Dietary intervention reshapes gut microbiota and lipid metabolism to enhance anti-tumor immunity and prognosis in hepatocellular carcinoma: a randomized controlled trial

BACKGROUND: The gut microbiota is increasingly recognized as a key modulator of cancer pathogenesis and treatment response. We aimed to investigate the efficacy of a targeted dietary intervention on clinical outcomes, gut microbiota, lipid metabolism, and systemic immunity in patients with hepatocellular carcinoma (HCC). METHODS: In this single-center, prospective, randomized controlled trial, 100 patients with primary HCC were enrolled and randomly assigned (1:1) to an experimental group (n = 50), receiving a structured dietary intervention including probiotics, prebiotics, and specific dietary advice, or a control group (n = 50), receiving routine dietary care. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Secondary endpoints included changes in gut microbiota composition (16S rRNA sequencing), serum lipid profiles, immune cell subsets (flow cytometry), and quality of life (WHOQOL-100). RESULTS: After a median follow-up of 12 months, the experimental group showed significantly longer median PFS (9.4 vs. 7.3 months; Hazard Ratio [HR] = 0.52, 95% CI: 0.34–0.79, P < 0.01) and median OS (27.7 vs. 22.6 months; HR = 0.61, 95% CI: 0.42–0.88, P = 0.008). The intervention significantly increased microbial α-diversity and enriched beneficial genera such as Bifidobacterium and Lactobacillus. This was accompanied by improved lipid metabolism (reduced serum cholesterol and triglycerides) and a shift towards an anti-tumor immune profile, including increased CD8 + T cells and decreased regulatory T cells (Tregs). Quality of life scores were also significantly higher in the experimental group (P < 0.001). CONCLUSION: A targeted dietary intervention effectively modulates the gut microbiota, lipid metabolism, and systemic immunity in HCC patients, translating into significant improvements in survival and quality of life. These findings support microbiota-targeted dietary therapy as a promising adjunctive strategy in HCC management. TRIAL REGISTRATION: This study was registered with ClinicalTrials.gov (Identifier: NCT07143955; date: 19/08/2025).