Key points:
- Researchers have shown that tryptophan can prime the immune system toward arthritis.
- Experiments in mice show bacteria in the digestive system can break down tryptophan into an inflammatory chemical.
- The findings opens up new therapy avenues and targets for RA and other types of arthritis.
Many people think of tryptophan as the ingredient in turkey that makes us sleepy after a Thanksgiving feast. That’s not really true, but tryptophan is an essential amino acid humans ingest through protein-rich foods, including meats, fish, dairy products, and certain seeds and nuts. It has many positive uses in the body, including helping in the production of proteins, muscles, enzymes, and neurotransmitters.
However, researchers have now identified how the common food ingredient can take a wrong turn. They identified the means in which bacteria in the digestive system break down tryptophan into an inflammatory chemical that primes the immune system toward arthritis.
University of Colorado’s Kristine Kuhn says the new research builds upon observations her team has made in patients with spondyloarthritis. They found that changes in the microbiome were associated with increased production of products called indoles, which are what bacteria make from tryptophan.
In the new study, published in Journal of Clinical Investigation, Kohn’s team found that when indole is present, mice start to develop autoreactive T-cells that are more inflammatory. They have less regulatory T-cells that help maintain balance in the immune system, and they start to develop antibodies that are more pathogenic. The team says the antibodies had “flags” for being more inflammatory when indole was present.
“We put mice on antibiotics to wipe out their microbiome, and they didn’t get arthritis, and they didn’t have indole,” said Kuhn. “So, we said, what if they do have a microbiome and we put them on a diet with little tryptophan? The microbiome can’t break down tryptophan into indole, and the mice didn't get arthritis. So, two different ways, we showed that it’s tryptophan that’s broken down by the microbiome into indole.”
The paper concludes that “blockade of indole generation may present a unique therapeutic pathway” for rheumatoid arthritis and spondyloarthritis.
“If tryptophan hits our body’s cells, it tends to go get broken down into anti-inflammatory products versus when it hits the bacterial cells and goes more inflammatory. The ways we think about how this could lead to therapies are: How do you keep that balance tipped so that tryptophan goes toward that anti-inflammatory pathway? How can you manipulate intestinal bacteria to tip that balance? That's where we’re interested in going in the future,” said Kuhn.