Zebrafish provide a novel model to study short bowel syndrome

June 19, 2015, Children's Hospital Los Angeles

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 Journal of Physiology-Gastrointestinal and Liver Physiology.

SBS is a highly morbid disease where the is either shortened or non-functional, leaving the patient with the inability to absorb enough nutrients from food. This results in profound malnutrition, dehydration, and can be fatal.

Some patients increase their ability to absorb nutrition through their shorter intestine through a process called adaptation, which is not well understood. The CHLA group is the first to model adaptation in an innovative way that markedly shortens the time to study the condition and the costs of these experiments.

'The new solution from our lab is to study the intestines in small fish that could fit onto a dime,' explained principal investigator Tracy C. Grikscheit, M.D., of The Saban Research Institute of Children's Hospital Los Angeles. 'Even though the fish are tiny, under a microscope, we are able to perform the same surgery that is performed on children with short bowel syndrome. And even better, we have pioneered a way to show the resulting changes in the anatomy through three dimensional imaging of the fish, with higher resolution than some scans available to human patients.'

The researchers can 'fly' through these tiny fish in three dimensions, and watch the changes in their intestines in order to better understand what is happening for human patients, enabling them to better understand the problem and identify potential solutions. A sample of the three-dimensional imaging video is available here: https://youtu.be/NF-bRwPNjuY.

'The three-dimensional reconstructions of these fish shown in our publication make it clear that the changes in the fish intestine after this surgery are just like those seen in the babies we care for,' said Grikscheit, who is also an associate professor of surgery at the Keck School of Medicine of the University of Southern California. 'As a pediatric surgeon, my lab has only one goal: to find better options for children with short bowel syndrome.'

Operating on may seem like an unlikely decision, but they are increasingly being studied by investigators who are interested in stem and progenitor cells because these cells have a high capacity for regeneration and have many similarities to humans. The investigators proved that the model of short bowel syndrome in zebrafish resulted in adaptation of the intestine, and a marked increase in two weeks after surgery. In addition, the investigators could dose the fish with drugs to investigate the mechanism of adaptation just by dropping the compounds in the tank water—a significantly easier and less expensive approach than in other models.

Marked adaptation was documented in the , and this advance has now opened up a wide range of possible studies in which the cells that proliferate rapidly, as well as the signaling pathways that promote adaptation, can be identified. The hope is that these data can lead to better care for babies who suffer from intestinal failure.

'We and others have struggled to understand adaptation in order to improve our patients' lives. Because we can only look at tissue from humans at various times when they need surgery, and other models are very expensive and difficult, this is a solid advance that we expect to propel us to a new understanding of a process that is so important to our babies with inadequate intestine,' said first author Kathy Schall, M.D., of Children's Hospital Los Angeles.

Explore further: New hope for short bowel syndrome

More information: American Journal of Physiology-Gastrointestinal and Liver Physiology, Published 18 June 2015, DOI: 10.1152/ajpgi.00311.2014

Related Stories

New hope for short bowel syndrome

May 4, 2015
Researchers at Children's Hospital Los Angeles have successfully made a small intestine that has the structural and molecular components of a healthy intestine.

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 ...

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 ...

Artificial intestine to treat youths' bowel disorder

December 9, 2011
(Medical Xpress) -- A tiny 3-D collagen "scaffold" developed in a Cornell lab could prove a lifesaver for those who have lost parts of their intestine.

Six months of fish oil reverses liver disease in children with intestinal failure, study shows

August 14, 2013
Children who suffer from intestinal failure, most often caused by a shortened or dysfunctional bowel, are unable to consume food orally. Instead, a nutritional cocktail of sugar, protein and fat made from soybean oil is injected ...

Recommended for you

Researchers identify blood biomarkers that may help diagnose, confirm concussions

April 20, 2018
Researchers from the University of California, Irvine, Georgetown University and the University of Rochester have found that specific small molecules in blood plasma may be useful in determining whether someone has sustained ...

Stem-cell technology aids 3-D printed cartilage repair

April 20, 2018
Novel stem-cell technology developed at Swinburne will be used to grow the massive number of stem cells required for a new hand-held 3-D printer that will enable surgeons to create patient-specific bone and cartilage.

DOR protein deficiency favors the development of obesity

April 20, 2018
Obesity is a world health problem. Excessive accumulation of fat tissue (adipose tissue) increases the risk of cardiovascular disease, hypertension, diabetes and some types of cancer. However, some obese individuals are less ...

Defect in debilitating neurodegenerative disease reversed in mouse nerves

April 19, 2018
Scientists have developed a new drug compound that shows promise as a future treatment for Charcot-Marie-Tooth disease, an inherited, often painful neurodegenerative condition that affects nerves in the hands, arms, feet ...

Enduring cold temperatures alters fat cell epigenetics

April 19, 2018
A new study in fat cells has revealed a molecular mechanism that controls how lifestyle choices and the external environment affect gene expression. This mechanism includes potential targets for next-generation drug discovery ...

Molecule that dilates blood vessels hints at new way to treat heart disease

April 19, 2018
Americans die of heart or cardiovascular disease at an alarming rate. In fact, heart attacks, strokes and related diseases will kill an estimated 610,000 Americans this year alone. Some medications help, but to better tackle ...


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.