在胃癌发生的幽门螺杆菌INS-GAS小鼠模型中,限制性共生菌群的胃定植复制了不同肠道菌群对肿瘤病变的促进作用。

PubMed ID
发表日期 2014年Jan月

原始出处 肠子
Gut
作者 Lertpiriyapong  Kvin  Whary  Mark T  Muthupalani  Sureshkumar  Lofgren  Jennifer L  Gamazon  Eric R  Feng  Yan  Ge  Zhongming  Wang  Timothy C  Fox  James G 

文献标题 在胃癌发生的幽门螺杆菌INS-GAS小鼠模型中,限制性共生菌群的胃定植复制了不同肠道菌群对肿瘤病变的促进作用。
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.

文献摘要 OBJECTIVES

有肠道菌群的胃结肠癌(IF)已被证明促进幽门螺杆菌(Hp)相关的胃癌。然而,其机制是否涉及胃萎缩继发的特定或多样的微生物群的定植尚不清楚。

DESIGN

具有改变的Schaedler菌群(ASF)和幽门螺杆菌的胃结肠癌与无菌(GF)、幽门螺杆菌单相关(mHp)、限制性ASF(rASF;3种)和无特定病原体(复合IF)的病理学、免疫反应和促炎症和癌相关基因的mRNA表达相关,高胃泌素INS-GAS小鼠感染后7个月。

RESULTS

与rASFHp或IFHp联合克隆的雄性小鼠出现了最严重的病理变化。IFHp男性炎症反应最高,40%发生侵袭性胃肠道上皮内瘤变(GIN)。值得注意的是,rASFHp在男性中的定植率最高,23%的患者出现侵袭性GIN,炎症生物标志物表达升高。女性的病变较轻,没有出现GIN。雄性rASFHp小鼠的胃炎伴有梭状芽胞杆菌ASF356和类杆菌ASF519定植减少和鼠乳杆菌ASF361过度生长,支持炎症驱动的萎缩改变胃肠道共生体的胃生态位。幽门螺杆菌定植还提高了IL-11和癌症相关基因Ptger4和Tgf-β的表达,进一步支持幽门螺杆菌感染加速INS-GAS小鼠胃癌的发展。

CONCLUSIONS

rASFHp在雄性的GIN发育中是足够的,雌性的GIN发病率较低与较低的炎症反应、胃共生和Hp定植有关。共生体的定植效率似乎比微生物多样性更重要,并降低了特定胃肠道病原体导致癌症风险的可能性。


OBJECTIVES

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.

DESIGN

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.

RESULTS

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.

CONCLUSIONS

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.


获取全文 10.1136/gutjnl-2013-305178