Home Medizin Die Tryptophan-Verdauung durch das Darmmikrobiom begünstigt Arthritis-Entzündungen

Die Tryptophan-Verdauung durch das Darmmikrobiom begünstigt Arthritis-Entzündungen

von NFI Redaktion


A faculty member of the University of Colorado School of Medicine says she and her colleagues have discovered how bacteria in the digestive system can break down tryptophan in food into an inflammatory chemical that primes the immune system for arthritis.

The study was co-authored by Kristine Kuhn, MD, PhD, Scoville Endowed Chair and head of the CU Department of Rheumatology. Several of her department colleagues worked on the paper, which was published in February in the Journal of Clinical Investigation.

Tryptophan is an essential amino acid found in many protein-rich foods, including meat, fish, dairy products, as well as certain seeds and nuts. It has many uses in the body, including helping with the production of proteins, muscles, enzymes, and neurotransmitters – the chemical messengers of the nervous system. Our bodies do not create it; we obtain it through our diet.

Many people associate tryptophan as the ingredient in turkey that supposedly makes us sleepy after a Thanksgiving feast. In fact, researchers say that while tryptophan plays a role in regulating the sleep cycle, the amount found in turkey is likely not a significant cause of post-dinner drowsiness.

Cause and Effect

Kuhn and her colleagues wanted to figure out how a substance that often has a positive effect in the body is being converted into a pathway for inflammatory diseases like rheumatoid arthritis, which affects about 1% of the population. Untreated, it can lead to painful swelling in hands and feet, as well as joint deformities.

„It is known that the microbiome – the bacteria in our gut – can break down tryptophan into byproducts. Some of these byproducts have anti-inflammatory properties, but we have also linked some inflammatory causes of these products. We are the first to identify which products contribute to inflammation and how they do it.“

Kristine Kuhn, MD, PhD, Scoville Endowed Chair and head of the CU Department of Rheumatology

She says that the new research „builds upon some observations we made in patients with spondyloarthritis – not quite rheumatoid arthritis, but a closely related condition – where we found changes in the microbiome associated with increased production of these products called indoles that bacteria turn tryptophan into. Similar changes have been observed in arthritis studies with mice, she says.

„We gave mice antibiotics to wipe out their microbiome, and they did not get arthritis and had no indole,“ she says. „So we said: Okay, what if they have a microbiome and we put them on a low-tryptophan diet? The microbiome cannot break down tryptophan into indole, and the mice did not develop arthritis. So two different ways: we have shown that it is tryptophan being broken down into indole by the microbiome.“

Inflammatory Signs

How does this work? „We found that in the presence of indole, mice start to develop autoreactive T cells that are more pro-inflammatory. They have fewer of these regulatory T cells that help maintain balance in the immune system, and they begin to develop more antibodies. We found that the antibodies showed signs of being more inflammatory when indole was present.“

The paper concludes that „blocking indole formation could represent a unique therapeutic avenue“ for rheumatoid arthritis and spondyloarthritis. It’s about finding the right path for the body’s own tryptophan, says Kuhn.

„When tryptophan interacts with the cells of our body, it tends to be broken down into anti-inflammatory products, as opposed to when it interacts with bacteria cells and becomes more inflammatory. We are thinking about how this could lead to therapies: How do you preserve that? balance, so that tryptophan goes into the anti-inflammatory pathway? How can you manipulate gut bacteria to shift this balance? That’s the direction we want to go in the future.“

Does Kuhn’s research suggest that we should eat differently? „I am often asked that,“ she says. „A diet rich in plant fibers and lean meat – the whole Mediterranean diet – seems to put the microbiome in a healthier state, so you get the anti-inflammatory properties of tryptophan, while the typical Western diet seems to lean more towards the inflammatory pathway.“

As for other ways to protect against arthritis, Kuhn says that through the research of her colleagues in the Rheumatology Department, „we have begun to understand the risk stage where we can actually identify people who are likely to develop rheumatoid arthritis in the next year.“ There is some data suggesting that we could intervene during this period and prevent diseases, but we are still not quite sure how to intervene correctly.“

Source:

University of Colorado Anschutz Medical Campus

Journal Reference:

Seymour, BJ, et al. (2024). Microbiota-dependent indole production stimulates the development of collagen-induced arthritis in mice. The Journal of Clinical Investigation. doi.org/10.1172/JCI167671.

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