The intestines rely on different strategies to rebuild themselves in response to diet changes vs. infections, according to a new Cornell study – a finding that can shed light on how gut health adapts to harsh conditions, a flourishing ecosystem of microbes and a variable diet.
The findings, reported July 31 in Communications Biology, show that infectious damage causes cell loss and triggers stem cells to create new ones, while diet changes cause existing cells to grow or shrink.
“We want to understand the basic mechanisms of how stem cells respond to microbes and repair the gut because these findings will, we hope, ultimately help us address infections and diseases like Crohn’s and cancer,” said Nicolas Buchon, senior author of the paper and associate professor of entomology in the College of Agriculture and Life Sciences. “We may want to boost stem cell response to help with repair after a serious infection. Or we may want to limit stem cell proliferation if cells are responding aberrantly and building a tumor.”
Potential pharmaceuticals or therapeutics based on these findings are many years in the future, but basic discoveries like this one lay the foundation for future breakthroughs.
In 2009, Buchon and colleagues reported that when fruit flies were infected with the bacterium Erwinia carotovora (Ecc15), the microbes triggered an immune response and proliferation of stem cells. The finding helped establish how microbes can connect an immune response to stem-cell-driven repair in the intestine.
The current study also relies on fruit flies and Ecc15, but this paper explores the interplay of infection and nutritional status at the same time. Scientists studying the gut generally examine one factor or the other, and that division has led to very different assumptions about how the intestines adapt and rebuild, Buchon said.
“If you study the gut from the perspective of nutrition, you can conclude that the gut is constantly shifting and adapting: Feed less, the gut will shrink; eat more nutritious food, it will expand,” he said. “If you look at microbes and infection, the key word is always homeostasis. That means if you damage the gut, it will rebuild back to its former state. So our question was, well, which one is it? Can we manipulate food, manipulate microbes and play with the complete matrix to see how the gut responds to all of those stimuli at once?”
In their experiments on fruit flies – a model organism frequently used by scientists to make discoveries in basic biology that apply to all multicellular organisms, including humans – they found:
- The consequences of an infection on the intestines depends on the initial health and size of those intestines. In a well-nourished organism, infection causes the intestine to shrink quickly and dramatically. In a malnourished organism, the already small intestine shrinks much less, and infectious microbes became a food source more than a threat.
- The intestine rebuilt according to the nutritional environment in which recovery occurred. “This challenges a simple view of intestinal homeostasis in which damage is followed by restoration to a fixed, pre-injury size,” Buchon said.
- The intestines use different methods to grow, shrink and adapt in response to diet changes vs. infections. Improved nutrition makes existing cells bigger, while infectious damage causes cell death and replacement by intestinal stem cells.
Future research will seek to understand the molecular mechanisms and pathways that the intestines use to sense microbes and nutrients and guide the appropriate response.
First author of the paper is Alessandro Bonfini, formerly a postdoctoral associate in Buchon’s lab and now assistant professor at Zhejiang University-University of Edinburgh Institute. Funding support came from the National Institutes of Health and the National Science Foundation.
Krisy Gashler is a writer for the College of Agriculture and Life Sciences.
