The discovery of microbial genes could mean better intestinal health


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As the owner of a human body, you carry billions of microbes with you wherever you go. These microscopic organisms are not just a problem; 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 is related to the absorption of fats by bile acids. Our livers make these acids to help digest fats and fat-soluble vitamins as they travel through the small intestine. Near 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 microbes involved in these conversions.

“Locating these bacterial genes will allow mechanistic studies to determine the effect of bile conversion on the health of the host. If we find it to be a beneficial reaction, therapeutic strategies can be developed to promote the production of these bile acids in the gastrointestinal tract, ”says Jason Ridlon, associate professor in the Department of Animal Science at U of I and corresponding author of a new article inside Intestinal microbes.

Microbes produce enzymes that reverse the orientation of three on bile acid molecules. Surrounding them in different configurations rearranges the acid molecules in ways that can be harmful or beneficial. Ridlon and other scientists had already identified the genes of two of these enzymes, but one was still unknown.

To find the missing gene, Ridlon and his collaborators looked back in time. Previous research has linked the release of a specific hydroxyl group — one attached to a location in the acid molecule known as carbon-12 — to 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 crop collection. This function is known to be catalyzed by certain enzymes. known as reductases “. Diu Ridlon.

“Using the genome sequence of Clostridium paraputrificum, we identified all candidate reductases, designed the 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 numerous bacterial species that were previously unknown to have this bile acid metabolizing function. This is useful for human microbiome researchers, as the field is moving toward the relationship of function with disease.We now know DNA precise sequences encoding an enzyme that reverses carbon-12 from bile acids, “says Ridlon.

Researchers have yet to find out whether flipping the hydroxyl group to carbon 12 is a good or bad thing. In the “good” category, flip can play a role in detoxifying harmful bile acids such as deoxycholic acid (DCA) and lithocholic acid (LCA), chemicals known to damage DNA and cause cancer. colon, liver and esophagus. But Ridlon points out that framing “good versus bad” oversimplifies reality.

“Although we tend to think that ACD and stroke are” bad, “the context is very important. Clostridium difficile infection (C. diff) appears to correlate with low levels of ACD and stroke, e.g. so these bile acids appear to be protective to prevent unwanted colonizers. Chronically high levels of ACD and LCA due to the western lifestyle are “bad,” but it is therefore an act of balance. ” , he says. “One of the main goals of this research is to try to establish and maintain a ‘Goldilocks area’ of “Not too much or too little.”

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

Lactobacillus manipulates bile acids to create a favorable intestinal environment

More information:
Heidi L. Doden et al, Completion of the intestinal microbial epi-bile acid pathway, Intestinal microbes (2021). DOI: 10.1080 / 19490976.2021.1907271

Citation: Discovery of microbial genes could mean greater intestinal health (2021, May 27) recovered May 27, 2021 at .html

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