Microbiome Signatures in a Fast- and Slow-Progressing Gastric Cancer Murine Model and Their Contribution to Gastric Carcinogenesis.
Microbiome Signatures in a Fast- and Slow-Progressing Gastric Cancer Murine Model and Their Contribution to Gastric Carcinogenesis.
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DOI：
10.3390/microorganisms9010189
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发表时间：
2021-01-17
期刊：
影响因子：
4.5
通讯作者：
Obonyo M
中科院分区：
文献类型：
--
作者：
Bali P;Coker J;Lozano-Pope I;Zengler K;Obonyo M
胃癌是世界上第三大常见的癌症死亡原因，而幽门螺杆菌（H。幽门螺杆菌）是导致胃癌的主要原因。除了幽门螺杆菌感染，整体胃微生物群最近已成为胃癌进展的潜在因素。以前我们已经确定，当感染H.猫因此，为了评估微生物群在这种快速进展的胃癌模型中的作用，我们研究了具有不同基因型背景的小鼠中胃微生物组的变化：野生型（WT），MyD 88缺陷型（Myd 88 −/−），Toll/白细胞介素-1受体（TIR）结构域缺陷的小鼠，含衔接子诱导的干扰素-β（TRIF，TrifLps 2）和MyD 88-和TRIF-缺陷（Myd 88-/-/TrifLps 2，双敲除（DKO））小鼠。我们比较了未感染和螺杆菌感染小鼠的α多样性、β多样性、相对丰度和相对丰度比的对数倍差的变化，并研究了它们与原位胃癌疾病进展的相关性。我们观察到感染H.所有基因型的猫。在所有感染小鼠中均观察到弯曲杆菌，Myd 88 −/−小鼠在3个月和6个月时丰度显著降低。与TrifLps 2和WT小鼠相比，在感染的Myd 88 −/−和DKO小鼠中，在3个月和6个月时观察到乳杆菌目的急剧增加，暗示这些细菌在胃癌进展中可能起作用。这一点在比较乳酸杆菌目对数倍数差异与组织学数据时得到进一步加强，表明乳酸杆菌目与螺杆菌感染和胃癌进展密切相关。我们的研究表明，基因型的差异可能会影响胃微生物组，并使其更容易在螺杆菌感染后发生胃癌。此外，乳酸杆菌的增加可能有助于胃癌的更快发展，并可能作为胃癌快速进展形式的潜在生物标志物。
Gastric cancer is the third most common cause of death from cancer in the world and infection with Helicobacter pylori (H. pylori) is the main cause of gastric cancer. In addition to Helicobacter infection, the overall stomach microbiota has recently emerged as a potential factor in gastric cancer progression. Previously we had established that mice deficient in myeloid differentiation primary response gene 88 (MyD88, Myd88−/−) rapidly progressed to neoplasia when infected with H. felis. Thus, in order to assess the role of the microbiota in this fast-progressing gastric cancer model we investigated changes of the gastric microbiome in mice with different genotypic backgrounds: wild type (WT), MyD88-deficient (Myd88−/−), mice deficient in the Toll/interleukin-1 receptor (TIR) domain-containing adaptor-inducing interferon-β (TRIF, TrifLps2), and MyD88- and TRIF-deficient (Myd88−/−/TrifLps2, double knockout (DKO)) mice. We compared changes in alpha diversity, beta diversity, relative abundance, and log-fold differential of relative abundance ratios in uninfected and Helicobacter infected mice and studied their correlations with disease progression to gastric cancer in situ. We observed 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. A sharp increase in Lactobacillales in infected Myd88−/− and DKO mice at 3 and 6 months was observed as compared to TrifLps2 and WT mice, hinting at a possible role of these bacteria in gastric cancer progression. This was further reinforced upon comparison of Lactobacillales log-fold differentials with histological data, indicating that Lactobacillales are closely associated with Helicobacter infection and gastric cancer progression. Our study suggests that differences in genotypes could influence the stomach microbiome and make it more susceptible to the development of gastric cancer upon Helicobacter infection. Additionally, increase in Lactobacillales could contribute to faster development of gastric cancer and might serve as a potential biomarker for the fast progressing form of gastric cancer.
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