TABLE 1.

Some important factors in cancer that are affected by gut microbiota.

Factor	A1	Presence of gut microbiota			References
		Genus/Strain	B2	Modulatory Mechanisms
GM-CSF	D3	Lactobacillus reuteri, Enterococcus faecalis, Lactobacillus crispatus and Clostridium orbiscindens	P4	Reduced expansion and activation of MDSCs by IL-17A-induced release of GM-CSF	Menetrier-Caux et al., 1998; Brown et al., 2017
IL-4	I5	Lactobacillus spp.	P	Reduced suppressive activity of MDSCs on anti-tumor T-cells by decreasing the expression of IL-4 and IL-13 and subsequent downregulation of arginase 1 expression	Rutschman et al., 2001; Bronte et al., 2003; Johansson et al., 2012
Arginine availability	−	Diverse	P	-Reduced availability of arginine through the depletion of dietary arginine in gut. -Increased radio sensitization of arginine-depleted cancer cells. -More efficient arginine deprivation therapy. -Induced autophagy and apoptosis in arginine auxotrophic cancer cells.	Syed et al., 2013; Hinrichs et al., 2018; Zou et al., 2019
Arginine and endogenous nitric oxide availability	−	Prevotella spp.	P	-Reduced availability of arginine and its lower subsequent conversion into nitric oxide. -Improved activity of anti-tumor T-cell by inhibiting MSDCs expansion.	Dai et al., 2015; Kao et al., 2015
Nitric oxide	−	−	P	-Conversion of dietary arginine into nitric oxide. -Increased permeability of mitochondrial membrane and subsequent promoted release of cytochrome c, expression of apoptosis inducing factor, and activation of certain caspases at high level of nitric oxide. -Nitric oxide-induced DNA damage and cell death in cancer cells. -Increased sensitization of resistant tumor cells to apoptosis during chemo-immunotherapy in the presence of nitric oxide.	Sarti et al., 2012; Bonavida and Garban, 2015; Chang et al., 2015; Tengan and Moraes, 2017
			N6	-Conversion of dietary arginine into nitric oxide. -Increased MSDCs expansion and subsequent decreased activity of anti-tumor T-cells.
Peroxynitrite	I	−	N	-Conversion of dietary arginine into nitric oxide and the subsequent formation of peroxynitrite upon reaction with superoxide radicals. -Increased MSDCs-mediated suppressive activity on T-cells. -Promoted tumor progressions by rendering T-cell unresponsive due to aberrant nitration of the T-cell receptor and CD8+ molecules in the presence of excessive amounts of peroxynitrite.	Nagaraj et al., 2007; Gabrilovich and Nagaraj, 2009 Bentz et al., 2000; Cobbs et al., 2003; Gabrilovich and Nagaraj, 2009
Polyamines availability	−	−	N	Conversion of arginine into polyamines which may induce the proliferation and metastasis of tumor cells.	Dai et al., 2017; Zou et al., 2019
Antioxidants	−	Diverse	P	-Reduced suppressive activity of MDSCs on anti-tumor T-cells by some microbial metabolites such as vitamins, antioxidants, and polyphenols that scavenge ROS.	Dehhaghi et al., 2018a, 2019a
Tryptophan availability	−	Burkholderia, Ralstonia, Klebsiella, Citrobacter, and Bifidobacterium infantis	N	-Assimilation of dietary tryptophan which causes an aberrant proliferation and functions of effector T-cells due to the inhibition of fatty acid synthesis in human primary CD4+ T-cells by overactivating GGN2 -Induced tumor immunoresistance and survivability by the phosphorylation of eukaryotic initiation factor 2α	Ye et al., 2010; Eleftheriadis et al., 2015; Schalper et al., 2017; Kaur et al., 2019
IDO-1 IFN-γ	I	−	N	-Overactivation of AhR by tryptophan-derived metabolites of gut microbiota (e.g., kynurenine, kynurenic acid) -Ligand-activated AhR eventually increases IDO-1 by increasing the release of IL-6 and IFN-γ.	Glauben et al., 2006; DiNatale et al., 2010; Litzenburger et al., 2014; Wang et al., 2014; Dehhaghi et al., 2018a, 2019a; Martin-Gallausiaux et al., 2018; Kaur et al., 2019
			P	-Inhibited IFN-γ and IDO-1 expression by microbial SCFAs through their downregulatory effects on STAT1 and histone deacetylase
IDO-1	I	−	N	-Increased pathogenesis of gliomas by overactivating IDO-1 through the production of inflammatory cytokines, amyloid peptide, and lipopolysaccharides. -IDO-1-suppressed expansions of T-cells and other immune cells via tryptophan depletion route (see above)	−
IFN-γ	I	−	N	-Weak determinant for impacting T-cell suppressive potency, accumulation, or phenotype of MDSCs − Increases cancer pathogenesis through modification of kynurenine pathway at IDO-1 step (see above).	−
Microglia dysbiosis	I	Diverse for example Clostridium spp.	N	-Microbial SCFAs induce the release of TGF-β that triggers dysbiosis of Th1 and Th2 in favor of microglia M2c phenotype and inhibits cytokine production, lymphocyte proliferation, and T cell differentiation.	Mantovani et al., 2004; Heijtz et al., 2011; Erny et al., 2015; Bauché and Marie, 2017; Dehhaghi et al., 2018a, 2019a,b; Roesch et al., 2018; Mehrian-Shai et al., 2019
		−	N	Induced MDSCs suppressive activity on anti-tumor T-cells due to a higher production of ROS in the brain by activated and inflamed microglia in response to microbiota-derived neurotoxic substances or metabolites (e.g., amyloid proteins and LPS)

¹Anti-cancer impact by gut microbiota.

² Effect on the brain cancer development.

³Decreased.

⁴Increased.

⁵Positive.

⁶Negative.