For over more than a hundred years, experts have known that a lack of protein in the diet can lead to symptoms of ‘malnutrition’ including diarrhoea, inflamed intestines and other immune system disorders; all of which work to weaken the body and can be fatal.
However, the molecular mechanisms that explain how under-nourishment causes such severe symptoms has been largely unexplored, until now.
Led by Josef Penninger, director of the Institute of Molecular Biotechnology (IMBA) in Vienna, Austria, the research team report the discovery of a molecular explanation for the increased susceptibility to intestinal inflammation from poor nutrition.
Writing in Nature, the team reveal that the ACE2 enzyme controls how the intestines take in amino acids from food via amino acid transporters – in particular the uptake of the essential amino acid tryptophan.
"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”, said Thomas Perlot, 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,” he added.
The researchers initially set out to study the Angiotensin Converting Enzyme 2 (ACE2) – which helps to control blood pressure, kidney failure in diabetes, heart failure and lung injury. During study, the team identified the enzyme as the key receptor for SARS virus infections, but also discovered an entirely new function, they said.
“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,” said Penninger. “Biology continues to surprise me.”
The authors revealed ACE2 regulates changes in epithelial immunity and the gut microbiota balance, noting that such regulation is directly modified by the dietary amino acid tryptophan.
Too little tryptophan in the diet therefore lowers immune responses, and leads to changes in the gut bacteria, said the researchers. These changes lead to higher sensitivity and eventually diarrhoea and inflamed intestines.
However, simply increasing the intake of tryptophan in the diet provided relief for mice suffering from intestinal inflammation in the study, they said, adding that the mixture of bacteria returned to normal, inflammation died down, and the mice also became less susceptible to new attacks.
“Up to a billion people in the world are malnourished, especially the poor and disadvantaged,” said Penninger.
“I hope that our findings have opened a door to a better molecular understanding how malnutrition affects human health,” he said. “Whether simple tryptophan diets can indeed cure the effects of malnutrition in humans now needs to be carefully tested in clinical trials.”
Volume 487, Pages 477–481, doi: 10.1038/nature11228
“ACE2 links amino acid malnutrition to microbial ecology and intestinal inflammation”
Authors: Tatsuo Hashimoto, Thomas Perlot, Ateequr Rehman, Jean Trichereau, et al.