Exploring Gut Microbiota Alterations with Trimethoprim-Sulfamethoxazole and Dexamethasone in a Humanized Microbiome Mouse Model

被引:2
作者
Green, George B. H. [1 ]
Cox-Holmes, Alexis N. [1 ]
Backan, Olivia [1 ,2 ]
Valbak, Olivia [1 ,2 ]
Potier, Anna Claire E. [1 ,2 ]
Chen, Dongquan [3 ]
Morrow, Casey D. [1 ]
Willey, Christopher D. [4 ]
McFarland, Braden C. [1 ]
机构
[1] Dept Cell Dev & Integrat Biol, Birmingham, AL 35294 USA
[2] Undergrad Canc Biol Program, Birmingham, AL 35294 USA
[3] Dept Genet, Birmingham, AL 35294 USA
[4] Univ Alabama Birmingham, Heersink Sch Med, Dept Radiat Oncol, Birmingham, AL 35233 USA
关键词
microbiome; trimethoprim; sulfamethoxazole; dexamethasone; glioblastoma; HIGH-GRADE GLIOMAS; BILE-ACIDS; CORTICOSTEROIDS; GLIOBLASTOMA; METABOLITES; RESISTANCE;
D O I
10.3390/microorganisms12051015
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Along with the standard therapies for glioblastoma, patients are commonly prescribed trimethoprim-sulfamethoxazole (TMP-SMX) and dexamethasone for preventing infections and reducing cerebral edema, respectively. Because the gut microbiota impacts the efficacy of cancer therapies, it is important to understand how these medications impact the gut microbiota of patients. Using mice that have been colonized with human microbiota, this study sought to examine how TMP-SMX and dexamethasone affect the gut microbiome. Two lines of humanized microbiota (HuM) Rag1-/- mice, HuM1Rag and HuM2Rag, were treated with either TMP-SMX or dexamethasone via oral gavage once a day for a week. Fecal samples were collected pre-treatment (pre-txt), one week after treatment initiation (1 wk post txt), and three weeks post-treatment (3 wk post txt), and bacterial DNA was analyzed using 16S rRNA-sequencing. The HuM1Rag mice treated with TMP-SMX had significant shifts in alpha diversity, beta diversity, and functional pathways at all time points, whereas in the HuM2Rag mice, it resulted in minimal changes in the microbiome. Likewise, dexamethasone treatment resulted in significant changes in the microbiome of the HuM1Rag mice, whereas the microbiome of the HuM2Rag mice was mostly unaffected. The results of our study show that routine medications used during glioblastoma treatment can perturb gut microbiota, with some microbiome compositions being more sensitive than others, and these treatments could potentially affect the overall efficacy of standard-of-care therapy.
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页数:22
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