Five percent of all adults and seven to ten percent of all children suffer from Asthma bronchiale, and the numbers are growing. Scientists call this a multifactorial disease. Some of the factors that they have identified as relevant so far are genetic disposition, lifestyle and environmental influences, which particularly take effect during the critical early years of life. The illness is treatable but cannot be healed, which is why there is an urgent need for the development of new prevention and treatment options. The use of bacterial products is a new approach. “Today we know that the microbiome of the affected organs also changes with the disease, but little research has been conducted on the exact mechanisms,” explains Prof. Dr. Michael Schloter, Head of the Environmental Genomics Research Unit at the Helmholtz Zentrum München. Changes in the microbiome exacerbate the symptoms. “Therefore substances that help our microbiome to re-stabilize are very important, particularly in view of personalized medicine,” Schloter adds.
Focus on optical isomer of tryptophan
Scientists at the HMGU examined the immunomodulatory characteristics of a number of bacterial strains with probiotic properties. The discovery of D-tryptophan as an immunologically active substance in several Gram-positive bacteria of the Lactobacillusgenus was first made in the project network “Signal molecules in microbial biofilms” under the auspices of Prof. Dr. Susanne Krauss-Etschmann (previously with the Comprehensive Pneumology Center, now with the Leibniz Center in Borstel), Prof. Dr. Anton Hartmann (former head of the Microbe-Plant Interactions Research Unit, HMGU) and Prof. Dr. Philippe Schmitt-Kopplin (head of the Analytical BioGeoChemistry Research Unit, HMGU). The successful network was continued by Prof. Michael Schloter, Dr. Caspar Ohnmacht (ZAUM – Center of Allergy and Environment/TUM), and other colleagues, who examined the effect of D-tryptophan on microbiomes in animal models.
“The discovery of the rare D-enantiomer* of tryptophan as an active molecule initially surprised us, because only L-amino acids and D-sugars are known to form the basic building blocks of life,” explains Prof. Schmitt-Kopplin. “D-amino acids are much rarer than their L forms, but play an important biological role in Gram-positive bacteria and are particularly found in fermented food. It took interdisciplinary cooperation involving chemists, medical professionals, and biologists to identify the right-handed D form of this amino acid and one of its biological functions,” Schmitt-Kopplin adds. The interdisciplinary team was able to show that this new metabolite increased the number of regulatory T cells in the mouse model of asthma. At the same time, the Th2 response decreased and the inflammation and function of the animals’ lungs improved. This means that there was a reduction in the severity of the asthma. Krauss-Etschmann and her co-authors suspect that these changes are also tied to a shift in the microbiome of the intestine and lung that is triggered by D-tryptophan.
Selectively modifying the microbiome
Further experiments are needed to prove how sustainable the changes in microbiome structure and functions are as a result of optical isomers (enantiomers) of amino acids actually. The researcher team is also interested in the question which modes of action are in play and how D-tryptophan modifies the host cells. “Perhaps these substances will serve as a basis for deriving new prevention or treatment forms for allergic respiratory disorders,” the authors hope.