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• 将晚期结、直肠癌发生率降低到<10%
Metagenomics(宏基因组学)
ቤተ መጻሕፍቲ ባይዱ
• 通过直接从环境样品中提取全部微生 物的DNA,构建宏基因组文库,利用基 因组学的研究策略研究环境样品所包 含的全部微生物的遗传组成及其群落 功能。
• 肿瘤与无瘤对照组样本宏基因组分析对比,从结直肠癌( CRC)患者数量揭示肠道菌群与癌症之间有很强的关联。 这些菌群可对无创肿瘤筛查提供潜在的系统性研究。
A metagenomic classifier for CRC
Fig.1 Relative abundances of 22 gut microbial species, collectively associated with CRC, are displayed as heatmap in the left panel as fold change over the median relative abundance observed in controls(the control group included neoplasia‐free and small adenoma patients).
Thanks
潘咏絮 1401880
Potential of fecal microbiota for early‐stage detection of colorectal cancer
Georg Zeller [Germany]
Part 1 Abstract
• Several bacterial species have been implicated in the development of colorectal carcinoma (CRC), but CRC ‐ associated changes of fecal microbiota and their potential for cancer screening remain to be explored. Here, we used metagenomic sequencing of fecal samples to identify taxonomic markers that distinguished CRC patients from tumor‐free controls in a study population of 156 participants. Accuracy of metagenomic CRC detection was similar to the standard fecal occult blood test (FOBT) and when both approaches were combined, sensitivity improved > 45% relative to the FOBT, while maintaining its specificity. Accuracy of metagenomic CRC detection did not differ significantly between early‐ and late‐stage cancer and could be validated in independent patient and control populations (N = 335) from different countries. CRC ‐ associated changes in the fecal microbiome at least partially reflected microbial community composition at the tumor itself, indicating that observed gene pool differences may reveal tumor‐related host–microbe interactions. Indeed, we deduced a metabolic shift from fiber degradation in controls to utilization of host carbohydrates and amino acids in CRC patients, accompanied by an increase of lipopolysaccharide metabolism.
• Proteobacteria (变形菌)were significantly increased in CRC patients, whereas Actinobacteria (放线菌)were decreased。
• Bacteroidetes (拟杆菌) and Firmicutes (厚壁菌 )were enriched and depleted, respectively, in CRC patients。
The KEGG resource for deciphering the genome • KEGG:Kyoto Encyclopedia of Genes and Genomes(京都基因与基因组百科全书) • KEGG is a database resource for understanding high-level functions and utilities of the biological system • To distinguish by different color encoding
Potential influencing factors
• An enrichment of hemolysin transport, RTX toxin transport, and type II secretion systems in CRC metagenomes hints at an increase of pathogenicity processes encoded in the genomes of gram‐negative bacteria. • Fusobacterium adhesin(梭杆菌粘附素)
Part 2 Introduction
• methods
1.FOBT(fecal occult-blood test)
2.Metagenomics 3.FOBT+Metagenomics
FOBT
Fecal occult-blood test,即便潜血(便隐 血)检查,是用来检查粪便中隐匿的红细 胞或血红蛋白,转铁蛋白一项实验。是目 前标准的无创筛选检查。 Traditional method New method (accuracy,quick,efficient)
KEGG
CRC marker species in inflammatory bowel disease
宏基因组分类器的预测排名:真阴性(TN),假阳性(FP),假阴性(FN)和 真阳性(TP)
Potential influencing factors
(1)CRC‐associated microbiota for uptake and metabolism of some amino acids via the putrefaction pathway • ‘Oral microbiome hypothesis’: Fusobacterium 梭形杆菌属)might cause or contribute to tumorigenesis • Peptostreptococcus stomatis and Porphyromonas asaccharolytica, which we found to be associated with CRC, were also described as oral pathogens • putrescine/spermidine metabolism has been described as a core trait of the oral microbiota
Potential influencing factors
(2)most notably an increased potential for lipopolysaccharide (LPS) metabolism: consistent with a CRC‐associated expansion of gram‐negative bacteria that bear LPS antigens on their outer membranes LPS triggers an inflammatory signaling cascade, which in turn could promote inflammation‐induced carcinogenesis
Part 3 Results
1.The gut microbiome of a CRC study population 2.A metagenomic classifier for CRC 3.CRC marker species in inflammatory bowel disease
The gut microbiome of a CRC study population
四甲基联苯胺法(家用便隐血检测试纸)
• 原理:试纸上包被一层四甲基联苯胺显色染料和 过氧化物膜,在马桶或便池内,粪便中的血红蛋 白、血红素可扩散到周围的水中,血红蛋白中的 亚铁血红素有类似过氧化物酶的活性,能通过过 氧化物膜释放出氧,将无色的四甲基联苯胺氧化 成有色的联苯胺兰,呈蓝绿色显出(阳性)。