肠道微生物组组成与多种疾病相关，但对其与长期结果指标的关系知之甚少。虽然肠道菌群失调与普通人群的死亡风险有关，但其与特定疾病总生存率的关系尚未得到广泛研究。在当前的研究中，我们展示了对实体器官移植受者 (SOTR) 肠道菌群失调与全因和特定原因死亡率之间关系的深入分析结果。我们分析了来自以下人群粪便样本的 1337 个宏基因组： TransplantLines 生物库和队列研究包括 766 个肾脏、334 个肝脏、170 个肺和 67 个心脏移植受者，这是一项前瞻性队列研究，包括广泛的表型数据和 6.5 年的随访。为了分析肠道菌群失调，我们纳入了来自同一地理区域（荷兰北部）一般人群的额外 8208 个宏基因组。使用多变量 Cox 回归和机器学习算法来分析肠道菌群失调的多个指标之间的关联，包括个体物种丰度以及全因和特定原因死亡率。我们确定了代表总体微生物组群落变化的两种模式，这两种模式与全因死亡率和特定原因死亡率。每个移植接受者的肠道微生物组与一般人群平均水平之间的距离与全因死亡率以及感染、恶性肿瘤和心血管疾病导致的死亡相关。对单个物种丰度的多变量 Cox 回归确定了与全因死亡率相关的 23 种细菌物种，并通过应用机器学习算法，我们确定了由 23 种细菌中的 19 种组成的平衡（一种对数比）与全因死亡率相关。肠道菌群失调始终与 SOTR 的死亡率相关。我们的结果支持肠道菌群失调与长期生存相关的观察结果。由于我们的数据不允许我们推断因果关系，因此需要进行更多的临床前研究来了解机制，然后才能确定肠道微生物组导向的疗法是否可以改善长期结果。©作者（或其雇主） )) 2024 年。禁止商业重复使用。请参阅权利和权限。英国医学杂志出版。

Gut microbiome composition is associated with multiple diseases, but relatively little is known about its relationship with long-term outcome measures. While gut dysbiosis has been linked to mortality risk in the general population, the relationship with overall survival in specific diseases has not been extensively studied. In the current study, we present results from an in-depth analysis of the relationship between gut dysbiosis and all-cause and cause-specific mortality in the setting of solid organ transplant recipients (SOTR).We analysed 1337 metagenomes derived from faecal samples of 766 kidney, 334 liver, 170 lung and 67 heart transplant recipients part of the TransplantLines Biobank and Cohort-a prospective cohort study including extensive phenotype data with 6.5 years of follow-up. To analyze gut dysbiosis, we included an additional 8208 metagenomes from the general population of the same geographical area (northern Netherlands). Multivariable Cox regression and a machine learning algorithm were used to analyse the association between multiple indicators of gut dysbiosis, including individual species abundances, and all-cause and cause-specific mortality.We identified two patterns representing overall microbiome community variation that were associated with both all-cause and cause-specific mortality. The gut microbiome distance between each transplantation recipient to the average of the general population was associated with all-cause mortality and death from infection, malignancy and cardiovascular disease. A multivariable Cox regression on individual species abundances identified 23 bacterial species that were associated with all-cause mortality, and by applying a machine learning algorithm, we identified a balance (a type of log-ratio) consisting of 19 out of the 23 species that were associated with all-cause mortality.Gut dysbiosis is consistently associated with mortality in SOTR. Our results support the observations that gut dysbiosis is associated with long-term survival. Since our data do not allow us to infer causality, more preclinical research is needed to understand mechanisms before we can determine whether gut microbiome-directed therapies may be designed to improve long-term outcomes.© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.