A properly functioning body absorbs most nutrients in the bloodstream through the wall of the small intestine, with the rest of the nutrients absorbed through the large intestine. However, in many cases this process doesn't function as it should, impairing absorption of macronutrients and micronutrients.
“Poor absorption of macronutrients is a global health concern, with underlying etiology including short-gut syndrome, enteric pathogen infection, and malnutrition,” note researchers in a new study. “Therefore, identification of factors regulating nutrient absorption has significant therapeutic potential.”
To gain a better understanding of the mechanisms behind the malabsorption, scientists at Cincinnati Children's Hospital Medical Center used human intestinal organoids grown from stem cells to discover how human bodies control the absorption of nutrients. Their research led them to one hormone that might be key in solving this puzzle.
Heather A. McCauley, PhD, a research associate at the institution, found that the hormone peptide YY, also called PYY, can reverse congenital malabsorption in mice. With a single PYY injection per day, 80% of the mice survived, compared to the 20% to 30% typical survival rate.
This indicates PYY may be a possible therapeutic for people with severe malabsorption -- including the possibility of reversing a congenital disorder in babies who cannot adequately absorb nutrients and need intravenous feeding to survive.
Babies born with enteroendocrine cells that don't function properly, or in some cases born with no enteroendocrine cells at all, have severe malabsorption and require IV nutrition.
"This study allowed us to understand how important this one rare cell type is in controlling how the intestine absorbs nutrients and functions on a daily basis," McCauley said.
The research, published in Nature Communications, reported that the absorption of nutrients, especially carbohydrates and proteins, is controlled by enteroendocrine cells in the gastrointestinal tract.
The Cincinnati Children's study was the first to describe a mechanism linking enteroendocrine cells to the absorption of macronutrients like carbohydrates and amino acids.
One key finding of the study is how these cells, upon sensing ingested nutrients, prepare the intestine to absorb nutrients by controlling the influx and outflux of electrolytes and water, the researchers stated. Absorption of carbohydrates and protein is then linked to the movement of ions in the intestine.
"What this study highlights is how decades of basic research into how organs are made and how they function is now leading to breakthroughs in identifying new therapeutics," said James Wells, PhD, senior author of the study and chief scientific officer of the Center for Stem Cell and Organoid Medicine (CuSTOM) at Cincinnati Children's.
Source: Nature Communications
11, 4791 (2020). https://doi.org/10.1038/s41467-020-18536-z
“Enteroendocrine cells couple nutrient sensing to nutrient absorption by regulating ion transport”
Authors: H. McCauley, et al.