关键词: FFAR2 IL-6/STAT3 SCFAs TNFAIP8 cancer onset machine learning oral microbiota

来  源:   DOI:10.3390/cancers15112898   PDF(Pubmed)

Abstract:
The association between oral microbiota and cancer development has been a topic of intense research in recent years, with compelling evidence suggesting that the oral microbiome may play a significant role in cancer initiation and progression. However, the causal connections between the two remain a subject of debate, and the underlying mechanisms are not fully understood. In this case-control study, we aimed to identify common oral microbiota associated with several cancer types and investigate the potential mechanisms that may trigger immune responses and initiate cancer upon cytokine secretion. Saliva and blood samples were collected from 309 adult cancer patients and 745 healthy controls to analyze the oral microbiome and the mechanisms involved in cancer initiation. Machine learning techniques revealed that six bacterial genera were associated with cancer. The abundance of Leuconostoc, Streptococcus, Abiotrophia, and Prevotella was reduced in the cancer group, while abundance of Haemophilus and Neisseria enhanced. G protein-coupled receptor kinase, H+-transporting ATPase, and futalosine hydrolase were found significantly enriched in the cancer group. Total short-chain fatty acid (SCFAs) concentrations and free fatty acid receptor 2 (FFAR2) expression levels were greater in the control group when compared with the cancer group, while serum tumor necrosis factor alpha induced protein 8 (TNFAIP8), interleukin-6 (IL6), and signal transducer and activator of transcription 3 (STAT3) levels were higher in the cancer group when compared with the control group. These results suggested that the alterations in the composition of oral microbiota can contribute to a reduction in SCFAs and FFAR2 expression that may initiate an inflammatory response through the upregulation of TNFAIP8 and the IL-6/STAT3 pathway, which could ultimately increase the risk of cancer onset.
摘要:
近年来,口腔微生物群与癌症发展之间的关联一直是研究的热点。有令人信服的证据表明口腔微生物组可能在癌症发生和进展中发挥重要作用。然而,两者之间的因果关系仍然是一个争论的话题,潜在的机制还没有完全理解。在这项病例对照研究中,我们的目的是确定与几种癌症类型相关的常见口腔微生物群,并研究可能引发免疫反应并在细胞因子分泌后引发癌症的潜在机制.从309名成年癌症患者和745名健康对照中收集唾液和血液样本,以分析口腔微生物组和癌症发生机制。机器学习技术揭示了六个细菌属与癌症有关。丰富的明串珠菌,链球菌,无性腺,普雷沃氏菌在癌症组中减少了,而嗜血杆菌和奈瑟菌的丰度增强。G蛋白偶联受体激酶,H+转运ATP酶,在癌症组中发现富腺苷水解酶显着富集。与癌症组相比,对照组的总短链脂肪酸(SCFA)浓度和游离脂肪酸受体2(FFAR2)表达水平更高,而血清肿瘤坏死因子α诱导蛋白8(TNFAIP8),白细胞介素-6(IL6),与对照组相比,癌症组的信号转导和转录激活因子3(STAT3)水平更高。这些结果表明,口腔微生物群组成的改变可以导致SCFA和FFAR2表达的减少,这可能通过TNFAIP8和IL-6/STAT3途径的上调引发炎症反应。这最终会增加癌症发病的风险。
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