Starvation and malnutrition are still major problems and leading causes of mortality worldwide. Over a billion people are starving in poor countries and malnutrition affects rich countries, as well.

Doctors have known for over a century that a diet lacking in protein or low levels of amino acids, which are the building blocks of proteins, can cause symptoms like diarrhea, inflamed intestines and other immune system disorders that weaken the body and can potentially prove fatal. So far, there has been insufficient research into the molecular mechanism of malnutrition to explain the causes for these severe symptoms.

The paper “ACE2 links amino acid malnutrition to microbial ecology and intestinal inflammation”, published in the July 26 issue of Nature reports that Josef Penninger, Director of the Institute of Molecular Biotechnology (IMBA) in Vienna, Austria and Philip Rosenstiel from Kiel University in Germany, have now discovered a molecular explanation for the increased susceptibility to intestinal inflammation in malnutrition.

During research of an enzyme called Angiotensin Converting Enzyme 2 (ACE2), which is involved in controlling blood pressure, kidney failure in diabetes, heart failure and lung injury, the team identified the enzyme as the key receptor for SARS virus infections. However, they also discovered an entirely new function; ACE2 controls the intake of amino acids from food into the intestines via amino acid transporters, particularly the intake of tryptophan, an essential amino acid.

If the body has insufficient amounts of tryptophan, its natural immune system is changed, altering the types of bacteria that live in the bowel and guts, which elevates the body’s sensitivity and eventually leads to diarrhea and inflamed intestines. A higher intake of tryptophan in the diet was observed to provide relief in mice with intestinal inflammation. The natural balance of the bacteria mix was restored, causing inflammation to subside and leaving the mice less susceptible to new attacks.

First author of the study, Thomas Perlot, states:

“The research shows how the food we eat can directly change the good bacteria in our intestines to bad bacteria and so influence our health. Our results might also explain nutritional effects that have been known for centuries and provide a molecular link between malnutrition and the bacteria living in our intestines. This discovery could be used in the future to treat patients with a simple regulated diet or by taking tryptophan as a food supplement. And there is hardly any risk of side effects from artificially increasing an amino acid found in the normal diet.”

Leading author, Josef Penninger, concluded:

“I have studied ACE2 for more than 10 years and was completely stunned by this novel link between ACE2 and amino acid balance in the gut. Biology continues to surprise me. Up to a billion people in the world are malnourished, especially the poor and disadvantaged. In Austria alone, around 80,000 people suffer from a chronic inflammatory bowel disease like ulcerative colitis or Crohn’s disease. I hope that our findings have opened a door to a better molecular understanding how malnutrition affects human health. Whether simple tryptophan diets can indeed cure the effects of malnutrition in humans now need to be carefully tested in clinical trials.”

Written By Petra Rattue