Linking gastrointestinal microbiota and metabolome dynamics to clinical outcomes in paediatric haematopoietic stem cell transplantation.
Linking gastrointestinal microbiota and metabolome dynamics to clinical outcomes in paediatric haematopoietic stem cell transplantation.
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DOI：
10.1186/s40168-022-01270-7
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发表时间：
2022-06-10
期刊：
影响因子：
15.5
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中科院分区：
文献类型：
--
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造血干细胞移植是一种治疗多种疾病的方法。尽管取得了重大进展，但移植后可能出现大量不良临床结果，包括移植物抗宿主病和感染，这仍然是发病率和死亡率的主要原因。越来越多的证据表明，胃肠道微生物群与造血干细胞移植后的临床结果相关。在此，我们研究了单一中心儿童造血干细胞移植中肠道微生物群和代谢组的纵向动态以及与临床结果的潜在关联。入院时（基线），与α多样性显著降低的健康对照儿童相比，大多数患者呈现出不同的肠道微生物组成。此外，移植后立即观察到α多样性和大多数微生物多样性显着下降，并且在住院期间组成没有恢复到基线状态。纵向轨迹确定了微生物组成的持续波动，在相当大比例的患者中，单一分类群占主导地位。使用pam聚类，在数据集中观察到三个聚类。聚类1为常见的移植前菌群，以Clostridium XIVa、Bacteroides和Lachnospiraceae的丰度较高为特征；移植后簇2和簇3更为常见，前者以链球菌和葡萄球菌丰度较高，后者以肠球菌、肠杆菌科和埃希氏菌为主。第3组也与较高的病毒血症风险相关。同样，进一步的多变量分析显示肠杆菌科、病毒血症、全肠外营养和各种抗菌剂的使用对第3类起作用，链球菌科、葡萄球菌科、奈瑟菌科、万古霉素和甲硝唑对第2类起作用。毛螺杆菌科、瘤胃球菌科、双歧杆菌科和未接受全肠外营养的细菌组成了第1群。非靶向代谢组学分析揭示了微生物群组成的平行波动变化；重要的是，低丁酸盐粪便与病毒血症的高风险相关。这些发现强调了接受造血干细胞移植的儿科患者肠道微生物群的频繁变化和优势。这项研究揭示了粪便微生物群、代谢组和病毒血症之间的联系。为了识别和探索可能预测造血干细胞移植后并发症风险的微生物生物标志物的潜力，有必要进行更大规模的多中心研究，调查儿科造血干细胞移植的纵向微生物谱。视频摘要。在线版本包含补充材料，可在10.1186/s40168-022-01270-7获得。
Haematopoietic stem cell transplantation is a curative procedure for a variety of conditions. Despite major advances, a plethora of adverse clinical outcomes can develop post-transplantation including graft-versus-host disease and infections, which remain the major causes of morbidity and mortality. There is increasing evidence that the gastrointestinal microbiota is associated with clinical outcomes post-haematopoietic stem cell transplantation. Herein, we investigated the longitudinal dynamics of the gut microbiota and metabolome and potential associations to clinical outcomes in paediatric haematopoietic stem cell transplantation at a single centre. On admission (baseline), the majority of patients presented with a different gut microbial composition in comparison with healthy control children with a significantly lower alpha diversity. A further, marked decrease in alpha diversity was observed immediately post-transplantation and in most microbial diversity, and composition did not return to baseline status whilst hospitalised. Longitudinal trajectories identified continuous fluctuations in microbial composition, with the dominance of a single taxon in a significant proportion of patients. Using pam clustering, three clusters were observed in the dataset. Cluster 1 was common pre-transplantation, characterised by a higher abundance of Clostridium XIVa, Bacteroides and Lachnospiraceae; cluster 2 and cluster 3 were more common post-transplantation with a higher abundance of Streptococcus and Staphylococcus in the former whilst Enterococcus, Enterobacteriaceae and Escherichia predominated in the latter. Cluster 3 was also associated with a higher risk of viraemia. Likewise, further multivariate analysis reveals Enterobacteriaceae, viraemia, use of total parenteral nutrition and various antimicrobials contributing towards cluster 3, Streptococcaceae, Staphylococcaceae, Neisseriaceae, vancomycin and metronidazole contributing towards cluster 2. Lachnospiraceae, Ruminococcaceae, Bifidobacteriaceae and not being on total parenteral nutrition contributed to cluster 1. Untargeted metabolomic analyses revealed changes that paralleled fluctuations in microbiota composition; importantly, low faecal butyrate was associated with a higher risk of viraemia. These findings highlight the frequent shifts and dominations in the gut microbiota of paediatric patients undergoing haematopoietic stem cell transplantation. The study reveals associations between the faecal microbiota, metabolome and viraemia. To identify and explore the potential of microbial biomarkers that may predict the risk of complications post-HSCT, larger multi-centre studies investigating the longitudinal microbial profiling in paediatric haematopoietic stem cell transplantation are warranted. Video abstract. The online version contains supplementary material available at 10.1186/s40168-022-01270-7.
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DOI：
10.1093/cid/ciz1186
发表时间：
2020-12-31
期刊：
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
影响因子：
--
作者：
D'Souza AW;Moodley-Govender E;Berla B;Kelkar T;Wang B;Sun X;Daniels B;Coutsoudis A;Trehan I;Dantas G
通讯作者：
Dantas G
DOI：
10.1016/j.bbmt.2014.01.030
发表时间：
2014-05
期刊：
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
影响因子：
--
作者：
Holler E;Butzhammer P;Schmid K;Hundsrucker C;Koestler J;Peter K;Zhu W;Sporrer D;Hehlgans T;Kreutz M;Holler B;Wolff D;Edinger M;Andreesen R;Levine JE;Ferrara JL;Gessner A;Spang R;Oefner PJ
通讯作者：
Oefner PJ
DOI：
10.1038/s41571-020-0356-4
发表时间：
2020-08
期刊：
Nature reviews. Clinical oncology
影响因子：
--
作者：
Blazar BR;Hill GR;Murphy WJ
通讯作者：
Murphy WJ
影响因子：
7.3
作者：
Annaloro C;Serpenti F;Saporiti G;Galassi G;Cavallaro F;Grifoni F;Goldaniga M;Baldini L;Onida F
通讯作者：
Onida F
影响因子：
4.3
作者：
Kelly, Matthew S.;Ward, Doyle V.;Seed, Patrick C.
通讯作者：
Seed, Patrick C.