Role of Bile Acids in Human Susceptibiity to Clostridium difficile Infection

胆汁酸在人类对艰难梭菌感染易感性中的作用

• 批准号: 8682883
• 负责人: Yoav Golan
• 金额: $ 19.57万
• 依托单位: TUFTS UNIVERSITY BOSTON
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-06-15 至 2015-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8682883
• 关键词: Anaerobic Bacteria; Anti-Infective Agents; Antibiotic Therapy; Antibiotics; Appearance; Bacteria; Bacteroides; Bile Acids; Bile fluid; Biological Assay; Blinded; Characteristics; Cholates; Clostridium; Clostridium difficile; Colon; Communities; Community-Acquired Infections; Detection; Diagnosis; Diagnostic; Diarrhea; Disease; Disease Outbreaks; Disease Outcome; Elderly; Exposure to; Family; Feces; Frequencies; Gastrointestinal tract structure; Germination; Growth; Hospitals; Human; Infection; Inflammation; Intestines; Laboratories; Liver; Metabolic; Metabolism; Metronidazole; North America; Nosocomial Infections; Patients; Predisposition; Proteins; Recurrence; Relapse; Relative (related person); Reproduction spores; Research Personnel; Resistance; Risk; Risk Factors; Role; Sampling; Severities; Specimen; Symptoms; Taurine Cholate; Taurocholate Sodium; Toxin; Vaccines; Vancomycin; Virulence Factors; Work; absorption; analog; bile salts; chenodeoxycholate; combat; deoxycholate; factor C; high risk; hydroxyl group; intestinal epithelium; killings; member; novel; prevent; prospective; public health relevance; research study; tertiary care

DESCRIPTION (provided by applicant): Clostridium difficile has become the most frequent cause of antibiotic-associated diarrhea. Moreover, the need to prevent/treat C. difficile infection (CDI) effectively has become more urgent as the severity of CDI has increased. Whereas in the past CDI was rarely a fatal disease, it now kills a significant number of patients, especially among the elderly or immunologically suppressed. Currently employed antibiotics (chiefly vancomycin and metronidazole) fail to eliminate CDI symptoms in 10-20% of patients. In addition, among those apparently cured, a significant fraction suffers multiple recurrences of CDI. In principle, it is better to prevent the occurrence of infection than to rely on post-infectin treatments. The infectious form of C. difficile is the spore; once spores enter the GI tract, they must germinate in order to return to vegetative growth, colonize and produce the toxin proteins that cause the symptoms of the disease. Previous work has shown that C. difficile spore germination is dependent on certain bile acids. The most effective germinant identified so far is the primary bile salt, sodium taurocholate. A metabolic product of taurocholate, deoxycholate, is produced by the normal microflora and is known to kill C. difficile. Interestingly, bile acids of te chenodeoxycholate family, which differ from the cholate family by a single hydroxyl group, are anti-germinant that competitively inhibit taurocholate-dependent germination. These findings have raised the possibility that certain bile acids or their derivatives could be used prophylactically to reduce the likelihood of CDI in patients who are at risk. Before doing so, however, it is critical to establish that patients who have CDI or who are at risk of becoming infected have an intestinal bile acid profile that favors C. difficile spore germination. If so, on could imagine delivering appropriate anti-germinant or growth-inhibiting bile acids to patients at risk to prevent the onset on CDI. In this proposal, we seek to reveal the relationship between bile acid profiles and likelihood of CDI by analyzing the bile acid profiles and presence of certai key members of the microflora in patients with CDI, in patients undergoing antibiotic therapy (which is a major risk factor for CDI) and in patients with recurrent CDI.

描述（由申请人提供）：艰难梭菌已成为抗生素相关性腹泻的最常见原因。此外，需要预防/治疗艰难梭菌感染