Abstract / Summary
Background: Glioblastoma, isocitrate dehydrogenase wildtype, central nervous system World Health Organization grade 4, is the most common primary malignant brain tumor in adults and remains associated with poor prognosis despite aggressive multimodal treatment. The gut-brain axis has been proposed as a modulator of glioblastoma biology, but human data are scarce and the gut mycobiome has not been characterized in these patients. We characterized both bacteria and fungi at diagnosis as well as the intratumoral myeloid compartment and survival. Methods: In a prospective case-control study, we sequenced bacterial (16S rRNA gene) and fungal (internal transcribed spacer, ITS) communities from rectal swabs of 23 patients with newly diagnosed glioblastoma and 23 healthy controls. Additionally, we quantified the intratumoral myeloid compartment by immunofluorescence and performed survival analysis. Results: Both bacterial and fungal communities were more diverse in patients than in controls (Shannon, 16S p < 0.001; ITS p = 0.004), and even more diverse in patients with shorter survival. Community structure itself was unchanged, locating the difference at the level of individual taxa. Fourteen of 218 bacterial and archaeal taxa and four of 102 fungal species differed at nominal, uncorrected p [≤] 0.05. Members of the Lachnospiraceae and Ruminococcaceae were reduced in glioblastoma patients, while the methanogenic archaeon Methanobrevibacter and Nakaseomyces glabratus (formerly Candida glabrata) were enriched. Survival was also addressed at the tissue level. In the tumor, a higher density of ionized calcium-binding adapter molecule 1-positive myeloid cells was associated with longer survival, independently of age, performance status and extent of resection (hazard ratio 0.82 per percentage point, 95% confidence interval 0.67-0.99). Conclusions: This study characterizes the gut bacteriome and mycobiome of newly diagnosed glioblastoma patients and identifies candidate taxa, among them several butyrate- and propionate producers within the depleted Lachnospiraceae and Ruminococcaceae. Combining these observations with the established role of short-chain fatty acids in microglial maturation, we hypothesize that the myeloid compartment is the interface at which the gut-level and tissue-level findings converge.