Department of Medicine and Surgery, University of Parma, Parma, Italy.
Dipartimento Medico-Geriatrico-Riabilitativo, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy.
Sci Rep. 2017 Sep 11;7(1):11102. doi: 10.1038/s41598-017-10734-y.
Reduced biodiversity and increased representation of opportunistic pathogens are typical features of gut microbiota composition in aging. Few studies have investigated their correlation with polypharmacy, multimorbidity and frailty. To assess it, we analyzed the fecal microbiota from 76 inpatients, aged 83 ± 8. Microbiome biodiversity (Chao1 index) and relative abundance of individual bacterial taxa were determined by next-generation 16S rRNA microbial profiling. Their correlation with number of drugs, and indexes of multimorbidity and frailty were verified using multivariate linear regression models. The impact of gut microbiota biodiversity on mortality, rehospitalizations and incident sepsis was also assessed after a 2-year follow-up, using Cox regression analysis. We found a significant negative correlation between the number of drugs and Chao1 Index at multivariate analysis. The number of drugs was associated with the average relative abundance of 15 taxa. The drug classes exhibiting the strongest association with single taxa abundance were proton pump inhibitors, antidepressants and antipsychotics. Conversely, frailty and multimorbidity were not significantly associated with gut microbiota biodiversity. Very low Chao1 index was also a significant predictor of mortality, but not of rehospitalizations and sepsis, at follow-up. In aging, polypharmacy may thus represent a determinant of gut microbiota composition, with detrimental clinical consequences.
肠道微生物群落组成在衰老过程中呈现出生物多样性减少和机会性病原体增多的特征。很少有研究调查它们与多种药物治疗、多种合并症和衰弱之间的相关性。为了评估这一点,我们分析了 76 名年龄在 83±8 岁的住院患者的粪便微生物群。通过下一代 16S rRNA 微生物分析,确定了微生物组的生物多样性(Chao1 指数)和个体细菌分类群的相对丰度。使用多元线性回归模型验证了它们与药物数量以及多种合并症和衰弱指数的相关性。使用 Cox 回归分析还评估了肠道微生物群落生物多样性对 2 年后死亡率、再入院和感染性败血症的影响。我们在多变量分析中发现药物数量与 Chao1 指数呈显著负相关。药物数量与 15 个分类群的平均相对丰度相关。与单个分类群丰度相关性最强的药物类别是质子泵抑制剂、抗抑郁药和抗精神病药。相反,衰弱和多种合并症与肠道微生物群落生物多样性没有显著相关性。Chao1 指数非常低也是随访期间死亡率的一个显著预测因素,但不是再入院率和败血症的预测因素。因此,在衰老过程中,多种药物治疗可能是肠道微生物群落组成的一个决定因素,具有潜在的临床不良后果。