Gleeson Michael W
Department of Veterans Affairs Medical Center, White River Junction, VT, USA.
The Geisel School of Medicine at Dartmouth, Hanover, NH, USA.
Curr Treat Options Gastroenterol. 2019 Sep;17(3):378-393. doi: 10.1007/s11938-019-00241-6.
Liver disease, colon cancer, and the gut microbiome are intimately interrelated; however, the connections linking liver disease and colorectal neoplasia via the gut microbiota remain poorly understood and rarely addressed in a single space. The goal of this review is to take a broad perspective on the clinical problem of colorectal neoplasia in the liver disease population, recognize the significance of the clinical study findings, and delve into the evidence supporting putative molecular mechanisms connecting dysbiosis in the progression of liver disease to the development of colorectal neoplasia.
Clinical studies have recently reported increased risk of colorectal neoplasia in patients with fatty liver disease, and risk increases with liver disease severity. Concurrently, the evolution of -omics technology has shown dysregulation of the gut microbial community, termed dysbiosis, in the progression of liver disease. Specific microbes enriched in the gut flora of liver disease patients have been linked to colon cancer and adenomatous precursor lesions. The gut microbiome of liver disease patients generates a pro-neoplastic environment, mediated via altered bile acid signaling and a dysregulated inflammatory response that suppresses immune surveillance. Research focused on the mechanisms linking liver disease to colorectal neoplasia via the gut microbiome is needed to help us prepare for the rising tide of colon cancer in young patients with an increasing prevalence of liver disease.
肝脏疾病、结肠癌和肠道微生物群密切相关;然而,通过肠道微生物群将肝脏疾病与结直肠肿瘤联系起来的关联仍知之甚少,且很少在同一篇文章中进行探讨。本综述的目的是从广泛的角度审视肝病患者结直肠肿瘤的临床问题,认识临床研究结果的重要性,并深入研究支持将肝病进展过程中的微生物失调与结直肠肿瘤发生联系起来的假定分子机制的证据。
临床研究最近报告称,脂肪肝患者患结直肠肿瘤的风险增加,且风险随肝病严重程度而增加。与此同时,组学技术的发展表明,在肝病进展过程中,肠道微生物群落出现失调,即生态失调。肝病患者肠道菌群中富集的特定微生物与结肠癌和腺瘤性前体病变有关。肝病患者的肠道微生物群通过改变胆汁酸信号传导和失调的炎症反应介导产生促肿瘤环境,从而抑制免疫监视。需要开展专注于通过肠道微生物群将肝病与结直肠肿瘤联系起来的机制的研究,以帮助我们应对肝病患病率不断上升的年轻患者中结肠癌发病率上升的趋势。