Dela Cruz Mark, Lin Huaiying, Han Jiho, Adler Emerald, Boissiere Jaye, Khalid Maryam, Sidebottom Ashley, Sundararajan Anitha, Lehmann Christopher, Moran Angelica, Odenwald Matthew, Stutz Matthew, Kim Gene, Pinney Sean, Jeevanandam Valluvan, Alegre Maria-Luisa, Pamer Eric, Nguyen Ann B
Department of Medicine, Section of Cardiology, University of Chicago Medicine, Chicago, IL, United States.
Duchossois Family Institute, University of Chicago, Chicago, IL, United States.
Front Transplant. 2023 Jul 17;2:1182534. doi: 10.3389/frtra.2023.1182534. eCollection 2023.
Emerging evidence is revealing the impact of the gut microbiome on hematopoietic and solid organ transplantation. Prior studies postulate that this influence is mediated by bioactive metabolites produced by gut-dwelling commensal bacteria. However, gut microbial metabolite production has not previously been measured among heart transplant (HT) recipients.
In order to investigate the potential influence of the gut microbiome and its metabolites on HT, we analyzed the composition and metabolite production of the fecal microbiome among 48 HT recipients at the time of HT.
Compared to 20 healthy donors, HT recipients have significantly reduced alpha, i.e. within-sample, microbiota diversity, with significantly lower abundances of key anaerobic commensal bacteria and higher abundances of potentially pathogenic taxa that have been correlated with adverse outcomes in other forms of transplantation. HT recipients have a wide range of microbiota-derived fecal metabolite concentrations, with significantly reduced levels of immune modulatory metabolites such as short chain fatty acids and secondary bile acids compared to healthy donors. These differences were likely due to disease severity and prior antibiotic exposures but were not explained by other demographic or clinical factors.
Key potentially immune modulatory gut microbial metabolites are quantifiable and significantly reduced among HT recipients compared to healthy donors. Further study is needed to understand whether this wide range of gut microbial dysbiosis and metabolite alterations impact clinical outcomes and if they can be used as predictive biomarkers or manipulated to improve transplant outcomes.
新出现的证据揭示了肠道微生物群对造血和实体器官移植的影响。先前的研究推测，这种影响是由肠道共生细菌产生的生物活性代谢产物介导的。然而，此前尚未在心脏移植（HT）受者中测量肠道微生物代谢产物的产生情况。
为了研究肠道微生物群及其代谢产物对心脏移植的潜在影响，我们分析了48名心脏移植受者在心脏移植时粪便微生物群的组成和代谢产物的产生情况。
与20名健康供体相比，心脏移植受者的α多样性（即样本内微生物群多样性）显著降低，关键厌氧共生细菌的丰度显著降低，而与其他形式移植的不良结局相关的潜在致病类群的丰度更高。心脏移植受者有广泛的微生物群衍生的粪便代谢产物浓度，与健康供体相比，免疫调节代谢产物如短链脂肪酸和次级胆汁酸的水平显著降低。这些差异可能归因于疾病严重程度和先前的抗生素暴露，但未被其他人口统计学或临床因素所解释。
与健康供体相比，心脏移植受者中关键的潜在免疫调节性肠道微生物代谢产物是可量化的，且显著减少。需要进一步研究以了解这种广泛的肠道微生物失调和代谢产物改变是否会影响临床结局，以及它们是否可用作预测生物标志物或加以调控以改善移植结局。
