VIENNA—For more than 100 years, doctors have known that a lack of protein in the diet or low levels of amino acids, the building blocks of proteins, can lead to symptoms like diarrhea, inflamed intestines and other immune system disorders, which weaken the body and can be fatal. However, the molecular mechanism which explains how malnutrition causes such severe symptoms has been largely unexplored.
Now a research group led by Josef Penninger, the director of the Institute of Molecular Biotechnology (IMBA) in Vienna, Austria, in cooperation with Philip Rosenstiel, University of Kiel, Germany, has found a molecular explanation for the increased susceptibility to intestinal inflammation in malnutrition.
The researchers were studying an enzyme which helps to control blood pressure, kidney failure in diabetes, heart failure and lung injury, called the Angiotensin Converting Enzyme 2, or ACE2. This enzyme was identified as the key receptor for SARS virus infections, but the researchers also discovered an entirely new function. ACE2 controls the way our intestines take in amino acids from our food, via amino acid transporters, and in particular the uptake of the essential amino acid tryptophan.
Too little tryptophan alters our natural immune system, which changes the types of bacteria which can live in our bowels and guts, leading to higher sensitivity and eventually diarrhea and inflamed intestines. Increasing the intake of tryptophan in their diet provided relief for mice suffering from intestinal inflammation. The mixture of bacteria returned to normal, the inflammation died down, and the mice also became less susceptible to new attacks.