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Gut microbes, key guests on Turkey Day, could be used therapeutically

This Thanksgiving, give thanks to the millions of microbes roaming around in your gut. As you lean back from the table, your tummy content, they'll be busy breaking down the mashed potatoes, roasted vegetables, and crispy-skinned turkey.

The gut bacterium Clostridium sporogenes works overtime on Turkey Day processing the amino acid tryptophan, found in abundance in a certain festive foul. The molecules produced in the breakdown process are sent out into the bloodstream. Along the way, they affect the immune system and the biology of the intestines — like a prescription drug.

After studying this process in mice, Stanford researchers Justin Sonnenburg, PhD, and Michael Fischbach, PhD, think gut microbes might offer a new way to treat disease. Their research was published in Nature.

Studies have shown that the gut microbiome is involved with many health problems and changing its composition can affect people’s risk for disease. Knowing C. sporogenes is one of the few bacteria to break down tryptophan, the researchers wanted to study how it does this, what molecules it produces and how they affect the body at large.

The microbe produces a molecule called indolepropionic acid (IPA) from tryptophan, along with 11 other metabolites. According to the paper’s press release, the researchers found that IPA activates a specific branch of the immune system when present:

Finally, they looked at how altering the levels of IPA affected the mice. Mice with undetectable IPA, they found, had higher levels of immune cells, including neutrophils, classical monocytes and memory T cells. This suggested activation of two branches of the immune system — the innate and adaptive immune system. In addition, the mice with the engineered version of C. sporogenes had more permeable intestines, a defect which is often seen in gut diseases, including inflammatory bowel disease.

If the results hold true in humans, said Sonnenburg, it could point toward a new paradigm for treating some diseases: rather than give a compound, such as IPA, physicians may one day be able to tweak levels of bacteria to affect levels of metabolites. For instance, it might be possible to treat inflammatory bowel disease by boosting levels of C. sporogenes and ensuring patients eat enough tryptophan.

Studies like this show the potential to help the body treat itself. By taking advantage of hard working gut microbes, C. sporogenes being just one of thousands, doctors may be able to side-step the use of prescription drugs.

“While providing a stunning example of how a single gut microbe, and a single gene within that microbe, can impact host health, IPA is just the tip of the iceberg,” said Fischbach. “The possibility to positively impact human health through microbiome-produced chemicals is tremendous, and we are poised to take big strides and make this a reality.”

Previously: Hunter-gatherers' seasonal gut-microbe diversity loss echoes our permanent one, study shows, To debug your gut (and maybe your brain, too), make nice to the bugs that live inside it and Stanford researchers use color-coding to pinpoint locations of gut-bacterial strains  
Image by Argonne National Laboratory

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