The intestinal microbiome is emerging as a crucial mediator between external insults and systemic infections. New research suggests that our intestinal microorganisms contribute to critical illness and the development...The intestinal microbiome is emerging as a crucial mediator between external insults and systemic infections. New research suggests that our intestinal microorganisms contribute to critical illness and the development of non-gastrointestinal infectious diseases.Common pathways include a loss of fecal intestinal bacterial diversity and a disproportionate increase in toxogenic bacterial species. Therapeutic interventions targeting the microbiome- primarily probiotics- have yielded limited results to date. However, knowledge in this area is rapidly expanding and microbiome-based therapy such as short-chain fatty acids may eventually become a standard strategy for preventing systemic infections in the context of critical illness.展开更多
Although antagonists of tumor necrosis factor have resulted in major therapeutic benefits in inflammatory bowel disease, the magnitude and durability of response are variable. Similar to previously available drugs suc...Although antagonists of tumor necrosis factor have resulted in major therapeutic benefits in inflammatory bowel disease, the magnitude and durability of response are variable. Similar to previously available drugs such as 5-aminosalicylates and immunomodulators, the therapeutic effect is not universal leaving many people searching for options. The development of newer agents has benefited from advances in the understanding of the pathophysiology of the disease. Uncontrolled activation of the acquired immune system has an important role, and lymphocytes, cytokines, and adhesion molecules are broadly targeted for therapeutic intervention. There is increasing evidence of an important role of the innate immune system and the intestinal epithelium, and the therapeutic paradigm is also shifting from immunosuppression to the reinforcement of the intestinal barrier, and modification of the disease process. In this review, we explore the limitation of current therapy as well as mechanisms of actions of new drugs and the efficacy and adverse events from data from clinical trials.展开更多
基金Supported by Mentored Career Development Award through the National Center for Advancing Translational Sciences’Clinical and Translational Science Awards program,No.NIH KL2 TR000081(in part)
文摘The intestinal microbiome is emerging as a crucial mediator between external insults and systemic infections. New research suggests that our intestinal microorganisms contribute to critical illness and the development of non-gastrointestinal infectious diseases.Common pathways include a loss of fecal intestinal bacterial diversity and a disproportionate increase in toxogenic bacterial species. Therapeutic interventions targeting the microbiome- primarily probiotics- have yielded limited results to date. However, knowledge in this area is rapidly expanding and microbiome-based therapy such as short-chain fatty acids may eventually become a standard strategy for preventing systemic infections in the context of critical illness.
文摘Although antagonists of tumor necrosis factor have resulted in major therapeutic benefits in inflammatory bowel disease, the magnitude and durability of response are variable. Similar to previously available drugs such as 5-aminosalicylates and immunomodulators, the therapeutic effect is not universal leaving many people searching for options. The development of newer agents has benefited from advances in the understanding of the pathophysiology of the disease. Uncontrolled activation of the acquired immune system has an important role, and lymphocytes, cytokines, and adhesion molecules are broadly targeted for therapeutic intervention. There is increasing evidence of an important role of the innate immune system and the intestinal epithelium, and the therapeutic paradigm is also shifting from immunosuppression to the reinforcement of the intestinal barrier, and modification of the disease process. In this review, we explore the limitation of current therapy as well as mechanisms of actions of new drugs and the efficacy and adverse events from data from clinical trials.
