Short bowel syndrome results in changes to gene expression

January 25, 2017
Credit: CC0 Public Domain

Investigators at Children's Hospital Los Angeles, led by Tracy C. Grikscheit, MD, have mapped the genetic changes resulting from short bowel syndrome (SBS) using a novel zebrafish model and by performing intensive gene sequencing. This approach to determining which genes are markedly over or under expressed in SBS may assist scientists in developing future therapies for children and adults with this condition. Results of the study will be published in BioMed Central Genomics on January 25.

Necrotizing enterocolitis in premature infants, Crohn's disease in children and adults and trauma can necessitate the removal of significant quantities of resulting in SBS and subsequently, in the body being unable to absorb nutrition from food because of an inadequate length of small intestine. In children, the incidence of SBS is almost double that of childhood cancer and the mortality rate at 5 years following surgery is approximately 30 percent. Until now, the morbidity and mortality associated with SBS has been related to malnutrition and liver fibrosis from intravenous nutritional products. In this study the researchers sought to determine systemic effects attributable to the disease process alone.

The research team conducted the study in zebrafish, using a validated SBS model created in the Grikscheit laboratory. This model allowed the investigators to study matched samples of small intestine from zebrafish who had bowel surgery and those who underwent "sham" or control surgery. According to first author, Kathy A. Schall, MD, "Most studies of SBS focus on the epithelial cells that line the intestine but this model allowed us to focus on systemic effects and the associated genetic alterations responsible for those effects."

The paper reports that 29 fish had intestinal surgery compared to 28 fish that received sham surgery. After two weeks, a time previously determined to be associated with maximal stem and progenitor cell activity, RNA-sequencing analysis was performed. Zebrafish with SBS had 1346 significantly upregulated genes and 678 significantly downregulated genes compared to sham-operated controls. The upregulated genes were related to processes that include cell proliferation, acute phase response signaling, innate and adaptive immunity, bile acid regulation, production of nitric oxide and reactive oxygen species, cellular barrier maintenance and coagulation. Downregulated genes were associated with folate synthesis, gluconeogenesis, glycogenolysis, fatty-acid oxidation and activation and drug and steroid metabolism.

"We've identified marked changes in several metabolic pathways - including some that had previously been considered an effect of intravenous nutrition," said Grikscheit, who is also a tenured associate professor of surgery at the Keck School of Medicine of the University of Southern California. "Knowing that these alterations are caused by SBS in the absence of intravenous nutrition provides us multiple targets for developing new therapies to modify these effects. Instead of digging in random places we now have a map to follow in our search for therapeutic approaches for SBS." Grikscheit adds that a reduction of just 10 percent of U.S. patients requiring home intravenous nutrition for SBS would result in an estimated saving of nearly $800 million in health care costs.

Explore further: Zebrafish provide a novel model to study short bowel syndrome

Related Stories

Zebrafish provide a novel model to study short bowel syndrome

June 19, 2015
Investigators at Children's Hospital Los Angeles are providing new hope for babies with short bowel syndrome (SBS) by developing a novel model of SBS in zebrafish, described in a paper published online on June 18 by the American ...

Scientists develop tissue-engineered model of human lung and trachea

November 11, 2016
Scientists at Children's Hospital Los Angeles have developed a tissue-engineered model of lung and trachea which contains the diverse cell types present in the human respiratory tract. The study, led by principal investigator ...

Culture crash: How common pediatric diseases affect the healthy intestinal microbiome

June 13, 2016
Tracy C. Grikscheit, MD, pediatric surgeon and principal investigator at The Saban Research Institute of Children's Hospital Los Angeles, treats a large number of young patients who require surgery for various intestinal ...

Researchers grow functional tissue-engineered intestine from human cells

January 8, 2015
A new study by researchers at Children's Hospital Los Angeles has shown that tissue-engineered small intestine grown from human cells replicates key aspects of a functioning human intestine. The tissue-engineered small intestine ...

Functional human tissue-engineered liver generated from stem and progenitor cells

August 30, 2016
A research team led by investigators at The Saban Research Institute of Children's Hospital Los Angeles has generated functional human and mouse tissue-engineered liver from adult stem and progenitor cells. Tissue-engineered ...

Researchers engineer functioning small intestine in laboratory experiments

July 5, 2011
Researchers at The Saban Research Institute of Children's Hospital Los Angeles have successfully created a tissue-engineered small intestine in mice that replicates the intestinal structures of natural intestine -- a necessary ...

Recommended for you

Large genetic study links tendency to undervalue future rewards with ADHD, obesity

December 11, 2017
Researchers at University of California San Diego School of Medicine have found a genetic signature for delay discounting—the tendency to undervalue future rewards—that overlaps with attention-deficit/hyperactivity disorder ...

Gene variants identified that may influence sexual orientation in men and boys

December 8, 2017
(Medical Xpress)—A large team of researchers from several institutions in the U.S. and one each from Australia and the U.K. has found two gene variants that appear to be more prevalent in gay men than straight men, adding ...

Disease caused by reduction of most abundant cellular protein identified

December 8, 2017
An international team of scientists and doctors has identified a new disease that results in low levels of a common protein found inside our cells.

Study finds genetic mutation causes 'vicious cycle' in most common form of amyotrophic lateral sclerosis

December 8, 2017
University of Michigan-led research brings scientists one step closer to understanding the development of neurodegenerative disorders such as ALS.

Mutations in neurons accumulate as we age: The process may explain normal cognitive decline and neurodegeneration

December 7, 2017
Scientists have wondered whether somatic (non-inherited) mutations play a role in aging and brain degeneration, but until recently there was no good technology to test this idea. A study published online today in Science, ...

Researchers find genes may 'snowball' obesity

December 7, 2017
There are nine genes that make you gain more weight if you already have a high body mass index, McMaster University researchers have found.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.