumor Patients: A Clinical Study
Cancer remains a major global public-health challenge and a central focus of medical research. According to the International Agency for Research on Cancer (IARC, 2020), 19.29 million new malignant tumors and 9.96 million cancer deaths occurred worldwide, \>90 % being solid cancers. Lung cancer alone accounted for 2.2 million new cases and 1.8 million deaths; \>75 % of patients were already at an advanced stage at diagnosis. Current options for late-stage solid tumors are limited: surgery is often impossible because of metastasis; cytotoxic chemotherapy produces dose-limiting toxicities (grade Ⅲ-Ⅳ myelosuppression 15-40 %, mucositis 50-80 %); radiotherapy risks pneumonitis (5-15 %) or enteritis (5-20 %) when tumors abut vital organs; targeted agents succumb to acquired resistance after a median 9-13 months; and immune-checkpoint inhibitors achieve \<40 % objective response with 7-15 % grade 3-4 immune-related adverse events. Dietary intervention is therefore emerging as a promising adjunct. Dietary fibre protects against cardiovascular and metabolic diseases, yet intake is universally low. WHO and the Chinese Nutrition Society recommend 25-30 g total fibre per day (≈15-21 g insoluble), whereas Chinese adults consume only \ 11 g insoluble fibre. High-fibre diets reshape gut microbiota, augment short-chain fatty acid (SCFA) production, strengthen intestinal barrier function, activate CD8⁺ T cells and dampen regulatory T cells, thereby enhancing anti-tumour immunity. A melanoma cohort showed improved progression-free survival under immunotherapy when fibre intake was high. Similar microbiota-immune axes may operate in colorectal and other solid cancers, but clinical data are scarce. We therefore propose a study to examine whether a high-insoluble-fibre diet (\>21 g/day) modulates gut-microbiota composition, metabolite profiles and peripheral-blood immune subsets in solid-tumour patients, and to evaluate consequent effects on treatment response and quality of life. The findings will clarify whether fibre-driven microbiota-immune crosstalk can be harnessed as a personalised nutritional strategy to improve cancer outcomes.
• (1) Sign a written informed consent form before any study - related procedures are carried out.
• (2) Males or females, aged 18 - 80 years old. (3) Diagnosed with solid tumors by pathological tissue biopsy. (4) According to the RECIST v1.1 (Response Evaluation Criteria in Solid Tumors Version 1.1) criteria, there is at least 1 measurable lesion (lesions previously treated with local therapies such as radiotherapy cannot be regarded as measurable lesions).
• (5) ECOG (Eastern Cooperative Oncology Group Performance Status) score of 0 - 1.
• (6) NRS - 2002 (Nutritional Risk Screening 2002) score \< 3. (7) BMI (Body Mass Index) ≥ 18.5 (can be adjusted appropriately according to the actual situation).
• (8) Patients who can eat orally or through a feeding tube and can tolerate enteral nutrition.
• (9) Sufficient organ function, and the subjects need to meet the following laboratory indicators: In the absence of granulocyte - colony - stimulating factor use in the past 14 days, the absolute neutrophil count ≥ 1.5×10⁹/L.
⁃ Platelets ≥ 75×10⁹/L. In the absence of blood transfusion or erythropoietin use in the past 7 days, hemoglobin ≥ 8 g/dL.
⁃ Serum albumin ≥ 3.0 g/dL. Total bilirubin ≤ 1.5× the upper limit of normal (ULN). Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤ 2.5×ULN. In case of liver metastasis, ALT and/or AST ≤ 5×ULN, and total bilirubin ≤ 3×ULN. In case of liver or bone metastasis, Alkaline Phosphatase (AKP) ≤ 5×ULN.
⁃ Creatinine clearance rate ≥ 50 mL/min (calculated according to the Cockcroft - Gault formula) or serum creatinine ≤ 1.5×ULN.
⁃ International Normalized Ratio (INR) ≤ 1.5×ULN, Prothrombin Time (PT) and Activated Partial Thromboplastin Time (APTT) ≤ 1.5×ULN.
⁃ Urine protein \< 2+ (if urine protein ≥ 2+, a 24 - hour urine protein quantification can be performed, and subjects with a 24 - hour urine protein quantification \< 2.0 g can be enrolled).
⁃ (10) Women of child - bearing potential must agree to avoid sexual intercourse (heterosexual intercourse) or use a reliable and effective contraceptive method from the signing of the informed consent form until at least 6 months after the last administration of the study drug. In addition, the serum HCG (Human Chorionic Gonadotropin) test must be negative within 3 days before the start of the study treatment, and the subject must be non - lactating. A female patient is considered to be of child - bearing potential if she is post - menopausal but has not reached the post - menopausal state (non - menstrual period ≥ 12 consecutive months, and no other causes are found except menopause) and has not undergone sterilization surgery (such as hysterectomy, bilateral tubal ligation, or bilateral oophorectomy).
⁃ (11) If there is a risk of pregnancy, all subjects (regardless of male or female) need to use a contraceptive method with an annual failure rate of less than 1% throughout the treatment period until 120 days after the last administration of the study drug (or 180 days after the last administration of the chemotherapy drug)