炎症性肠病(IBDs)包括克罗恩病(CD)和溃疡性结肠炎(UC),其特征是慢性和衰弱性肠道炎症。肠道细菌群落的改变与IBD的发生和进展密切相关。肠道病毒,主要由细菌病毒(噬菌体,噬菌体),被认为是调节和塑造肠道微生物群落的重要因素。虽然已经在IBD患者中观察到肠道病毒改变,这些病毒对IBD患者相关的细菌群落改变和炎症反应增强的作用仍在很大程度上未知.
这里,我们进行了体内微生物交叉感染实验,以观察从UC患者和健康对照中分离的粪便病毒样颗粒(VLP)对人类微生物群相关(HMA)小鼠实验性结肠炎的细菌多样性和严重程度的影响.鸟枪宏基因组学证实,几种噬菌体被转移到HMA小鼠中,导致肠道病毒的治疗特异性改变。来自健康和UC患者的VLP也改变了这些小鼠的肠道细菌多样性,在实验性结肠炎期间放大的效应。从UC患者分离的VLP特异性改变了先前与IBD进展有关的几种细菌分类群的相对丰度。此外,UCVLP给药增加了HMA小鼠结肠炎的严重程度,如结肠长度缩短和促炎细胞因子产生增加所示。重要的是,这种效应依赖于完整的VLP。
我们的发现建立在最近的文献上,表明噬菌体是肠道细菌群落的动态调节因子,并暗示肠道病毒在调节肠道炎症和疾病中。视频摘要。
BACKGROUND: Inflammatory bowel diseases (IBDs) including Crohn\'s disease (CD) and ulcerative colitis (UC) are characterized by chronic and debilitating gut inflammation. Altered bacterial communities of the intestine are strongly associated with IBD initiation and progression. The gut virome, which is primarily composed of bacterial viruses (bacteriophages, phages), is thought to be an important factor regulating and shaping microbial communities in the gut. While alterations in the gut virome have been observed in IBD patients, the contribution of these viruses to alterations in the bacterial community and heightened inflammatory responses associated with IBD patients remains largely unknown.
RESULTS: Here, we performed in vivo microbial cross-infection experiments to follow the effects of fecal virus-like particles (VLPs) isolated from UC patients and healthy controls on bacterial diversity and severity of experimental colitis in human microbiota-associated (HMA) mice. Shotgun metagenomics confirmed that several phages were transferred to HMA mice, resulting in treatment-specific alterations in the gut virome. VLPs from healthy and UC patients also shifted gut bacterial diversity of these mice, an effect that was amplified during experimental colitis. VLPs isolated from UC patients specifically altered the relative abundance of several bacterial taxa previously implicated in IBD progression. Additionally, UC VLP administration heightened colitis severity in HMA mice, as indicated by shortened colon length and increased pro-inflammatory cytokine production. Importantly, this effect was dependent on intact VLPs.
CONCLUSIONS: Our findings build on recent literature indicating that phages are dynamic regulators of bacterial communities in the gut and implicate the intestinal virome in modulating intestinal inflammation and disease. Video Abstract.