Antibiotics treatment promotes vasculogenesis in the brain of glioma-bearing mice.
Maria RositoJaveria MaqboolAlice ReccagniOttavia GiampaoliFabio SciubbaFabrizio AntonangeliFerdinando ScavizziMarcello RaspaFederica CordellaLucrezia TondoSilvia Di AngelantonioFlavia TrettelAlfredo MiccheliGiuseppina D'AlessandroCristina LimatolaPublished in: Cell death & disease (2024)
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.
Keyphrases
- resting state
- induced apoptosis
- cerebral ischemia
- white matter
- mouse model
- functional connectivity
- stem cells
- cell cycle arrest
- high glucose
- diabetic rats
- oxidative stress
- epithelial mesenchymal transition
- signaling pathway
- inflammatory response
- drug induced
- metabolic syndrome
- brain injury
- blood brain barrier
- replacement therapy
- pi k akt