Green George B H, Cox-Holmes Alexis N, Backan Olivia, Valbak Olivia, Potier Anna Claire E, Chen Dongquan, Morrow Casey D, Willey Christopher D, McFarland Braden C
Department of Cell, Developmental and Integrative Biology, Birmingham, AL 35294, USA.
Undergraduate Cancer Biology Program, Birmingham, AL 35294, USA.
Microorganisms. 2024 May 17;12(5):1015. doi: 10.3390/microorganisms12051015.
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.
除了胶质母细胞瘤的标准疗法外，患者通常还会分别服用甲氧苄啶-磺胺甲恶唑（TMP-SMX）和地塞米松来预防感染和减轻脑水肿。由于肠道微生物群会影响癌症治疗的疗效，因此了解这些药物如何影响患者的肠道微生物群非常重要。本研究使用已植入人类微生物群的小鼠，旨在研究TMP-SMX和地塞米松如何影响肠道微生物组。将两株人源化微生物群（HuM）Rag1小鼠，即HuM1Rag和HuM2Rag，每天通过口服灌胃给予TMP-SMX或地塞米松，持续一周。在治疗前（治疗前）、治疗开始后一周（治疗后1周）和治疗后三周（治疗后3周）收集粪便样本，并使用16S rRNA测序分析细菌DNA。用TMP-SMX治疗的HuM1Rag小鼠在所有时间点的α多样性、β多样性和功能途径都有显著变化，而在HuM2Rag小鼠中，微生物组的变化最小。同样，地塞米松治疗导致HuM1Rag小鼠的微生物组发生显著变化，而HuM2Rag小鼠的微生物组大多未受影响。我们的研究结果表明，胶质母细胞瘤治疗期间使用的常规药物会扰乱肠道微生物群，某些微生物组组成比其他微生物组更敏感，并且这些治疗可能会影响标准治疗的整体疗效。
