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Microbiota Analysis Using Two-step PCR and Next-generation 16S rRNA Gene Sequencing
Published on: October 15, 2019
Specific Intratumoral Microbiome Signatures in Human Glioblastoma and Meningioma: Evidence for a Gut-Brain Microbial
Dalila Mehelleb1,2, Abderezak Ghidouche1,3, Simone Baldi4
1University of Bejaia, Faculty of Natural and Life Sciences, Bejaia 06000, Algeria.
Abstract:
Brain tumors (BTs), including glioblastoma (GBM) and meningioma (MGM), contribute significantly to the global cancer burden. The microbiome has been implicated in carcinogenesis, yet its role in BTs remains underexplored. We performed 16S rRNA gene sequencing of the gut microbiota (GM) and intratumoral microbiome (ItM) from fresh tissue samples of 9 patients with GBM and 18 with MGM. 12 age- and sex-matched healthy controls (HCs) were also enrolled. GM profiling revealed reduced alpha diversity and distinct microbial communities in BT patients versus HCs. Notably, Verrucomicrobiota and Synergistaceae were enriched, while Lachnospiraceae, Peptostreptococcaceae, and Muribacter spp. were depleted. GBM patients showed reductions in Peptostreptococcaceae and the Eubacterium hallii group, while MGM patients had increased Synergistia and Erysipelatoclostridium. Compared with MGM, GBM patients were enriched in Peptostreptococcales-Tissierellales, Coprobacillus, and Peptoniphilus but depleted in Weissella. Venn analysis revealed 176 genera shared across groups with unique taxa distinguishing tumor patients and HCs. ItM profiling revealed enrichment of Proteobacteria, Actinomycetota, and Campylobacterota in GBM, while MGM contained higher levels of Bacillota and Bacteroidota. GBM tissues harbored Burkholderia-Caballeronia-Paraburkholderia, Helicobacter, and Leifsonia, whereas MGM tissues were dominated by Bacteroides and Blautia. Notably, stool and tumor samples shared 91 genera in GBM and 105 in MGM. This study provides novel insights by (i) characterizing ItM from fresh samples, (ii) comparing ItM profiles of GBM and MGM, (iii) linking GM and ItM within the same patients, and (iv) suggesting potential clinical implications for BT management.
Insights
The gut and tumor microbiomes differ between brain tumor patients and healthy individuals. Specific bacteria are altered in glioblastoma and meningioma, suggesting potential roles in brain tumor development and management.
Area of Science:
- Microbiology
- Oncology
- Genomics
Background:
- Brain tumors (BTs), including glioblastoma (GBM) and meningioma (MGM), represent a significant global health challenge.
- The gut microbiome's influence on cancer is recognized, but its specific role in BTs is largely unexplored.
- Understanding the intratumoral microbiome (ItM) is crucial for elucidating BT pathogenesis.
Purpose of the Study:
- To characterize the gut microbiota (GM) and ItM in patients with GBM and MGM.
- To compare microbial profiles between BT patients and healthy controls (HCs).
- To investigate the relationship between GM and ItM and its potential clinical implications for BT management.
Main Methods:
- 16S rRNA gene sequencing was employed to analyze the GM and ItM from fresh tissue samples.
- Samples were collected from 9 GBM patients, 18 MGM patients, and 12 age- and sex-matched HCs.
- Bioinformatic analyses included diversity assessments, differential abundance testing, and Venn analyses.
Main Results:
- BT patients exhibited reduced GM alpha diversity and distinct microbial communities compared to HCs, with notable enrichment of Verrucomicrobiota and Synergistaceae, and depletion of Lachnospiraceae and Peptostreptococcaceae.
- GBM and MGM showed specific GM alterations: GBM patients had reduced Peptostreptococcaceae and Eubacterium hallii group, while MGM patients had increased Synergistia and Erysipelatoclostridium.
- ItM profiling revealed distinct compositions: GBM tissues were enriched in Proteobacteria, Actinomycetota, and Campylobacterota, harboring Burkholderia-Caballeronia-Paraburkholderia, Helicobacter, and Leifsonia.
- MGM tissues showed higher levels of Bacillota and Bacteroidota, dominated by Bacteroides and Blautia.
- Significant overlap was observed between GM and ItM in both GBM (91 genera) and MGM (105 genera).
Conclusions:
- The gut and intratumoral microbiomes are significantly altered in brain tumor patients.
- Distinct microbial signatures differentiate GBM from MGM, and from healthy controls.
- The shared microbial genera between gut and tumor suggest a potential link influencing BT development and offering avenues for novel therapeutic strategies.
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