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Amino acid promotes regression of intestinal inflammation

(Grafik: J Clin Invest. 2020. https://doi.org/10.1172/JCI126923)

Group of researchers at FAU discovers previously unknown role of L-arginine

A lack of the amino acid L-arginine leads to increased inflammation of the intestinal mucosa. This is the conclusion of research carried out by a working group led by Prof. Dr. Jochen Mattner, Professor of Molecular Microbiology and Infection Immunology at the Institute of Microbiology – Clinical Microbiology, Immunology and Hygiene at FAU. In conjunction with other clinics and institutes in Erlangen and Regensburg, the researchers investigated how the availability of individual by-products of the metabolism in the bowel can influence inflammatory reactions. They discovered that L-arginine could play an important role in the onset and development and also in the treatment of the two most common inflammatory conditions of the bowel – Crohn’s disease and ulcerative colitis. The research group has now published its results in the Journal of Clinical Investigation.

The human bowel contains up to ten times more bacteria than the number of cells in the entire human body. The interaction between these bacteria, known as intestinal microbiota, with the body’s own cells in the bowel is important for digestion and metabolism, for the blood supply to the bowel, the permeability of the vessels, and for controlling inflammation. Changes in the interaction of the microbiota with the upper layer of the intestinal wall called the intestinal epithelium, the cells on the inside walls of blood vessels and the various immune cells in the intestinal wall affect our wellbeing and our health. An imbalance in this interaction occurs in both the most common inflammatory conditions of the bowel, Crohn’s disease and ulcerative colitis. Among others, this leads to changes to the protein metabolism of the human body and to changes to the intestinal microbiota.

The current findings suggest that the amino acid L-arginine plays an important role in bowel health. It can be found in a wide variety of foods and in our bodies and it is involved in several biological functions. It serves as a joint raw material for both enzymes arginase 1 (Arg1) and inducible nitric oxide synthase 2 (NOS2), which decisively influence immune responses and often work contrary to each other. At the same time, L-arginine is considered a source of other metabolic compounds such as polyamines, which promote cell growth. The amino acid is ultimately a central by-product of the urea cycle, which is responsible for detoxifying the body.

Prof. Mattner and his team discovered that the consumption of L-arginine by arginase or nitric oxide synthase changes the composition of the microbiota considerably and is damaging to the progression of intestinal inflammation. The lack of L-arginine led to increased inflammation of the intestinal mucosa, which was accompanied by an increase in the number of inflammatory cells and an increase in the number of blood vessels in the intestinal wall. On the other hand, starting a diet rich in L-arginine or eliminating enzymes that consume L-arginine (Arg1, NOS2) by using genetic engineering had a positive effect on the variety and abundance of the microbiota and accelerated the regression of intestinal inflammation. Using a variety of chemical, microbiological, genetic, and immunological methods of analysis, the researchers demonstrated that intestinal bacteria produce more polyamines at higher concentrations of L-arginine in the gut lumen. These polyamines activate genes that protect the intestinal epithelium and blood vessels, thus slowing down the progression of the disease. As an increased level of enzymes that consume L-arginine was found in the intestinal mucosa of patients with Crohn’s disease or ulcerative colitis, food supplements of L-arginine could be promising as a treatment of these debilitating diseases.

The study was funded among others by the German Research Foundation as part of FAU’s Collaborative Research Centre CRC 1181 ‘Checkpoints for resolution of inflammation’. More information is available on the website of the CRC.

Further information:

Prof. Dr. Jochen Mattner
Institute of Microbiology – Clinical Microbiology, Immunology and Hygiene
Phone +49 9131 85 23640
jochen.mattner@uk-erlangen.de

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