PDF(Pubmed)
Abstract：
Chronic inflammation of the colon (colitis) is a known risk factor for inflammatory-driven colorectal cancers (id-CRCs), and intestinal microbiota has been implicated in the etiology of id-CRCs. Manipulation of the microbiome is a clinically viable therapeutic approach to limiting id-CRCs. To understand the microbiome changes that occur over time in id-CRCs, we used a mouse model of id-CRCs with the treatment of azoxymethane (AOM) and dextran sodium sulfate (DSS) and measured the microbiome over time. We included cohorts where the microbiome was restored using cage bedding swapping and where the microbiome was depleted using antibiotics to compare to untreated animals. We identified consistent increases in Akkermansia in mice receiving horizontal microbiome transfer (HMT) via cage bedding swapping, while the control cohort had consistent longitudinal increases in Anaeroplasma and Alistipes. Additionally, fecal lipocalin-2 (Lcn-2), a marker of intestinal inflammation, was elevated in unrestored animals compared to restored and antibiotic-treated counterparts following HMT. These observations suggest a potential role for Akkermansia, Anaeroplasma, and Alistipes in regulating colonic inflammation in id-CRCs.
摘要：
结肠慢性炎症（结肠炎）是炎症驱动的结直肠癌（id-CRC）的已知危险因素，和肠道微生物群与id-CRC的病因有关。微生物组的操纵是限制id-CRC的临床可行的治疗方法。要了解ID-CRC中随时间发生的微生物组变化，我们使用了一个id-CRCs小鼠模型,用偶氮甲烷(AOM)和葡聚糖硫酸钠(DSS)处理,并随时间测量了微生物组.我们包括使用笼子垫层交换恢复微生物组的队列，以及使用抗生素耗尽微生物组的队列，以与未经治疗的动物进行比较。我们发现通过笼子垫层交换接受水平微生物组转移（HMT）的小鼠中Akkermansia的持续增加，而对照组有一致的纵向增加的厌氧虫和Alistpes。此外,粪便脂质运载蛋白-2（Lcn-2），肠道炎症的标志，与HMT后恢复和抗生素治疗的对应物相比，未恢复的动物中升高。这些观察表明Akkermansia的潜在作用，厌氧等离子体,和Alistipes在调节id-CRC结肠炎症中的作用。
