Pakistani stem cell researchers to grow mini-intestines in a unique study into malnutrition

KARACHI: Karachi Researchers at the Aga Khan University are harnessing the power of stem cells to create mini-intestines that can generate new insights into how malnutrition occurs.

Malnutrition is a major public health problem in the developing world, with four out of ten children under the age of five in Pakistan suffering from stunting while one in three children is underweight, according to the National Nutrition Survey 2018.

An unhygienic environment, contaminated water, inadequate diet and poor maternal health during pregnancy are some of the major factors leading to environmental enteropathy or EE. EE is an important but poorly understood intermediary condition, which is characterised by inflammation of the gut, that leads to chronic malnutrition.

Existing research into malnutrition has extensively documented its causes and shed light on the structural and genetic differences between a healthy and a malnourished intestine. However, until now, researchers have been unable to explore how EE originates at the cell level because of a range of ethical limitations and practical obstacles, especially in young children. Therefore, studies into the genesis of EE requires to require models of healthy and malnourished guts to be developed to explore disease processes.

The Aga Khan University’s Juma research laboratory is one of the few facilities in South Asia and is among a select few in the world that have succeeded in growing enteroids or mini-intestines from gut biopsy tissue.

“Stem cell technology has enabled us to successfully grow intestinal organoids, or mini-intestines, from the tissue of malnourished children,” said AKU’s Dr Junaid Iqbal. “This provides us with an excellent model to safely conduct experiments to explore disease processes, study gut infections and vaccine failure in malnourished children, and identify different therapeutic strategies to reverse the effects of environmental enteropathy. This may increase the chances of healthy growth in our children.”

Dr Iqbal and his team member AKU Assistant Professor Dr Zehra Jamil have received training on going these enteroids from one of the world’s leading laboratories at the University of Virginia.

In an extension of their work on malnutrition, the AKU faculty, in collaboration with researchers at the University of Virginia, will study the effects of COVID-19 infection on a malnourished gut, one of the first such studies in the world.

Recent studies into the coronavirus have noted that the ACE-2 receptor, a protein that provides a pathway for the virus into the body’s cells, is present in both the respiratory system as well as the gut. This means that the coronavirus also infects and grows inside our gut, which could explain COVID-19 symptoms such as an upset stomach and fatigue.

The study will see researchers expose a range of gut enteroids to the virus to explore how COVID-19 multiplies in the intestine. They will also conduct studies to understand infection dynamics in young versus old people and to judge how well-malnourished guts can defend against the virus.

“Malnutrition is a major issue that limits children’s growth, cognitive potential, and overall immune response,” said Dr Iqbal. “Since it’s so prevalent in the developing world, it is possible that it plays a role in the pathogenesis and spread of COVID-19 across Pakistan and other countries in the South Asian region.

COVID-19 in the presence of malnutrition may further deteriorate children’s development in our part of the world. That’s why this study is so important.”

The study has received funding from the Bill and Melinda Gates Foundation. Its goals are in line with targets under goal 2 of the global Sustainable Development Goals: end hunger, achieve food security and improved nutrition and promote sustainable agriculture, which calls for special efforts to end all forms of malnutrition and stunting in children under the age of five by 2030.