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.
Keywords: glioma, gut microbiota, temozolomide, tumor microenvironment, epigenetics