Metabolism and Nutrition Research Group, Louvain Drug Research Institute, UCLouvain, Université catholique de Louvain, Brussels, Belgium.
Department of Hematology, Cliniques Universitaires Saint-Luc, UCLouvain, Université catholique de Louvain, Brussels, Belgium; Experimental Medicine Unit, De Duve Institute, UCLouvain, Université catholique de Louvain, Brussels, Belgium.
Clin Nutr. 2023 Nov;42(11):2214-2228. doi: 10.1016/j.clnu.2023.09.021. Epub 2023 Sep 25.
BACKGROUND & AIMS: Acute myeloid leukaemia (AML) chemotherapy has been reported to impact gut microbiota composition. In this study, we investigated using a multi -omics strategy the changes in the gut microbiome induced by AML intense therapy and their association with gut barrier function and cachectic hallmarks.
10 AML patients, allocated to standard induction chemotherapy (SIC), were recruited. Samples and data were collected before any therapeutic intervention (T0), at the end of the SIC (T1) and at discharge (T4). Gut microbiota composition and function, markers of inflammation, metabolism, gut barrier function and cachexia, as well as faecal, blood and urine metabolomes were assessed.
AML patients demonstrated decreased appetite, weight loss and muscle wasting during hospitalization, with an incidence of cachexia of 50%. AML intensive treatment transiently impaired the gut barrier function and led to a long-lasting change of gut microbiota composition characterized by an important loss of diversity. Lactobacillaceae and Campylobacter concisus were increased at T1 while Enterococcus faecium and Staphylococcus were increased at T4. Metabolomics analyses revealed a reduction in urinary hippurate and faecal bacterial amino acid metabolites (bAAm) (2-methylbutyrate, isovalerate, phenylacetate). Integration using DIABLO revealed a deep interconnection between all the datasets. Importantly, we identified bacteria which disappearance was associated with impaired gut barrier function (Odoribacter splanchnicus) and body weight loss (Gemmiger formicilis), suggesting these bacteria as actionable targets.
AML intensive therapy transiently impairs the gut barrier function while inducing enduring alterations in the composition and metabolic activity of the gut microbiota that associate with body weight loss.
NCT03881826, https://clinicaltrials.gov/ct2/show/NCT03881826.
急性髓系白血病（AML）的化疗已被报道会影响肠道微生物群落组成。在这项研究中，我们采用多组学策略研究了 AML 强化治疗引起的肠道微生物组变化及其与肠道屏障功能和恶病质特征的关系。
招募了 10 名 AML 患者，分为标准诱导化疗（SIC）组。在任何治疗干预前（T0）、SIC 结束时（T1）和出院时（T4）采集样本和数据。评估肠道微生物群落组成和功能、炎症标志物、代谢物、肠道屏障功能和恶病质，以及粪便、血液和尿液代谢组学。
AML 患者在住院期间表现出食欲下降、体重减轻和肌肉减少，恶病质发生率为 50%。AML 强化治疗短暂损害肠道屏障功能，并导致肠道微生物群落组成的持久变化，其特征是多样性显著丧失。T1 时乳杆菌科和弯曲杆菌属 C. concisus 增加，而 T4 时粪肠球菌和金黄色葡萄球菌增加。代谢组学分析显示尿中马尿酸和粪便细菌氨基酸代谢物（bAAm）（2-甲基丁酸、异戊酸、苯乙酸）减少。使用 DIABLO 进行整合分析显示，所有数据集之间存在深度关联。重要的是，我们确定了与肠道屏障功能受损（Odoribacter splanchnicus）和体重减轻（Gemmiger formicilis）相关的细菌消失，提示这些细菌是可操作的靶点。
AML 强化治疗短暂损害肠道屏障功能，同时诱导肠道微生物群落组成和代谢活性的持久改变，与体重减轻相关。
NCT03881826，https://clinicaltrials.gov/ct2/show/NCT03881826。
