Structure of the gut microbiome following colonization with human feces determines colonic tumor burden.
Structure of the gut microbiome following colonization with human feces determines colonic tumor burden.
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人类粪便定植后肠道微生物组的结构决定了结肠肿瘤负担。
DOI：
10.1186/2049-2618-2-20
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发表时间：
2014
期刊：
影响因子：
15.5
通讯作者：
Schloss PD
中科院分区：
文献类型：
--
作者：
Baxter NT;Zackular JP;Chen GY;Schloss PD
越来越多的证据表明，肠道微生物群在结直肠癌（CRC）的发展中起着重要作用。结直肠癌患者的肠道微生物群在结构上与健康个体不同；然而，由于无法在疾病进展过程中跟踪个体，因此不可能在肿瘤发生过程中观察微生物组的变化。小鼠模型表明，这些变化可以进一步促进结肠肿瘤的发生。然而，这些模型依赖于小鼠适应的细菌种群，因此尚不清楚哪种人类适应的细菌种群负责调节肿瘤发生。我们将3名结直肠癌患者和3名健康人的粪便微生物群移植到无菌小鼠中，得到了6个结构不同的微生物群落。将这些小鼠置于化学诱导的结直肠癌模型中，小鼠之间的肿瘤发生程度不同。肿瘤数量的差异与小鼠的基线微生物组结构密切相关，但与人类供体的癌症状态无关。通过Dirichlet多项混合模型将基线群落划分为肠型，得到三种与肿瘤负荷相对应的肠型。与肿瘤负荷增加最显著正相关的类群是拟杆菌属、拟杆菌属、拟杆菌属和Akkermansia，它们均为革兰氏阴性。革兰氏阳性Clostridiales的成员，包括Clostridium Group XIVa的多个成员，与肿瘤呈强负相关。对每个群落宏基因组的推断分析显示，肿瘤数量与丁酸盐生产潜力呈负相关，肿瘤数量与宿主多糖降解能力呈正相关。尽管拥有不同的肠道群落，但所有小鼠在模型过程中都经历了保守的结构变化。这些变化的程度也与肿瘤发病率相关。我们的研究结果表明，微生物组的初始结构决定了结肠肿瘤发生的易感性。某些革兰氏阴性菌（拟杆菌属和Verrucomicrobia）和革兰氏阳性菌（梭菌属）在肿瘤易感性中似乎具有相反的作用。因此，群落结构的影响可能是由保护性、产生丁酸酯的种群和炎症性、降解黏液的种群之间的平衡所介导的。
A growing body of evidence indicates that the gut microbiome plays a role in the development of colorectal cancer (CRC). Patients with CRC harbor gut microbiomes that are structurally distinct from those of healthy individuals; however, without the ability to track individuals during disease progression, it has not been possible to observe changes in the microbiome over the course of tumorigenesis. Mouse models have demonstrated that these changes can further promote colonic tumorigenesis. However, these models have relied upon mouse-adapted bacterial populations and so it remains unclear which human-adapted bacterial populations are responsible for modulating tumorigenesis. We transplanted fecal microbiota from three CRC patients and three healthy individuals into germ-free mice, resulting in six structurally distinct microbial communities. Subjecting these mice to a chemically induced model of CRC resulted in different levels of tumorigenesis between mice. Differences in the number of tumors were strongly associated with the baseline microbiome structure in mice, but not with the cancer status of the human donors. Partitioning of baseline communities into enterotypes by Dirichlet multinomial mixture modeling resulted in three enterotypes that corresponded with tumor burden. The taxa most strongly positively correlated with increased tumor burden were members of the Bacteroides, Parabacteroides, Alistipes, and Akkermansia, all of which are Gram-negative. Members of the Gram-positive Clostridiales, including multiple members of Clostridium Group XIVa, were strongly negatively correlated with tumors. Analysis of the inferred metagenome of each community revealed a negative correlation between tumor count and the potential for butyrate production, and a positive correlation between tumor count and the capacity for host glycan degradation. Despite harboring distinct gut communities, all mice underwent conserved structural changes over the course of the model. The extent of these changes was also correlated with tumor incidence. Our results suggest that the initial structure of the microbiome determines susceptibility to colonic tumorigenesis. There appear to be opposing roles for certain Gram-negative (Bacteroidales and Verrucomicrobia) and Gram-positive (Clostridiales) bacteria in tumor susceptibility. Thus, the impact of community structure is potentially mediated by the balance between protective, butyrate-producing populations and inflammatory, mucin-degrading populations.
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影响因子：
30.3
作者：
Martens EC;Chiang HC;Gordon JI
通讯作者：
Gordon JI
影响因子：
3.7
作者：
Chen W;Liu F;Ling Z;Tong X;Xiang C
通讯作者：
Xiang C
影响因子：
14.9
作者：
Pruesse E;Quast C;Knittel K;Fuchs BM;Ludwig W;Peplies J;Glöckner FO
通讯作者：
Glöckner FO
影响因子：
64.5
作者：
Chung H;Pamp SJ;Hill JA;Surana NK;Edelman SM;Troy EB;Reading NC;Villablanca EJ;Wang S;Mora JR;Umesaki Y;Mathis D;Benoist C;Relman DA;Kasper DL
通讯作者：
Kasper DL
DOI：
10.1126/science.1224820
发表时间：
2012-10-05
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Arthur JC;Perez-Chanona E;Mühlbauer M;Tomkovich S;Uronis JM;Fan TJ;Campbell BJ;Abujamel T;Dogan B;Rogers AB;Rhodes JM;Stintzi A;Simpson KW;Hansen JJ;Keku TO;Fodor AA;Jobin C
通讯作者：
Jobin C