槟榔/槟榔(AN/BQ)咀嚼,太平洋和亚洲部分地区的普遍做法,是口腔和食道癌的独立原因,可能与肝癌有关。AN/BQ相关癌变的机制尚不清楚。在关岛人口中,我们先前证明AN/BQ咀嚼改变口腔细菌微生物组,包括口腔癌前病变的咀嚼者.特定分类群的富集,包括蓝细菌,被观察到。
我们进行了一项调查,以评估Areca儿茶和/或Piper槟榔植物作为关岛AN/BQ咀嚼物中蓝细菌和氰毒素的潜在来源。
我们用IlluminaMiSeq在122个口腔样品和30个槟榔和胡椒叶样品中评估了细菌16SrRNA。使用NCBI数据库查询蓝细菌序列以鉴定候选物种,并使用AntiSMASH5.0评估其参考序列的次生代谢物毒素。通过ELISA在来自30个植物样品的提取物和25个唾液样品的子集中测量所选择的毒素。
蓝细菌是槟榔和Piper槟榔植物中的主要类群,包含75%的序列。在口腔样品中检测到的蓝细菌含量较低,但在当前的AN/BQ咀嚼物中比以前/从未咀嚼的高90倍(p=0.001)。在唾液(25个样品中的15个)和Piper槟榔叶(10个样品中的6个)中检测到微囊藻毒素/结节素。在所有唾液和叶样品以及10个坚果/果壳中的7个中检测到圆柱精氨素。在槟榔的当前咀嚼物中,唾液中的圆柱精氨素水平显着升高(即,与仅咀嚼槟榔相比,切碎的槟榔坚果包裹在Piper槟榔叶中)。在唾液中检测到Anabaenopeptin(25个样本中有10个),所有叶子样本,和10个坚果/果壳中的7个。唾液anabaenopeptin浓度较弱,尽管意义重大,与口腔蓝藻相对丰度相关。
我们的研究表明,蓝细菌可以污染AN/BQ植物,并使咀嚼者暴露于有效的肝毒素。随着全球范围内与气候相关的蓝细菌过度生长的增加,我们的研究结果对人群的癌症风险具有广泛的意义.
Areca nut/betel quid (AN/BQ) chewing, a prevalent practice in parts of the Pacific and Asia, is an independent cause of cancers of the oral cavity and esophagus and may be linked to liver cancer. The mechanisms of AN/BQ-associated carcinogenesis are unclear. In a Guam population, we previously demonstrated that AN/BQ chewing alters the oral bacterial microbiome including in chewers with oral premalignant lesions. Enrichment of specific taxa, including Cyanobacteria, was observed.
We undertook an investigation to evaluate Areca catechu and/or Piper betle plants as potential sources of Cyanobacteria and cyanotoxins in AN/BQ chewers in Guam.
We evaluated bacterial 16S rRNA with Illumina MiSeq in 122 oral samples and 30 Areca catechu nut and Piper betle leaf samples. Cyanobacteria sequences were interrogated using the NCBI database to identify candidate species and their reference sequences were evaluated for secondary metabolite toxins using AntiSMASH 5.0. Selected toxins were measured by ELISA in extracts from 30 plant samples and in a subset of 25 saliva samples.
Cyanobacteria was the predominant taxa in Areca catechu and Piper betle plants, comprising 75% of sequences. Cyanobacteria was detected at low levels in oral samples but 90-fold higher in current AN/BQ chewers compared to former/never chewers (p = 0.001). Microcystin/
nodularin was detected in saliva (15 of 25 samples) and Piper betle leaves (6 of 10 samples). Cylindrospermopsin was detected in all saliva and leaf samples and 7 of 10 nut/husks. Salivary cylindrospermopsin levels were significantly higher in current chewers of betel quid (i.e., crushed Areca catechu nut wrapped in Piper betle leaf) compared to those chewing Areca nut alone. Anabaenopeptin was detected in saliva (10 of 25 samples), all leaf samples, and 7 of 10 nut/husks. Salivary anabaenopeptin concentration was weakly, albeit significantly, correlated with oral Cyanobacteria relative abundance.
Our study demonstrates that Cyanobacteria can contaminate AN/BQ plants and expose chewers to potent hepatotoxins. With worldwide increases in climate-related overgrowth of Cyanobacteria, our findings have broad implications for cancer risk across populations.