肠道菌群:对结直肠肿瘤有何影响
于君
时长:23:28 分会场:2019中国肠道大会 - 开幕式
Cancer is a major disease burden globally. The gut microbiome and its role in carcinogenesis is a rapidly evolving research field (Nat Biotechnol 2015). Mounting evidence has suggested that the gut microbiota is implicated in a variety of cancers especially in the colorectal cancer (CRC). In this connection, detailed and holistic investigations into the gut metagenome in CRC initiation, progression, and response to therapies are imperative. With our work in metagenomic profiling in CRC, we was the first to reveal an interacting oral pathogen network in CRC in Chinese (Nat Commun 2015, Gut 2017a) and among different populations (Microbiome 2018). We were first to demonstrate a causative role of gut microbiota in CRC development, which revealed that faecal transplantation of samples from patients with colorectal cancer promotes intestinal carcinogenesis in germ-free and conventional mice (Gastroenterology 2017a). Our studies identified several bacterial species that were significantly enriched in colorectal cancer patients. Some microbes were novel and their relationships with colorectal cancer were investigated, especially pinpointing the specific causative role of Peptostreptococcus anaerobius (Gastroenterology 2017b) and C. hathewayi (Cancer Res 2016) in CRC. The molecular bases of how the novel microbes play roles in the formation of colorectal cancer were investigated. Pertinent to clinical practice, we identified Fusobacterium as a marker to improve the diagnostic performance of the fecal immunochemical test, which could serve as non-invasive diagnostic markers for the early CRC (Gut 2017b; Clin Cancer Res 2017). In addition to our studies of the bacteriome, we identified for the first time CRC-associated virome signatures that independently predicted patient survival in CRC (Gastroenterology 2018). Moreover, we recently identified the enteric fungal microbiota dysbiosis in colorectal cancer (Gut 2018). The findings provide new insights for the molecular pathogenesis of CRC and aid development of new microbiome-based strategies for the diagnosis and prevention of this vital malignancy (Semin Cancer Biol 2018).
于君
香港中文大学消化疾病国家重点实验室
于君教授长期致力于消化系统肿瘤机制和防治研究,包括肠道微生态和肿瘤的研究10多年,获奖三十余项。发表SCI论文350多篇,影响因子10以上76篇;20以上14篇,包括: Nature、Nature Biotechnology, Cancer cell、Cell Metablism、J Clin Oncol、Sci Transl Med, JCI、Mol Cell、Gastroenterology、Hepatology、Gut、Nat Commun 等。
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The mammalian intestine contains trillions of microbes, a community that is dominated by members of the domain Bacteria but also includes members of Archaea, Eukarya, and viruses. The vast repertoire of this microbiome functions in ways that benefit the host. The mucosal immune system co-evolves with the microbiota beginning at birth, acquiring the capacity to tolerate components of the community while maintaining the capacity to respond to invading pathogens. The gut microbiota is shaped and regulated by multiple factors including our genomic composition, the local intestinal niche and multiple environmental factors including our nutritional repertoire and bio-geographical location. Moreover, it has been recently highlighted that dysregulation of these genetic or environmental factors leads to aberrant hostmicrobiome interactions, ultimately predisposing to pathologies ranging from chronic inflammation, obesity, the metabolic syndrome and even cancer. We have identified various possible mechanisms participating in the reciprocal regulation between the host and the intestinal microbial ecosystem, and demonstrate that disruption of these factors, in mice and humans, lead to dysbiosis and susceptibility to common multi-factorial disease. Understanding the molecular basis of host-microbiome interactions may lead to development of new microbiome-targeting treatments.
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