Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Harvard T.H. Chan Microbiome in Public Health Center, Boston, MA, USA.
Gut Microbes. 2024 Jan-Dec;16(1):2392874. doi: 10.1080/19490976.2024.2392874. Epub 2024 Aug 20.
Alterations in intestinal permeability and the gut microbiome caused by alcohol abuse are associated with alcoholic liver disease and with worsening of inflammatory bowel diseases (IBD) symptoms. To resolve the direct effects of chronic ethanol consumption on the colon and its microbiome in the absence of acute or chronic alcohol-induced liver disease, we developed a mouse model of chronic binge drinking that uncovers how alcohol may enhance susceptibility to colitis via the microbiota. Employing daily ethanol gavage, we recapitulate key features of binge ethanol consumption. We found that binge ethanol drinking worsens intestinal infection, colonic injury and inflammation, and this effect persists beyond the drinking period. Using gnotobiotics, we showed that alcohol-driven susceptibility to colitis is microbiota-dependent and transferable to ethanol-naïve mice by microbiome transplantation. . expanded in binge drinking mice, and administration of was sufficient to enhance colitis in non-drinking mice. Our study provides a model to study binge drinking-microbiota interactions and their effects on host disease and reinforces the pathogenic function of spp. as colitogenic bacteria. Our findings illustrate how chronic binge drinking-induced alterations of the microbiome may affect susceptibility to IBD onset or flares.
肠道通透性和肠道微生物组的改变是由酗酒引起的,与酒精性肝病和炎症性肠病(IBD)症状恶化有关。为了解决慢性乙醇摄入对结肠及其微生物组的直接影响,而不存在急性或慢性酒精性肝病,我们开发了一种慢性 binge 饮酒的小鼠模型,揭示了酒精如何通过微生物组增强结肠炎易感性。通过每日乙醇灌胃,我们重现了 binge 乙醇消耗的关键特征。我们发现 binge 乙醇饮酒会加重肠道感染、结肠损伤和炎症,而且这种影响会持续到饮酒期之外。使用无菌动物,我们表明,酒精驱动的结肠炎易感性依赖于微生物组,并且可以通过微生物组移植转移到乙醇-naïve 小鼠。在 binge 饮酒小鼠中扩增,并且施用 足以增强非饮酒小鼠的结肠炎。我们的研究提供了一个模型来研究 binge 饮酒-微生物组相互作用及其对宿主疾病的影响,并强化了 spp. 作为结肠炎细菌的致病功能。我们的发现说明了慢性 binge 饮酒引起的微生物组改变如何影响 IBD 发病或发作的易感性。