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异基因造血干细胞移植后肠道菌群的时间依赖性变化、定植及抗生素耐药基因的发生率

Time-Dependent Shifts in Intestinal Bacteriome, Colonization and Incidence of Antibiotic-Resistance Genes after Allogeneic Hematopoietic Stem Cell Transplantation.

作者信息

Goloshchapov Oleg V, Chukhlovin Alexey B, Polev Dmitrii E, Eismont Yury A, Bug Dmitry S, Kusakin Alexey V, Kosarev Oleg V, Klementeva Ruslana V, Gostev Vladimir V, Ageevets Vladimir A, Volkov Nikita P, Ipatova Anastasia S, Moiseev Ivan S, Spiridonova Anna A, Sidorenko Sergey V, Kulagin Alexander D

机构信息

R. Gorbacheva Memorial Research Institute of Pediatric Oncology, Hematology and Transplantation, Pavlov First State Medical University of St. Petersburg, L. Tolstoy St, 6-8, 197022 St. Petersburg, Russia.

Pasteur Institute of Epidemiology and Microbiology, Mira St, 14, 197101 St. Petersburg, Russia.

出版信息

Biomedicines. 2024 Jul 15;12(7):1566. doi: 10.3390/biomedicines12071566.

Abstract

Dose-intensive cytostatic therapy and antibiotic treatment in allogeneic hematopoietic stem cell transplantation (allo-HSCT) cause severe abnormalities in a composition of gut microbiota as well as the emergence of antibiotic resistance. The data on the longitudinal recovery of major bacterial phyla and the expansion of genes associated with antibiotic resistance are limited. We collected regular stool samples during the first year after allo-HSCT from 12 adult patients with oncohematological disorders after allo-HSCT and performed 16SrRNA sequencing, multiplex PCR, conventional bacteriology and CHROMagar testing. We observed a decline in Shannon microbiota diversity index as early as day 0 of allo-HSCT ( = 0.034) before any administration of antibiotics, which persisted up to 1 year after transplantation, when the Shannon index returned to pre-transplant levels ( = 0.91). The study confirmed the previously shown decline in Bacillota (Firmicutes) genera and the expansion of /, and . The recovery of was slower than that of other phyla and occurred only a year post-transplant. A positive correlation was observed between the expansion of / genera and , and ( < 0.001), spp. and -like, , , , and ( < 0.001), spp. and ( = 0.002), spp. and -like, , , ( < 0.01). The correlation was observed between the expansion of Enterobacterales and and carbapenemase-positive CHROMagar samples ( < 0.001). Samples positive for carbapenem-resitant bacteria were at their maximum levels on day +30, and were gradually diminishing one year after allo-HSCT. From day +30 to +60, all isolated strains in fecal samples proved to be resistant to the main antibiotic groups (carbapenems, aminoglycosides, fluoroquinolones, third-generation cephalosporins). One year after HSCT, we documented the spontaneous decolonization of . The sensitivity of molecular biology techniques in the search for total and antibiotic-resistant seems to be superior to common bacteriological cultures. Future studies should be focused on searching for novel approaches to the efficient reconstitution and/or maintenance of strictly anaerobic microbiota in oncological patients.

摘要

异基因造血干细胞移植(allo-HSCT)中的剂量密集型细胞毒性疗法和抗生素治疗会导致肠道微生物群组成出现严重异常以及抗生素耐药性的出现。关于主要细菌门纵向恢复以及与抗生素耐药性相关基因扩增的数据有限。我们在allo-HSCT后的第一年,从12例患有血液肿瘤疾病的成年allo-HSCT患者中定期收集粪便样本,并进行16SrRNA测序、多重PCR、传统细菌学检测和CHROMagar检测。我们观察到,早在allo-HSCT的第0天( = 0.034),在尚未使用任何抗生素之前,香农微生物多样性指数就出现下降,这种下降一直持续到移植后1年,此时香农指数恢复到移植前水平( = 0.91)。该研究证实了之前所显示的芽孢杆菌门(厚壁菌门)属的减少以及 /、 和 属的扩增。 的恢复比其他门要慢,且仅在移植后一年才出现。观察到 / 属的扩增与 、 和 ( < 0.001)、 菌属与 -样菌、 、 、 ( < 0.001)、 菌属与 ( = 0.002)、 菌属与 -样菌、 、 ( < 0.01)之间存在正相关。观察到肠杆菌科的扩增与碳青霉烯酶阳性CHROMagar样本之间存在相关性( < 0.001)。耐碳青霉烯类细菌阳性样本在第30天达到最高水平,并在allo-HSCT后一年逐渐减少。从第30天到第60天,粪便样本中所有分离出的 菌株均对主要抗生素类别(碳青霉烯类、氨基糖苷类、氟喹诺酮类、第三代头孢菌素)耐药。HSCT后一年,我们记录到了 的自发清除。分子生物学技术在检测总的和耐抗生素的 方面的敏感性似乎优于普通细菌培养。未来的研究应集中在寻找新方法,以有效地重建和/或维持肿瘤患者中严格厌氧的微生物群。

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