Schulz Christian, Vilchez-Vargas Ramiro, Öcal Elif, Koch Nadine, Puhr-Westerheide Daniel, Burnell Lu Fornés, Hirner-Eppeneder Heidrun, Benckert Julia, Pech Maciej, Reimer Peter, Verslype Chris, Kuhl Christiane, Tran Albert, Ricke Jens, Malfertheiner Peter, Alunni-Fabbroni Marianna
Department of Medicine II, LMU University Hospital, LMU Munich, Munich, Germany.
Department of Radiology, LMU University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany.
Gut Pathog. 2025 Jul 10;17(1):53. doi: 10.1186/s13099-025-00727-y.
Tumor tissues have been shown to host a diverse array of bacteria, suggesting a link between the intratumoral microbiota and the development and progression of cancer. The aim of this explorative study was to perform microbiome analysis in liver tumor and to evaluate its relationship with cancer stage and survival outcome.
We conducted an exploratory study on a cohort of 20 hepatocellular cancer patients from the SORAMIC trial. Patients were divided into curative and palliative groups according to treatment type (local ablation, alone or combined with systemic therapy). The V1-V2 regions of 16 S rRNA were sequenced starting from archival tissues. Amplicon Sequence Variants (ASVs) were taxonomically assigned to the upper (UGI) or lower (LGI) gastrointestinal tract. Bacteria were identified in both tumoral and non-tumoral tissues, showing higher diversity and correlation between diversity and shorter survival in the palliative group (S. aureus p < 0.05; B. parvula p < 0.01; A. chinensis p < 0.01). Both therapy groups were enriched with the genus Bacilli, including Streptococcus spp., Gemella haemolysans and Helicobacter pylori, commonly found in UGI. The results suggested that among palliative patients and those with shorter survival, G. haemolysans was more prevalent, while H. pylori was more often found in curative patients with longer survival. However none of the results were significantly different (p > 0.05). A higher microbiome biodiversity was associated with an increased number of lesions (Hoylesella, Agathobacter, Sphingobium, Cardiobacterium, Photobacterium and Serratia, all with p < 0.01).
The presence of bacteria, predominantly from communities of the UGI, suggests their translocation into liver tissue due to impaired barrier function of the upper gut or the ascending pathway along the biliary duct system. The intratumoral prevalence of bacteria with proinflammatory and oncogenic potential suggests their potential role in HCC pathomechanisms.
肿瘤组织已被证明含有多种细菌，这表明肿瘤内微生物群与癌症的发生和发展之间存在联系。本探索性研究的目的是对肝肿瘤进行微生物组分析，并评估其与癌症分期和生存结果的关系。
我们对来自SORAMIC试验的20例肝细胞癌患者队列进行了一项探索性研究。根据治疗类型（局部消融，单独或联合全身治疗）将患者分为治愈组和姑息组。从存档组织开始对16S rRNA的V1-V2区域进行测序。扩增子序列变体（ASV）在分类学上被归类为上胃肠道（UGI）或下胃肠道（LGI）。在肿瘤组织和非肿瘤组织中均鉴定出细菌，在姑息组中显示出更高的多样性以及多样性与较短生存期之间的相关性（金黄色葡萄球菌p<0.05；细小杆菌p<0.01；中华根瘤菌p<0.01）。两个治疗组均富含芽孢杆菌属，包括常见于上胃肠道的链球菌属、溶血孪生球菌和幽门螺杆菌。结果表明，在姑息患者和生存期较短的患者中，溶血孪生球菌更为普遍，而幽门螺杆菌更常见于生存期较长的治愈患者中。然而，所有结果均无显著差异（p>0.05）。较高的微生物组生物多样性与病变数量增加相关（霍耶斯氏菌属、阿加托杆菌属、鞘氨醇单胞菌属、心杆菌属、发光杆菌属和沙雷氏菌属，均p<0.01）。
细菌的存在，主要来自上胃肠道群落，表明它们由于上消化道屏障功能受损或沿胆管系统的上行途径而转移到肝组织中。具有促炎和致癌潜力的细菌在肿瘤内的流行表明它们在肝癌发病机制中的潜在作用。
