Antibiotics treatment promotes vasculogenesis in the brain of glioma-bearing mice

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作者
Maria Rosito
Javeria Maqbool
Alice Reccagni
Ottavia Giampaoli
Fabio Sciubba
Fabrizio Antonangeli
Ferdinando Scavizzi
Marcello Raspa
Federica Cordella
Lucrezia Tondo
Silvia Di Angelantonio
Flavia Trettel
Alfredo Miccheli
Giuseppina D’Alessandro
Cristina Limatola
机构
[1] Sapienza University,Department of Physiology and Pharmacology
[2] Center for Life Nanoscience & Neuroscience Istituto Italiano di Tecnologia@Sapienza,Department of Environmental Biology
[3] Sapienza University,NMR
[4] Sapienza University,Based Metabolomics Laboratory (NMLab)
[5] National Research Council (CNR),Institute of Molecular Biology and Pathology
[6] EMMA CNR,Department of Physiology and Pharmacology
[7] IRCCS Neuromed,undefined
[8] Sapienza University,undefined
[9] Laboratory Affiliated to Institute Pasteur Italia,undefined
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摘要
In recent years, several studies described the close relationship between the composition of gut microbiota and brain functions, highlighting the importance of gut-derived metabolites in mediating neuronal and glial cells cross-talk in physiological and pathological condition. Gut dysbiosis may affects cerebral tumors growth and progression, but the specific metabolites involved in this modulation have not been identified yet. Using a syngeneic mouse model of glioma, we have investigated the role of dysbiosis induced by the administration of non-absorbable antibiotics on mouse metabolome and on tumor microenvironment. We report that antibiotics treatment induced: (1) alteration of the gut and brain metabolome profiles; (2) modeling of tumor microenvironment toward a pro-angiogenic phenotype in which microglia and glioma cells are actively involved; (3) increased glioma stemness; (4) trans-differentiation of glioma cells into endothelial precursor cells, thus increasing vasculogenesis. We propose glycine as a metabolite that, in ABX-induced dysbiosis, shapes brain microenvironment and contributes to glioma growth and progression.
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