Division of Hematology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
PLoS One. 2020 Oct 28;15(10):e0236460. doi: 10.1371/journal.pone.0236460. eCollection 2020.
The intestinal bacterial flora of febrile neutropenic patients has been found to be significantly diverse. However, there are few reports of alterations of in adult acute myeloid leukemia (AML) patients. Stool samples of each treatment-naïve AML patient were collected the day before initiation of induction chemotherapy (pretreatment), on the first date of neutropenic fever and first date of bone marrow recovery. Bacterial DNA was extracted from stool samples and bacterial 16s ribosomal RNA genes were sequenced by next-generation sequencing. Relative abundance, overall richness, Shannon's diversity index and Simpson's diversity index were calculated. No antimicrobial prophylaxis was in placed in all participants. Ten cases of AML patients (4 male and 6 female) were included with a median age of 39 years (range: 19-49) and all of patients developed febrile neutropenia. Firmicutes dominated during the period of neutropenic fever, subsequently declining after bone marrow recovery a pattern in contrast to that shown by Bacteroidetes and Proteobacteria. Enterococcus was more abundant in the febrile neutropenia period compared to pretreatment (mean difference +20.2; p < 0.0001) while Escherichia notably declined during the same period (mean difference -11.2; p = 0.0064). At the operational taxonomic unit (OTU) level, there was a significantly higher level of overall richness in the pretreatment period than in the febrile neutropenic episode (mean OTU of 203.1 vs. 131.7; p = 0.012). Both of the diversity indexes of Shannon and Simpson showed a significant decrease during the febrile neutropenic period. Adult AML patients with a first episode of febrile neutropenia after initial intensive chemotherapy demonstrated a significant decrease in gut microbiota diversity and the level of diversity remained constant despite recovery of bone marrow.
发热性中性粒细胞减少症患者的肠道细菌菌群存在明显的多样性。然而，成人急性髓系白血病（AML）患者的相关改变报道较少。在诱导化疗开始前一天（预处理）、中性粒细胞减少性发热的第一天和骨髓恢复的第一天，采集每个初治 AML 患者的粪便样本。从粪便样本中提取细菌 DNA，并通过下一代测序对细菌 16s 核糖体 RNA 基因进行测序。计算相对丰度、总体丰富度、香农多样性指数和辛普森多样性指数。所有参与者均未进行抗生素预防。纳入了 10 例 AML 患者（4 例男性和 6 例女性），中位年龄为 39 岁（范围：19-49），所有患者均发生发热性中性粒细胞减少症。在中性粒细胞减少性发热期间，厚壁菌门占主导地位，随后在骨髓恢复后下降，与拟杆菌门和变形菌门的模式相反。与预处理相比，肠球菌在发热性中性粒细胞减少症期间更为丰富（平均差异+20.2；p<0.0001），而大肠杆菌在同一时期明显减少（平均差异-11.2；p=0.0064）。在操作分类单元（OTU）水平，预处理期的总体丰富度明显高于发热性中性粒细胞减少期（预处理期平均 OTU 为 203.1，发热性中性粒细胞减少期为 131.7；p=0.012）。Shannon 和 Simpson 的多样性指数在发热性中性粒细胞减少期间均显著下降。初始强化化疗后首次发生发热性中性粒细胞减少症的成人 AML 患者，肠道微生物多样性显著下降，尽管骨髓恢复，但多样性水平保持不变。
