Amino acid balance in the gut plays critical role in intestinal
inflammation
8 August 2012
A molecular explanation for the increased susceptibility to
intestinal inflammation in malnutrition has been found by a research
group from the Institute of Molecular Biotechnology (IMBA) in Vienna,
Austria and the University of Kiel, Germany.
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 diarrhoea 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.
More than one billion people in poor countries are starving, and
malnutrition remains a major problem even in rich countries, making
it a leading cause of death in the world. For over a hundred 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 diarrhoea, 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.
"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”, says
Thomas Perlot, the first author of the study. “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.”
Josef Penninger, the lead author, says “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 needs to be carefully tested in clinical
trials.”