Gastric cancer is the third most common cancer in the world and Helicobacter spp. being one of the main factors responsible for development of cancer. Alongside Helicobacter the microbiota of the stomach mucosa may also play an important role in gastric cancer progression. Previously we had established that MyD88 deficient mice rapidly progressed to neoplasia when infected with H. felis. Thus, in order to assess the role of microbiota in gastric cancer progression we measured the changes in microbial diversity of the stomach in mice with different genotypic backgrounds (Wild type (WT), MyD88 deficient (MyD88-/-), mice deficient in the Toll/IL-1R (TIR) domain-containing adaptor-inducing interferon-β (TRIF, Triflps2), and MyD88 and Trif deficient (MyD88-/- and Trif-/-)double knockout (DKO) mice), both in uninfected and Helicobacter infected mice and its correlation of these changes with gastric cancer progression. We observed that there was an overall reduction in microbial diversity post infection with H. felis across all genotypes. Campylobacterales were observed in all infected mice, with marked reduction in abundance at 3 and 6 months in MyD88-/- mice. This low abundance of H. pylori could facilitate dominance of other organisms of microbiome like Lactobacilliales. A sharp increase in Lactobacilliales in infected MyD88-/- and DKO mice at 3 and 6 months was observed as compared to Trif-/- and WT mice suggesting its possible role in gastric cancer progression. This was further reinforced upon comparison of Lactobacillus ratio with histological data suggesting that Lactobacillales is closely associated with Helicobacter infection and gastric cancer progression. Thus, this study firstly suggests that difference in genotypes could define the stomach microbiome and make it more susceptible to development of gastric cancer upon Helicobacter infections. Secondly the increase in Lactobacillales could contribute to faster development of gastric cancer and serve as a probable bio marker for fast progressing form of gastric cancer.

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快速和缓慢进展的胃癌小鼠模型中的微生物组特征及其对胃癌发生的作用

胃癌是世界上第三大最常见的癌症，幽门螺杆菌属。是导致癌症发展的主要因素之一。除幽门螺杆菌外，胃粘膜微生物群也可能在胃癌的进展中起重要作用。以前，我们已经确定MyD88缺陷小鼠在感染了H. felis后迅速发展为赘生物。因此，为了评估微生物群在胃癌进展中的作用，我们测量了具有不同基因型背景（野生型（WT），MyD88缺陷（MyD88-/-），小鼠缺乏胃癌）的小鼠胃微生物多样性的变化。包含Toll / IL-1R（TIR）域的衔接子诱导干扰素-β（TRIF，Triflps2）和MyD88和Trif缺陷型（MyD88-/-和Trif-/-）双敲除（DKO）小鼠），感染和未感染幽门螺杆菌的小鼠均如此，并且这些变化与胃癌进展的相关性。我们观察到，在所有基因型中，感染H. felis后的微生物多样性总体上下降了。在所有感染的小鼠中均观察到弯曲杆菌，在MyD88-/-小鼠中3和6个月时丰度明显降低。幽门螺杆菌的这种低丰度可以促进其他微生物组如乳杆菌的优势。与Trif-/-和WT小鼠相比，在感染的MyD88-/-和DKO小鼠中，在3个月和6个月时，乳杆菌的急剧增加，表明其可能在胃癌的进展中起作用。通过比较乳酸杆菌比率与组织学数据进一步证实了这一点，这表明乳酸杆菌与幽门螺杆菌感染和胃癌的进展密切相关。因此，这项研究首先表明基因型的差异可以定义胃微生物组，并使其更易于因幽门螺杆菌感染而发展为胃癌。其次，乳杆菌的增加可能有助于胃癌的更快发展，并可能是胃癌快速发展的可能的生物标志。