Prognostic Role of Short-Chain Fatty Acid-Producing Gut Microbiota and Gut Microbial Dynamics in Patients with Hepatocellular Carcinoma Receiving Chemoembolization: A Prospective Study

Abstract

Purpose: Transarterial chemoembolization (TACE) may cause gut dysbiosis by increasing portal vein pressure. However, its association with clinical outcomes remains unknown. We hypothesized that gut microbiota composition and diversity are associated with treatment response and prognosis in patients with hepatocellular carcinoma (HCC) undergoing TACE. Patients and Methods: This single-center, prospective cohort study included 96 adult HCC patients treated with TACE from April 2021 to November 2023. Fecal samples were collected before TACE (P0), one day (P1), and one month (P2) after TACE. Fecal 16S rRNA taxonomy was analyzed to evaluate microbial diversity, composition, and dynamic changes at each time point. The primary outcome was the association between the initial response to TACE and changes in microbial diversity and composition. Results: Out of the total participants, 63 (65.6%) were responders and 33 (34.4%) were non-responders. Responder stool samples had higher alpha-diversity than those of non-responders at baseline (median Shannon index: 4.26 vs 4.09), albeit not reaching statistical significance, and a higher abundance of short-chain fatty acid (SCFA)-producing bacteria at all time points. Alpha-diversity significantly decreased one day after TACE (P < 0.05 for P1 vs P0) and tended to recover one month later in the responders, albeit without statistical significance for P2 vs P0. Regarding beta-diversity, there were some changes in both responders and non-responders during the post-TACE period, albeit with different patterns. A low abundance of Roseburia cecicola (HR, 3.44; 95% CI, 1.10- 10.8) and Dialister_uc (HR, 3.90; 95% CI, 1.32- 11.6; both P < 0.05) at baseline was associated with worse overall survival. Conclusion: Specific SCFA-producing bacteria, such as Roseburia cecicola and Dialister_uc, were associated with treatment response and survival after TACE in patients with HCC, suggesting a potential prognostic role of the gut microbiome.