Table 2.

Effects of gut microbiota-metabolites on glioma.

Gut microbiota- metabolites	Mainly involved immune cells or substances	Findings	References
Tryptophan metabolites	T cells/DCs/TAMs antigenpresenting cells (APCs)/astrocytes/microglia	Activating the AHR pathway triggering tumor cell proliferation in astrocytoma, medulloblastoma, and glioblastoma (GBM).	(34)
Arginine metabolites	polyamines and nitric oxide	Polyamine may induce tumor cell proliferation and metastasis by up-regulating the expression of ornithine decarboxylase, spermidine, and spermine acetyltransferase, and Akt1. Nitric oxide can interfere with T cell function by inducing T cell apoptosis. Arginine depletion in GBM can induce excessive autophagy, which will be toxic to tumor cells and may induce apoptosis.	(35–40)
Glutamate metabolites	αKG	Gut microbiome can influence αKG levels through Glu, and changes in αKG affect DNA methylation.	(41)
Glutamine	glutamine	Glioma growth and metabolism are highly dependent on Glutamine and Glutamine starvation therapy has also been shown to reduce the proliferation activity of GBM cells. Changes in the gut microbiome also directly or indirectly alter the content of glutamine in the brain through a variety of pathways, thereby affecting the energy supply of gliomas.	(41–45)
Short-chain fatty acids	acetate, propionate, and butyrate	The imbalance of the gut microbiome, the decrease of the proportion of probiotics, and the lack of abundance of the gut microbiome will lead to the decrease of the concentration of SCFAs in circulation, resulting in the disturbance of morphology and function of microglial cells, resulting in chronic stress status, which affects the development and prognosis of tumors through stress-related pathways. Butyrate affects the immune system by inducing Treg differentiation and regulating inflammation. Acetate and glucose participate in the TCA cycle together, affecting the production of acetyl-CoA in GBM and Acetylation of Rictor by acetyl-CoA actives mTORC2 drives the proliferation and survival of GBM.	(46–49)