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| Current research has shed light on the effects of the gut microbiome and diet on liver health in humans. McMurrayJulie/Pixabay |
The liver, being closely connected to the gut, is the first recipient of the gut's microbiome.
By Patrick James Hibbert
24 Mar 2020
It defends the human host against pathogens and maintains metabolic homeostasis in addition to immune balance. Although the gut microbiome directly benefits the host, it is also involved in the development of diseases.
Recent research has revealed the carcinogenic effects of some of the small molecules produced by the gut microbiome that down-regulate the immune system in the liver. These molecules include lipopolysaccharides, bile acids, and lipoteichoic acid.
Secondary bile acids are products of the bacterial metabolism of primary bile acids which are synthesized by the liver. Secondary bile acids promote obesity-associated liver cancer through suppression of antitumor immunity. They also inactivate liver sinusoidal endothelial cells and reduce the accumulation of natural killer T-cells, which combat liver cancer.
In fact, there is mounting evidence of its contribution to both local and distant carcinogenesis in humans and animals. Known cancer-causing gut bacteria include Helicobacter Pylor and E. Coli. The liver is the first recipient of the gut’s microbiome metabolites and antigens. This is so because of its close connection through the hepatic portal vein.
Liver cancer is the most common primary hepatic malignancy and a leading cause of death in patients with cirrhosis.
Recent research has revealed the carcinogenic effects of some of the small molecules produced by the gut microbiome that down-regulate the immune system in the liver. These molecules include lipopolysaccharides, bile acids, and lipoteichoic acid.
Lipopolysaccharides can activate toll-like receptor 4, a transmembrane protein, to contribute to the pathogenesis of liver cancer. Bile acids were implicated as carcinogens as early as 1940. High levels of secondary bile acids were shown to generate reactive oxygen and nitrogen species, disrupt cell membranes and mitochondria. And they induce DNA damage and apoptosis, ultimately leading to colon cancer.
Secondary bile acids are products of the bacterial metabolism of primary bile acids which are synthesized by the liver. Secondary bile acids promote obesity-associated liver cancer through suppression of antitumor immunity. They also inactivate liver sinusoidal endothelial cells and reduce the accumulation of natural killer T-cells, which combat liver cancer.
A recent study showed that feeding toll-like receptor 5-deficient mice (T5KO mice) a diet enriched with soluble fiber, which is one that includes inulin, pectin, and fructooligosaccharides, resulted in the induction of cholestatic liver cancer. The mice with liver cancer demonstrated pre-existing microbiota dysbiosis, indicating that the induced liver cancer was microbiome-dependent.
The accumulation of fiber-fermenting bacteria and proteobacteria was also observed in the gut of T5KO mice. The fiber-fermenting bacteria included members of Clostridia, especially the Clostridium cluster XIVa, which are capable of enzymatically converting primary bile acids to secondary bile acids.
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| Some bacteria can convert primary bile acids to carcinogenic secondary bile acids. James Archer/CDC |
Recent studies imply that the liver cancer-promoting effect of clostridia, which can be enriched in the gut of T5KO mice by fiber-enriched, compositionally defined, diets are conditioned and may be related to gut microbial imbalance. In addition, significantly increased amounts of Clostridium cluster XI were found in the fecal bacterial community of mice fed a high-fat diet compared to mice fed a normal diet.
Also, refined soluble fibers have been found to induce liver cancer in T5KO mice with gut microbial imbalances while dietary intervention with insoluble fiber (cellulose) has been shown to protect T5KO mice from soluble fiber–induced liver cancer. These studies suggest a high-fat diet synergizes with the Clostridium species to promote liver cancer in mice. And, as our current understanding of cancer is, in humans too.
Also, refined soluble fibers have been found to induce liver cancer in T5KO mice with gut microbial imbalances while dietary intervention with insoluble fiber (cellulose) has been shown to protect T5KO mice from soluble fiber–induced liver cancer. These studies suggest a high-fat diet synergizes with the Clostridium species to promote liver cancer in mice. And, as our current understanding of cancer is, in humans too.
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