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

• Published in: Biomedicines Vol. 12; no. 7; p. 1566
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 15-07-2024
• Subjects: allogeneic; Allografts; Antibiotic resistance; Antibiotics; Bacteria; Bacteriology; Biodiversity; Carbapenemase; Carbapenems; Cephalosporins; changes; DNA sequencing; Feces; Firmicutes; Fluoroquinolones; Genes; Graft versus host disease; Gram-negative bacteria; gut microbiome; Hematology; hematopoietic stem cell transplantation; Hematopoietic stem cells; Intestinal microflora; Klebsiella; Leukemia; Mass spectrometry; Microbiota; Mortality; Scientific imaging; Shigella; Software; Stem cell transplantation; Test systems; time-dependent; France; United States > US; Russia; Bacillota; carbapenem resistant; CHROMagar technique; changes; gut microbiome; Klebsiella pneumoniae colonization; NDM; allogeneic; ESBL; hematopoietic stem cell transplantation; time-dependent; MDR; NGS; antibiotic resistance genes; OXA-48; DNA sequencing; Enterobacteriaceae; KPC
• ISSN: 2227-9059; 2227-9059
• DOI: 10.3390/biomedicines12071566

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.