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Scientists have discovered a connection between bacteria in the gut and antitumor immune responses in the liver, bacteria found in the gut of mice affect the liver’s antitumor immune function. Microbiome is the collection of bacteria and other microorganisms that live in or on the body.
In humans, the greatest proportion of the body’s total microbiome is in the gut. To investigate whether gut bacteria affect the development of tumors in the liver, Dr. Greten and his team carried out a series of experiments with mice. They used three mouse liver cancer models, and found that when they depleted gut bacteria using an antibiotic “cocktail,” the mice that had the antibiotics developed fewer and smaller liver tumors and had reduced metastasis to the liver.
The investigators next studied the immune cells in the liver to understand how the depletion of gut bacteria suppressed tumor growth in the liver of the antibiotic-treated mice. Antibiotic treatment increased the numbers of a type of immune cell called NKT cells in the livers of the mice. Further experiments showed that, in all three mouse models, the reduction in liver tumor growth that resulted from antibiotic treatment was dependent on these NKT cells.
Next, they found that the accumulation of the NKT cells in the liver resulted from an increase in the expression of a protein called CXCL16 on cells that line the inside of capillaries in the liver. Mice treated with antibiotics have more CXCL16 production in endothelial cells because bile acids can control the expression of CXCL16. Treating mice with bile acids can actually change the number of NKT cells in the liver, and thereby the number of tumors in the liver.
Bile acids are formed in the liver and break down fats during digestion. Bacterial species- Clostridium scindens, controls metabolism of bile acids in the mouse gut, CXCL16 expression, NKT cell accumulation, and tumor growth in the liver. Bile acids control the expression of the CXCL16 protein in the liver of humans.
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