Gastric colonisation with a restricted commensal microbiota replicates the promotion of neoplastic lesions by diverse intestinal microbiota in the Helicobacter pylori INS-GAS mouse model of gastric carcinogenesis.
Gastric colonisation with a restricted commensal microbiota replicates the promotion of neoplastic lesions by diverse intestinal microbiota in the Helicobacter pylori INS-GAS mouse model of gastric carcinogenesis.
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DOI：
10.1136/gutjnl-2013-305178
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发表时间：
2014-01
期刊：
影响因子：
24.5
通讯作者：
Fox JG
中科院分区：
文献类型：
--
作者：
Lertpiriyapong K;Whary MT;Muthupalani S;Lofgren JL;Gamazon ER;Feng Y;Ge Z;Wang TC;Fox JG
肠道菌群 (IF) 的胃定植已被证明会促进幽门螺杆菌 (Hp) 相关的胃癌。然而，尚不清楚该机制是否涉及继发于胃萎缩的特定或多样化微生物群的定植。在感染后 7 个月的无菌 (GF)、Hp 单相关 (mHp)、限制性 ASF (rASF；3 个物种) 和无特定病原体 (复合 IF)、高胃泌素血症 INS-GAS 小鼠中，改变谢德勒菌群 (ASF) 和 Hp 的胃定植与病理、免疫反应以及促炎和癌症相关基因的 mRNA 表达相关。与 rASFHp 或 IFHp 共存的雄性小鼠出现最严重的病理。 IFHp 男性的炎症反应最高，40% 的人发展为侵袭性胃肠道上皮内瘤变 (GIN)。值得注意的是，rASFHp 定植在男性中最高，23% 的人发展为侵袭性 GIN，且炎症生物标志物的表达升高。女性的病变不太严重，没有人出现 GIN。雄性 rASFHp 小鼠的胃炎伴随着梭菌属 ASF356 和拟杆菌属 ASF519 定植的减少以及鼠乳杆菌 ASF361 的过度生长，这支持炎症驱动的萎缩改变了胃肠道共生菌的胃生态位。 Hp 定植还提高了 IL-11 和癌症相关基因 Ptger4 和 Tgf-β 的表达，进一步支持 Hp 感染加速 INS-GAS 小鼠胃癌的发展。 rASFHp 定植足以促进男性 GIN 的发育，而女性 GIN 发生率较低与较低的炎症反应以及胃共生和 Hp 定植有关。共生体的定殖效率似乎比微生物多样性更重要，并且降低了特定胃肠道病原体导致癌症风险的可能性。
Gastric colonisation with intestinal flora (IF) has been shown to promote Helicobacter pylori (Hp)-associated gastric cancer. However, it is unknown if the mechanism involves colonisation with specific or diverse microbiota secondary to gastric atrophy. Gastric colonisation with Altered Schaedler’s flora (ASF) and Hp were correlated with pathology, immune responses and mRNA expression for proinflammatory and cancer-related genes in germ-free (GF), Hp monoassociated (mHp), restricted ASF (rASF; 3 species), and specific pathogen-free (complex IF), hypergastrinemic INS-GAS mice 7 months postinfection. Male mice cocolonised with rASFHp or IFHp developed the most severe pathology. IFHp males had the highest inflammatory responses, and 40% developed invasive gastrointestinal intraepithelial neoplasia (GIN). Notably, rASFHp colonisation was highest in males and 23% developed invasive GIN with elevated expression of inflammatory biomarkers. Lesions were less severe in females and none developed GIN. Gastritis in male rASFHp mice was accompanied by decreased Clostridum species ASF356 and Bacteroides species ASF519 colonisation and an overgrowth of Lactobacillus murinus ASF361, supporting that inflammation-driven atrophy alters the gastric niche for GI commensals. Hp colonisation also elevated expression of IL-11 and cancer-related genes, Ptger4 and Tgf-β, further supporting that Hp infection accelerates gastric cancer development in INS-GAS mice. rASFHp colonisation was sufficient for GIN development in males, and lower GIN incidence in females was associated with lower inflammatory responses and gastric commensal and Hp colonisation. Colonisation efficiency of commensals appears more important than microbial diversity and lessens the probability that specific gastrointestinal pathogens are contributing to cancer risk.
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影响因子：
3.1
作者：
Rolig, Annah S.;Cech, Cynthia;Ottemann, Karen M.
通讯作者：
Ottemann, Karen M.
影响因子：
56.9
作者：
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通讯作者：
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影响因子：
24.5
作者：
Howlett M;Chalinor HV;Buzzelli JN;Nguyen N;van Driel IR;Bell KM;Fox JG;Dimitriadis E;Menheniott TR;Giraud AS;Judd LM
通讯作者：
Judd LM
影响因子：
2.3
作者：
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通讯作者：
Krejs, Guenter J.
影响因子：
4.7
作者：
Ohtani, Masahiro;Garcia, Alexis;Fox, James G.
通讯作者：
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