Shin Jae Hyun, High Kevin P, Warren Cirle A
Division of Infectious Diseases and International Health, University of Virginia, Charlottesville.
Section of Infectious Diseases, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina.
J Gerontol A Biol Sci Med Sci. 2016 Jul;71(7):916-22. doi: 10.1093/gerona/glv229. Epub 2016 Jan 25.
Clostridium difficile infection (CDI) is the most common cause of antibiotic-associated diarrhea and a significant burden on the health care system. Aging has been identified in the literature as a risk factor for CDI as well as adverse outcome from CDI. Although this effect of advanced age on CDI could be partially explained by clinical factors associated with aging, biologic factors are important. Innate immune system, responsible for immediate response to acute infections, plays a major role in CDI pathogenesis. Impairment in function of innate immunity with aging, demonstrated in other infection models, may lead to worse outcome with CDI. C. difficile toxin-specific antibody response protects the host against initial and recurrent infections as shown in observational studies and clinical trial. Effect of aging on antibody response to CDI has not been demonstrated, but the results from vaccine studies in other infections suggest a negative effect on humoral immunity from aging. Although intestinal microbiota from healthy people confers resistance to CDI by preventing C. difficile colonization, changes in composition of microbiota with aging may affect that resistance and increase risk for CDI. There are also age-associated changes in physiology, especially of the gastrointestinal tract, that may play a role in CDI risk and outcomes. In this review, we will first discuss the epidemiology of CDI in the elderly people, then the alteration in innate immunity, humoral response, and microbiota that increases susceptibility to CDI and severe disease and lastly, the physiological and functional changes that may modify outcomes of infection.
艰难梭菌感染（CDI）是抗生素相关性腹泻最常见的病因，也是医疗保健系统的一项重大负担。文献已将衰老确定为CDI的一个风险因素以及CDI不良结局的一个风险因素。尽管高龄对CDI的这种影响可能部分由与衰老相关的临床因素所解释，但生物学因素也很重要。负责对急性感染做出即时反应的固有免疫系统在CDI发病机制中起主要作用。在其他感染模型中已证实，随着衰老，固有免疫功能受损可能导致CDI出现更差的结局。观察性研究和临床试验表明，艰难梭菌毒素特异性抗体反应可保护宿主抵御初次感染和复发性感染。衰老对CDI抗体反应的影响尚未得到证实，但其他感染疫苗研究的结果表明衰老对体液免疫有负面影响。尽管健康人的肠道微生物群通过阻止艰难梭菌定植赋予对CDI的抵抗力，但随着衰老，微生物群组成的变化可能会影响这种抵抗力并增加CDI风险。生理方面也存在与年龄相关的变化，尤其是胃肠道的变化，这可能在CDI风险和结局中起作用。在本综述中，我们将首先讨论老年人CDI的流行病学，然后讨论固有免疫、体液反应和微生物群的改变，这些改变会增加对CDI和严重疾病的易感性，最后讨论可能改变感染结局的生理和功能变化。
