Efficacy, Safety and Gut Microbiome Characteristics of Fecal Microbiota Transplantation and immunotherapy for Lung Cancer with Brain Metastases

Abstract Objective The blood-brain barrier (BBB) and central immunosuppressive microenvironment impair the efficacy of immunotherapy in lung-cancer patients with brain metastases (LCBM). Fecal microbiota transplantation (FMT) remodels intestinal microecology to regulate central immunity via the gut-brain axis. This study aimed to explore the collaboration of FMT and immunotherapy in LCBM, and the potential mechanism by which FMT reshapes gut microbiota to improve intracranial therapeutic efficacy. Methods Patients with LCBM who received FMT and immunotherapy at Changzhou Second People’s Hospital between May 2024 and April 2026 were enrolled in this retrospective study. Intracranial and extracranial lesion responses were assessed according to RECIST version 1.1. Survival analysis was conducted using the Kaplan-Meier method, and safety was evaluated based on CTCAE version 5.0. Fecal metagenomic sequencing was performed for one representative patient with prominent clinical benefit to characterize shifts in gut-microbiota composition and function before and after FMT. Results The final follow-up date was August, 2026, with a median follow-up of 10.5 months. The median age of enrolled 16 patients was 68 years (range 49–81 years); 68.75% (11/16) were male. Adenocarcinoma accounted for 93.75% (15/16). 56.25% (9/16) of patients had an ECOG-PS score ≥ 2. 75% (12/16) received one FMT session, and 50% (8/16) were treated in third-line or later settings. The intracranial objective response rate (ORR) was 37.5% and disease control rate (DCR) was 100%, with a median intracranial progression-free survival (iPFS) of 6.1 months. The extracranial ORR was 25.0% and DCR was 93.75%, with a median extracranial progression-free survival (ePFS) of 7.2 months. No significant efficacy difference was observed between patients with EGFR-TKI resistance and those without EGFR mutations. Most FMT-related adverse events were grade 1–2 self-limiting gastrointestinal reactions. Microbiota analysis of the beneficiary patient revealed severe baseline gut dysbiosis characterized by over-enrichment of Firmicutes and near-depletion of Bacteroidetes. After FMT, microbial diversity was restored and elevated; the Firmicutes/Bacteroidetes ratio reached a balanced status. Phocaeicola , Bacteroides and butyrate-producing beneficial bacteria were markedly enriched while pathogenic bacteria were effectively suppressed, accompanied by substantial improvement in anti-tumor metabolic capacity of the gut microbiome. Conclusion FMT is safe and feasible for patients with LCBM. By remodeling intestinal microecological balance, FMT achieves promising and durable intracranial disease control when combined with immonotherapy.