Department of Neurosurgery, Zhongnan Hospital, Wuhan University, Wuhan, 430071, Hubei, People's Republic of China.
Second Clinical School, Wuhan University, Wuhan, 430071, Hubei, People's Republic of China.
Drug Des Devel Ther. 2021 Apr 21;15:1641-1652. doi: 10.2147/DDDT.S298261. eCollection 2021.
Gut microbiota is associated with the progression of brain tumors. However, the alterations in gut microbiota observed during glioma growth and temozolomide (TMZ) therapy remain poorly understood.
C57BL/6 male mice were implanted with GL261 glioma cells. TMZ/sodium carboxymethyl cellulose (SCC) was administered through gavage for five consecutive days (from 8 to 12 days after implantation). Fecal samples were collected before (T0) and on days 7 (T1), 14 (T2), and 28 (T3) after implantation. The gut microbiota was analyzed using 16S ribosomal DNA sequencing followed by absolute and relative quantitation analyses.
Nineteen genera were altered during glioma progression with the most dramatic changes in Firmicutes and Bacteroidetes phyla. During glioma growth, abundance decreased in the early stage (T1) and then gradually increased (T2, T3); abundance exhibited a persistent increase; showed a transient increase (T2) and then a subsequent decrease (T3). Similar longitudinal changes in and abundance were observed in TMZ-treated mice, but the decrease of at T3 in the TMZ-treated group was less than that in the vehicle-treated group. No significant change in was observed after TMZ treatment. Additionally, compared to vehicle control, TMZ treatment led to an enrichment in and .
Glioma development and progression altered the composition of gut microbiota. Induction of and as well as the prevention of the reduction in may contribute to the anti-tumor effect of TMZ. This study helps to reveal the association between levels of specific microbial species in the gut and the anti-tumor effect of TMZ.
肠道微生物群与脑瘤的进展有关。然而，在神经胶质瘤生长和替莫唑胺（TMZ）治疗过程中观察到的肠道微生物群的改变仍知之甚少。
将 C57BL/6 雄性小鼠植入 GL261 神经胶质瘤细胞。TMZ/羧甲基纤维素钠（SCC）通过灌胃连续给药 5 天（植入后 8-12 天）。在植入前（T0）和植入后第 7 天（T1）、第 14 天（T2）和第 28 天（T3）收集粪便样本。使用 16S 核糖体 DNA 测序分析肠道微生物群，然后进行绝对和相对定量分析。
在神经胶质瘤进展过程中，有 19 个属发生改变，厚壁菌门和拟杆菌门的变化最为明显。在神经胶质瘤生长过程中，丰度在早期（T1）下降，然后逐渐增加（T2、T3）；丰度持续增加；表现出短暂增加（T2），然后随后减少（T3）。在 TMZ 治疗的小鼠中也观察到 和 丰度的相似纵向变化，但 TMZ 治疗组在 T3 时 的减少量小于载体治疗组。TMZ 治疗后 的丰度没有明显变化。此外，与载体对照组相比，TMZ 治疗导致 和 的丰度增加。
神经胶质瘤的发生和发展改变了肠道微生物群的组成。诱导 和 以及预防 的减少可能有助于 TMZ 的抗肿瘤作用。本研究有助于揭示肠道中特定微生物种类的水平与 TMZ 抗肿瘤作用之间的关联。
