The impact of intratumoral microbiota on lung adenocarcinoma progression

Background: Lung adenocarcinoma (LADC) is the most common lung cancer subtype. Intratumoral microbiota may affect tumour behaviour, but its role in LADC remains unclear. This study aimed to analyze the microbial characteristics of patients with lung adenocarcinoma at different stages and explore the impact of microbiota on the progression of lung adenocarcinoma, thereby providing novel insights for the diagnosis and treatment of lung adenocarcinoma. Methods: Patients diagnosed with lung adenocarcinoma through postoperative pathological examination at West China Hospital between 2019 and 2023 were included. Samples from precursor glandular lesions (PGL), adenocarcinoma (ADC) and paired normal lung (N) underwent 16S rRNA sequencing. Differential taxa were identified by LEfSe. Faecalibacterium prausnitzii (Fp) was validated using FISH and immunohistochemistry, and its effects were assessed by in-vitro assays and subcutaneous xenograft models. Results: PGL, ADC and N showed distinct microbial compositions, while alpha and beta diversity did not differ. LEfSe identified Faecalibacterium enriched in ADC group. Fp was a key discriminatory taxon. In vitro and in vivo, Fp enhanced LADC malignant phenotypes and tumour growth. Conclusions: Intratumoral microbiota varies with LADC invasiveness. Fp is enriched in invasive ADC and may promote LADC progression, highlighting a potential diagnostic and therapeutic target. erj;68/suppl_70/PA2953/F1 F1 F1

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