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Temozolomide-Induced Changes in Gut Microbial Composition in a Mouse Model of Brain Glioma
Xiao-Chong Li1, Bang-Sheng Wu1,2, Yi Jiang1,2
1Department of Neurosurgery, Zhongnan Hospital, Wuhan University, Wuhan, 430071, Hubei, People's Republic of China.
Background:
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.
Methods:
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.
Results:
Nineteen genera were altered during glioma progression with the most dramatic changes in Firmicutes and Bacteroidetes phyla. During glioma growth, Lactobacillus abundance decreased in the early stage (T1) and then gradually increased (T2, T3); Intestinimonas abundance exhibited a persistent increase; Anaerotruncus showed a transient increase (T2) and then a subsequent decrease (T3). Similar longitudinal changes in Intestinimonas and Anaerotruncus abundance were observed in TMZ-treated mice, but the decrease of Anaerotruncus at T3 in the TMZ-treated group was less than that in the vehicle-treated group. No significant change in Lactobacillus was observed after TMZ treatment. Additionally, compared to vehicle control, TMZ treatment led to an enrichment in Akkermansia and Bifidobacterium.
Conclusion:
Glioma development and progression altered the composition of gut microbiota. Induction of Akkermansia and Bifidobacterium as well as the prevention of the reduction in Anaerotruncus 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.
Insights
Brain tumor growth and temozolomide (TMZ) treatment significantly alter gut microbiota composition. Specific microbial changes, including increased Akkermansia and Bifidobacterium, may contribute to TMZ's anti-tumor effects.
Area of Science:
- Microbiology
- Oncology
- Gastroenterology
Background:
- Gut microbiota plays a role in brain tumor progression.
- Alterations in gut microbiota during glioma growth and temozolomide (TMZ) therapy are not well understood.
Purpose of the Study:
- To investigate the changes in gut microbiota composition during glioma progression.
- To analyze the impact of TMZ therapy on gut microbiota in glioma-bearing mice.
Main Methods:
- GL261 glioma cells were implanted in C57BL/6 mice.
- TMZ or vehicle was administered via gavage.
- Fecal samples were collected longitudinally and analyzed using 16S ribosomal DNA sequencing.
Main Results:
- Glioma progression altered gut microbiota, with significant changes in Firmicutes and Bacteroidetes phyla.
- Specific genera like Lactobacillus, Intestinimonas, and Anaerotruncus showed dynamic changes during glioma growth.
- TMZ treatment enriched Akkermansia and Bifidobacterium and prevented a significant reduction in Anaerotruncus.
Conclusions:
- Glioma development and progression significantly impact gut microbiota composition.
- The induction of Akkermansia and Bifidobacterium, and the preservation of Anaerotruncus, may mediate the anti-tumor effects of TMZ.
- This study highlights the link between specific gut microbial species and TMZ's efficacy.
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