Biologists control gut inflammation by altering the abundance of resident bacteria

February 16, 2017, University of Oregon

Numerous human diseases, including inflammatory bowel disease, diabetes and autism spectrum disorders have been linked to abnormal gut microbial communities, or microbiomes, but an open question is whether these altered microbiomes are drivers of disease.

A new study at the University of Oregon, led by postdoctoral fellow Annah Rolig, took aim at that question with experiments in zebrafish to dissect whether changes in the abundance of certain can cause intestinal inflammation.

The study, published Feb. 16 in PLOS Biology, made use of a mutant zebrafish strain that models human Hirschsprung disease, which is caused by loss of the gut neurons that coordinate gut contractions.

Just like Hirschsprung disease patients, who sometimes develop an inflammatory condition called Hirschsprung-associated enterocolitis, a subset of the developed intestinal inflammation.

The researchers successfully tracked how gut bacterial abundances influenced inflammation. Fish with intestinal inflammation had a larger abundance of a subset of that appeared to be pro-inflammatory, which they confirmed by dosing the fish with one of these bacteria and finding that it increased the severity of disease symptoms.

They also found a subset of bacteria that was depleted in the inflamed intestines, but present in the mutant fish that remained disease-free. Dosing the fish with a strain of these depleted bacteria ameliorated the disease. Finally, they showed that they could cure the inflammation by transplanting gut neurons from healthy fish into the diseased fish.

These studies demonstrate that inflammatory intestinal pathologies, such as Hirschsprung-associated enterocolitis or , can be explained as an overgrowth of certain pro-inflammatory groups of bacteria or a loss of anti-inflammatory bacteria, said Judith Eisen, a professor of biology and an expert on gut neurons in zebrafish.

The study stems from a long-term collaboration between Eisen and Karen Guillemin, who studies gut bacteria and inflammation.

"When we started this work, very few people were thinking about how the nervous system and gut bacteria interact," said Eisen, who is a member of the UO's Institute of Neuroscience. "Our studies demonstrate how important it is to consider all the interacting cells of an organ, including the microbial cells."

"Human microbiomes can be overwhelmingly variable due to differences between people's environments, diets and genetics," said Guillemin, a biologist and member of the UO's Institute of Molecular Biology. "The zebrafish model allowed us to control those variables and see how bacterial strains tracked with inflammation. From these patterns, we could show that the drivers of disease can be a very few members of a complex microbial community."

Identifying the bacteria that drive and protect against disease is the first step toward developing microbial interventions and therapies, said Rolig, a postdoctoral researcher in the UO's Institute of Molecular Biology.

"The fact that we could alleviate inflammation by adding back a single key bacterial strain, suggests that it could be useful as a probiotic for inflammatory diseases," said Rolig, who, along with Eisen, is a scientist in the National Institutes of Health-funded Microbial Ecology and Theory of Animals Center for Systems Biology, known as the META Center, which Guillemin heads.

The next steps for the research group are to use what they have learned from this zebrafish model of to design better probiotics to treat .

Explore further: Scientists identify mechanisms driving gut bacterial imbalance and inflammation

More information: PLOS Biology, DOI: 10.1371/journal.pbio.2000689

Related Stories

Scientists identify mechanisms driving gut bacterial imbalance and inflammation

February 8, 2017
A study led by UT Southwestern Medical Center researchers has uncovered key molecular pathways behind the disruption of the gut's delicate balance of bacteria during episodes of inflammatory disease.

Study suggests some gut microbes may be keystones of health

November 11, 2015
University of Oregon scientists have found that strength in numbers doesn't hold true for microbes in the intestines. A minority population of the right type might hold the key to regulating good health.

Newly discovered bacteria-binding protein in the intestine

December 8, 2016
Deficiency in a certain protein in the gastrointestinal tract has been shown to lead to both inflammation and abdominal fat accumulation in mice. The discovery provides yet another piece of the puzzle of how humans are affected—or ...

Researchers find bacterial protein that boosts insulin-producing cells in zebrafish

December 13, 2016
A newly discovered bacterial protein produced in the zebrafish gut triggers insulin-producing beta cells of the pancreas to multiply during early larval development, say University of Oregon researchers.

Recommended for you

Research team diagnoses asthma with nasal brush test

June 11, 2018
Mount Sinai researchers have identified a genetic biomarker of asthma that can be tested for using a simple nasal brush and basic follow-up data analysis. This inexpensive diagnostic test can accurately identify mild to moderate ...

Eosinophilic esophagitis may be due to missing protein

June 7, 2018
Scientists have discovered that the absence of a specific protein in cells lining the esophagus may cause inflammation and tissue damage in people with eosinophilic esophagitis (EoE). EoE affects as many as 150,000 people ...

Mouse study links triclosan, a common antimicrobial, to colonic inflammation

May 30, 2018
A large research team led by senior author Guodong Zhang at the University of Massachusetts Amherst reports that the antimicrobial ingredient triclosan, found in hand soaps and toothpastes among other products, could have ...

Body knows best: A natural healing mechanism for inflammatory bowel disease

May 30, 2018
Treating inflammatory diseases of the bowel is extremely challenging: Genes, gut microbes and disrupted immune function all contribute. Weizmann Institute of Science researchers are proposing a way around this complexity. ...

Chance discovery links inflammatory bowel disease with common bacterial gut toxin

May 17, 2018
New research has uncovered a surprise link between a common bacterial toxin found in the gut and inflammatory bowel disease (IBD).

New cytokine network can repair tissue damage in the intestine, study finds

May 16, 2018
A new group of proteins called cytokines, critical for antimicrobial activity and repairing the damaged intestinal tissue found in inflammatory bowel disease (IBD), has been discovered by researchers in a study led by Georgia ...

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.