J. Craig Venter Institute (JCVI), Rockville, MD, USA.
Division of Infectious Diseases, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Microb Ecol. 2020 May;79(4):1034-1043. doi: 10.1007/s00248-019-01448-x. Epub 2019 Nov 21.
Prophylactic or therapeutic antibiotic use along with chemotherapy treatment potentially has a long-standing adverse effect on the resident gut microbiota. We have established a case-control cohort of 32 pediatric and adolescent acute lymphoblastic leukemia (ALL) patients and 25 healthy siblings (sibling controls) to assess the effect of chemotherapy as well as antibiotic prophylaxis on the gut microbiota. We observe that the microbiota diversity and richness of the ALL group is significantly lower than that of the control group at diagnosis and during chemotherapy. The microbiota diversity is even lower in antibiotics-exposed ALL patients. Although the gut microbial diversity tends to stabilize after 1-year post-chemotherapy, their abundances were altered because of chemotherapy and prophylactic antibiotic treatments. Specifically, the abundances of mucolytic gram-positive anaerobic bacteria, including Ruminococcus gnavus and Ruminococcus torques, tended to increase during the chemotherapy regimen and continued to be elevated 1 year beyond the initiation of chemotherapy. This dysbiosis may contribute to the development of gastrointestinal complications in ALL children following chemotherapy. These findings set the stage to further understand the role of the gut microbiome dynamics in ALL patients and their potential role in alleviating some of the adverse side effects of chemotherapy and antibiotics use in immunocompromised children.
预防性或治疗性使用抗生素与化疗治疗相结合，可能对常驻肠道微生物群产生长期的不良影响。我们建立了一个由 32 名儿科和青少年急性淋巴细胞白血病（ALL）患者和 25 名健康兄弟姐妹（兄弟姐妹对照组）组成的病例对照队列，以评估化疗以及抗生素预防对肠道微生物群的影响。我们观察到，在诊断时和化疗期间，ALL 组的微生物多样性和丰富度明显低于对照组。接受抗生素治疗的 ALL 患者的微生物多样性甚至更低。尽管在化疗后 1 年，肠道微生物多样性趋于稳定，但由于化疗和预防性抗生素治疗，其丰度发生了改变。具体而言，在化疗期间，包括 Ruminococcus gnavus 和 Ruminococcus torques 在内的黏液分解革兰氏阳性厌氧菌的丰度趋于增加，并在化疗开始后 1 年仍持续升高。这种肠道微生态失调可能导致 ALL 儿童在化疗后出现胃肠道并发症。这些发现为进一步了解肠道微生物组动态在 ALL 患者中的作用以及它们在减轻免疫功能低下儿童化疗和抗生素使用的一些不良副作用方面的潜在作用奠定了基础。
