Discovery of microbial genes could mean better gut health – sciencedaily

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As the owner of a human body, you carry billions of germs with you wherever you go. These microscopic organisms don’t just hitchhike; many of them perform essential chemical reactions that regulate everything from our digestion to our immune system to our moods.

An important set of reactions concerns the absorption of fat via bile acids. Our livers produce these acids to help digest fats and fat soluble vitamins as they travel through the small intestine. Towards the end of the small intestine, microbes convert acids into new forms, which can be beneficial or harmful.

New research from the University of Illinois identifies the latest in a set of microbial genes involved in these conversions.

“The localization of these bacterial genes will allow mechanistic studies to determine the effect of bile acid conversion on the health of the host. If we find this to be a beneficial reaction, therapeutic strategies may be possible. be developed to encourage the production of these bile acids in the gastrointestinal tract, “says Jason Ridlon, associate professor in the Department of Animal Sciences at U of I and corresponding author of a new article in Intestinal microbes.

Microbes produce enzymes that reverse the orientation of three hydroxyl groups on bile acid molecules. Reversing them in different configurations rearranges the acid molecules into forms that can be harmful or beneficial. Ridlon and other scientists had previously identified the genes for two of these enzymes, but one was still unknown.

To find the missing gene, Ridlon and colleagues looked back. Previous research associates the flipping of a specific hydroxyl group – one attached to a location on the acid molecule known as carbon-12 – with a microbe called Clostridium paraputrificum.

“We knew from the literature published a few decades ago in which species this function was reported. We confirmed it in a strain of Clostridium paraputrificum that we have in our culture collection. This function is known to be catalyzed by certain enzymes known as reductases, ”Ridlon says.

“Using the genomic sequence of Clostridium paraputrificum, we identified all candidate reductases, modified genes in E. coli and determined which reductase was able to reverse the polar group on bile acids,” he adds.

The research team then looked for similar sequences in the human microbiome.

“We were able to identify the gene in many bacterial species that were previously unknown to have this function of metabolizing bile acid. This is useful for human microbiome researchers, as the field is attempting to link function to disease. Now we know the precise DNA sequences that code for an enzyme that returns carbon-12 from bile acids, ”explains Ridlon.

Researchers have yet to determine whether reversing the hydroxyl group to carbon 12 is a good or bad thing. In the “good” category, the flip may play a role in detoxifying harmful bile acids such as deoxycholic acid (DCA) and lithocholic acid (LCA), chemicals known to damage DNA and cause blood loss. cancers of the colon, liver and esophagus. But Ridlon notes that the “good versus bad” framing oversimplifies reality.

“Although we tend to think of DCA and ACV as ‘bad’ context is very important. Clostridium difficile infection (C. diff) appears to be correlated with low levels of DCA and ACV, for example, so these bile acids appear to be protective in preventing unwanted colonizers. However, the chronic high levels of DCA and ACL due to the Western lifestyle are ‘bad’, so it’s a balancing act, ”he says. “A major goal of this research is to try to establish and maintain a ‘Goldilocks’ zone of bile acids – neither too much nor too little.”

While there is still more to learn, Ridlon says that identifying and characterizing these new microbial genes responsible for bile acid conversion is a major step forward for gut health.

The Department of Animal Sciences is part of the College of Agricultural, Consumer, and Environmental Sciences at the University of Illinois.



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