Tissue Microbiome Profiling Identifies an Enrichment of Specific Enteric Bacteria in Opisthorchis viverrini Associated Cholangiocarcinoma.
Tissue Microbiome Profiling Identifies an Enrichment of Specific Enteric Bacteria in Opisthorchis viverrini Associated Cholangiocarcinoma.
复制标题
DOI：
10.1016/j.ebiom.2016.04.034
复制
发表时间：
2016-06
期刊：
影响因子：
11.1
通讯作者：
Nagarajan N
中科院分区：
文献类型：
--
作者：
Chng KR;Chan SH;Ng AHQ;Li C;Jusakul A;Bertrand D;Wilm A;Choo SP;Tan DMY;Lim KH;Soetinko R;Ong CK;Duda DG;Dima S;Popescu I;Wongkham C;Feng Z;Yeoh KG;Teh BT;Yongvanit P;Wongkham S;Bhudhisawasdi V;Khuntikeo N;Tan P;Pairojkul C;Ngeow J;Nagarajan N
胆管癌(CCA)是胆道系统的原发癌。胆管组织微生物群在CCA肿瘤发生中的作用尚未确定。为了解决这一问题，60例原发CCA肿瘤和配对的正常人，来自与肝吸虫(Opisthorchis Viverrini)相关的(Ova，n=328)和非O。Viverrini相关(非卵子，n=332)癌症，使用高通量16S rRNA测序进行分析。在胆管组织中观察到一种独特的、组织特异性的微生物群，主要由Dietziaceae、Pusomonadaceae和Oxalbacteraceae等细菌科占优势。在肿瘤和配对正常样本(与非癌症正常对照相比)的几个细菌家族中发现了微生物组的全身性扰动，区分肿瘤与配对正常对照的狭窄滋养单胞菌种类显著增加。寄生虫相关(OVA)组与非相关(非OVA)组的比较确定了特定肠道细菌(双歧杆菌科、肠杆菌科和肠球菌科)的浓缩。其中一个丰富的家族，双歧杆菌科，被发现在viverrini微生物群中占优势，为这种寄生虫提供了一种机械联系。对CCA微生物群的功能分析和比较表明，在卵子组织中产生胆汁酸和氨的潜力更大，将改变的微生物群与致癌联系起来。这些结果定义了驻留在胆管中的独特微生物群落、寄生虫感染和组织微环境如何相互影响，并促成癌症。与胆管感染有关的滋养细胞单胞菌在非吸虫相关性胆管癌的肿瘤组织中大量存在。鲜活奥氏菌感染可改变胆道组织微生物群组成。具有与致癌相关的代谢产物的肠道细菌富含与病原菌相关的组织微生物群。微生物区系与胃肠道(GI)癌之间的联系已被广泛研究。然而，组织微生物组在胆管癌(CCA)中所起的作用在很大程度上是未知的。在这项研究中，我们发现了肝吸虫相关和非相关CCA组织微生物群有趣的组成差异。综上所述，我们的数据表明寄生虫感染、组织微生物群变化、组织微环境变化和CCA发展之间存在联系。
Cholangiocarcinoma (CCA) is the primary cancer of the bile duct system. The role of bile duct tissue microbiomes in CCA tumorigenesis is unestablished. To address this, sixty primary CCA tumors and matched normals, from both liver fluke (Opisthorchis viverrini) associated (OVa, n = 28) and non-O. viverrini associated (non-OVa, n = 32) cancers, were profiled using high-throughput 16S rRNA sequencing. A distinct, tissue-specific microbiome dominated by the bacterial families Dietziaceae, Pseudomonadaceae and Oxalobacteraceae was observed in bile duct tissues. Systemic perturbation of the microbiome was noted in tumor and paired normal samples (vs non-cancer normals) for several bacterial families with a significant increase in Stenotrophomonas species distinguishing tumors vs paired normals. Comparison of parasite associated (OVa) vs non-associated (non-OVa) groups identified enrichment for specific enteric bacteria (Bifidobacteriaceae, Enterobacteriaceae and Enterococcaceae). One of the enriched families, Bifidobacteriaceae, was found to be dominant in the O. viverrini microbiome, providing a mechanistic link to the parasite. Functional analysis and comparison of CCA microbiomes revealed higher potential for producing bile acids and ammonia in OVa tissues, linking the altered microbiota to carcinogenesis. These results define how the unique microbial communities resident in the bile duct, parasitic infections and the tissue microenvironment can influence each other, and contribute to cancer. Stenotrophomonas, implicated in bile duct infections, is enriched in tumor tissues of non-fluke related cholangiocarcinoma. O. viverrini infection may alter composition of bile duct tissue microbiomes. Enteric bacteria with metabolic outputs linked to carcinogenesis are enriched in O. viverrini associated tissue microbiomes. The link between microbiota and cancer of the gastrointestinal (GI) tract has been extensively studied. However, the role of tissue microbiome in cholangiocarcinoma (CCA), cancer of the bile duct (an organ connected to the GI tract), is largely unknown. In this study, we detected intriguing compositional differences in the tissue microbiomes of liver fluke related and non-related CCA. Taken together, our data suggests a connection between parasitic infections, tissue microbiome alterations, tissue micro-environment changes and CCA development.