Research & Development B. xylanisolvens Bacteria in the gut may be useful...

B. xylanisolvens Bacteria in the gut may be useful in NASH treatment

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Excessive smoking and nicotine patches lead to nicotine buildup in the gut. This can cause severe non-alcoholic fatty liver disease which may eventually progress into liver failure due to inflammation caused by excessive amounts of fat in the organ. The accumulation of nicotine in the guts of smokers is a leading cause of nonalcoholic steatohepatitis or NASH. 

In order to cement the relationship between NASH and nicotine, scientists extensively studied the intestinal AMP kinase alpha-1. This is sometimes known as a cellular sensor that plays a part in maintaining energy homeostasis. It was also known to interact with nicotine and experiments have revealed that nicotine triggers the activation of AMP kinase alpha-1, which in turn activates another enzyme, SMPD3 that controls the production of certain types of lipids. High levels of SMPD3 are often associated with NASH and other metabolic diseases. 

A study conducted by Frank Gonzalez, Ph.D., of the National Cancer Institute and Lulu Sun at the National Institutes of Health in Maryland found that suppressing this particular enzyme in mice who were given nicotine decelerated NASH progression.

The study was published in Nature and highlighted the mechanism through which nicotine interested compounds in the intestine and led to NASH. 

The team also demonstrated how the bacterium Bacteroides xylanisolvens is capable of breaking down nicotine particles in the guts of mice who had been fed nicotine in water. Mice who had been treated with the bacterium showed a less severe manifestation of the disease and generally had less nicotine in their guts. This is the first time that scientists have been able to identify a microbiota in the gut that is capable of breaking down nicotine.

The first step of the study was to prove that nicotine did in fact build up in the bodies of smokers and to do so researchers analyzed stool and gut lining samples from 30 smokers and 3 non-smokers and as expected smokers had higher levels of nicotine in their samples. This result was mirrored in mice when they were injected with nicotine.

In the next phase of the research, scientists tested whether or not the makeup of the gut microbiome had any impact on nicotine levels. For this purpose they fed 2 sets of mice water infused with nicotine, however, one set of mice had no bacteria in their microbiome and the other control set had a clear selection of bacterial pathogens. 

In the end, less nicotine had accumulated in the control group of mice. In order to identify what microbe had been successful in breaking down nicotine, scientists screened a genome database for bacteria with enzymes that were known to break down nicotine.

One microbe, in particular, caught scientists’ eyes, the B. xylanisolvens, which was abundant in samples with the lowest amounts of nicotine, when it was colonized in mice it broke down nicotine in vivo. Further experiments revealed that it was the NicX gene in the microbe that gave it the nicotine-degrading abilities

Sun has proposed conducting experiments to develop the NicX enzyme for use in people to counter fatty liver disease.

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