Zebrafish study shows key enzyme in gut is a peacemaker

Dec 12, 2007

University of Oregon scientists, using zebrafish to study the gastrointestinal tract, say that an enzyme long assumed to be involved in digestion instead is a detoxifying traffic cop, maintaining a friendly rapport between resident gut bacteria and cells.

A deficiency of the enzyme, intestinal alkaline phosphatase (Iap), said Karen Guillemin, a professor of molecular biology, appears to change the playing field inside the gut. Without Iap, an endotoxin called lipopolysaccharide (LPS), which resides in abundance on the gut, gains strength.

The UO pioneered the use of zebrafish as a model biological system for studying vertebrates, opening research windows on a growing list of human diseases. These new findings, reported in the December issue of the journal Cell Host & Microbe, are based on manipulations made in young, germ-free zebrafish and build upon key developmental discoveries involving the zebrafish gut that were published in 2006.

The implications, Guillemin said, could involve human inflammatory bowel diseases, including Crohn's disease, ulcerative colitis and necrotizing enterocolitis. The latter is a common gastrointestinal emergency in premature infants.

"We've shown that the bacteria that reside in our gut play an active role in modulating our immune response to them and help to prevent excessive inflammation," said Guillemin, who is a member of the UO's Institute of Molecular Biology. "There exists a give-and-take mutual co-existence of our resident bacteria and the cells of our gut."

In a 2006 study, Guillemin and colleagues showed that alkaline phosphatase is induced by LPS, a constituent of the outer membrane of all Gram-negative bacteria, in the early development of the gut's microbiota. The new study found that fish bred without Iap quickly become highly sensitive to LPS toxicity as do wild-type zebrafish when exposed to high levels of LPS. When Iap exists at sufficient levels the enzyme removes phosphates from LPS and turns it into a non-toxic molecule.

The new study is the first to show that LPS exposure in zebrafish causes symptoms that resemble septic shock in mice and humans. UO researchers also identified at least two cytokine genes involved in inflammation in the zebrafish. Cytokines are chemicals normally made by immune cells that boost the immune system to fight infectious pathogens and kill cancer cells.

While the ramifications to human gut diseases are speculative, Guillemin said, there is a lot of interest in connecting inflammatory bowel diseases with microbial changes. "At this point, there is no good understanding as to whether inflammation is caused by a shift in the bacteria present or the disease state changes the balance," she said. "We are not sure which may come first. And no one has looked at the normal variation of alkaline phosphatase in human intestines."

The possibility that the Iap-LPS balance may be contributing to necrotizing enterocolitis in premature babies is intriguing, she said. "So far, there is no real evidence for the involvement of a pathogen causing an infection," she explained. "The best predictor is how old premature infants are. This could represent the fact that this enzyme has not yet been expressed to protective levels."

Source: University of Oregon

Explore further: Injection technique creates opportunities for more effective crop protection

add to favorites email to friend print save as pdf

Related Stories

Physicists create new nanoparticle for cancer therapy

31 minutes ago

A University of Texas at Arlington physicist working to create a luminescent nanoparticle to use in security-related radiation detection may have instead happened upon an advance in photodynamic cancer therapy.

Breakthrough points to new drugs from nature

33 minutes ago

Researchers at Griffith University's Eskitis Institute have developed a new technique for discovering natural compounds which could form the basis of novel therapeutic drugs.

Recommended for you

Chimpanzees prefer firm, stable beds

4 hours ago

Chimpanzees may select a certain type of wood, Ugandan Ironwood, over other options for its firm, stable, and resilient properties to make their bed, according to a study published April 16, 2014 in the open-access ...

For cells, internal stress leads to unique shapes

5 hours ago

From far away, the top of a leaf looks like one seamless surface; however, up close, that smooth exterior is actually made up of a patchwork of cells in a variety of shapes and sizes. Interested in how these ...

Adventurous bacteria

6 hours ago

To reproduce or to conquer the world? Surprisingly, bacteria also face this problem. Theoretical biophysicists at Ludwig-Maximilians-Universitaet (LMU) in Munich have now shown how these organisms should ...

User comments : 0

More news stories

Chimpanzees prefer firm, stable beds

Chimpanzees may select a certain type of wood, Ugandan Ironwood, over other options for its firm, stable, and resilient properties to make their bed, according to a study published April 16, 2014 in the open-access ...

Revealing camouflaged bacteria

A research team at the Biozentrum of the University of Basel has discovered an protein family that plays a central role in the fight against the bacterial pathogen Salmonella within the cells. The so cal ...

Down's chromosome cause genome-wide disruption

The extra copy of Chromosome 21 that causes Down's syndrome throws a spanner into the workings of all the other chromosomes as well, said a study published Wednesday that surprised its authors.