Role of the microbiome in non-gastrointestinal cancers

Table 1 The role of the microbiota in non-gastric cancers

Cancer	Mechanism	Ref.
Protective role
B16/F10 melanoma and LLC	Microbiota was required for the development of anti-cancer immunity	[87]
	Commensal microbiota was essential for the development and anti-cancer activity of γδ-Th17 cells
HCC	Microbiota was required for immune system development	[111]
	Commensal microbiota was needed for the development of the immune system in the liver, which enables mice to clear HBV. A chronic infection with HBV is a major risk factor for HCC
Tumor-promoting role
Skin cancer	Dysbiosis causes a cancer-stimulating inflammatory response in the host	[27]
	Microbiota-derived Flagellin stimulates TLR5-MyD88 signaling which promotes skin cancer development
Breast cancer	Upon injection of a carcinogen, GF mice showed a lower cancer burden than SPF mice	[43]
Lung	Dysbiosis causes a cancer-stimulating inflammatory response in the host	[102]
	E. coli/LPS in the lungs promotes lung injury and inflammation, which lead to an enhanced metastasis from the primary tumor to the lung
Ovarian and breast cancer	Dysbiosis inhibits anti-tumor immunity: Gut microbiota of TLR5-/- mice promoted the accumulation of MDSCs at the site of breast and ovarian cancers. MDSCs in their turn suppressed anti-cancer immunity	[44]
Breast cancer	Infection with a gastric pathogen promoted cancer-stimulating inflammatory responses	[30]
	In mice, infection with the gastric bacteria H. hepaticus led to an influx of neutrophils in the mammary gland that then promoted cancer. Treatment with antibiotics or the depletion of neutrophils significantly halted cancer development
Liver	Infection of mice prone to liver cancer with H. hepaticus led to a significant enhancement of carcinogenesis	[114]

LLC: Lewis lung carcinoma; HCC: Hepatocellular carcinoma; HBV: Hepatitis B virus; TLR: Toll-like receptor; MDSCs: Myeloid-derived suppressor cells.