Mice fed tryptophan develop immune cells that foster a tolerant gut

August 3, 2017
Credit: Martha Sexton/public domain

Immune cells patrol the gut to ensure that harmful microbes hidden in the food we eat don't sneak into the body. Cells that are capable of triggering inflammation are balanced by cells that promote tolerance, protecting the body without damaging sensitive tissues. When the balance tilts too far toward inflammation, inflammatory bowel disease can result.

Now, researchers at Washington University School of Medicine in St. Louis have found that a kind of tolerance-promoting immune cell appears in mice that carry a specific bacterium in their guts. Further, the bacterium needs —one of the building blocks of proteins—to trigger the cells' appearance.

"We established a link between one bacterial species—Lactobacillus reuteri—that is a normal part of the , and the development of a population of cells that promote tolerance," said Marco Colonna, MD, the Robert Rock Belliveau MD Professor of Pathology and the study's senior author. "The more tryptophan the mice had in their diet, the more of these immune cells they had."

If such findings hold true for people, it would suggest that the combination of L. reuteri and a tryptophan-rich diet may foster a more tolerant, less inflammatory gut environment, which could mean relief for the million or more Americans living with the abdominal pain and diarrhea of .

The study is published Aug. 3 in the journal Science.

Postdoctoral researcher Luisa Cervantes-Barragan, PhD, was studying a kind of immune cell that promotes tolerance when she discovered that one group of study mice had such cells, while a second group of study mice that were the same strain of mice but were housed far apart from the first group did not have such cells.

The mice were genetically identical but had been born and raised separately, indicating that an environmental factor influenced whether the immune cells developed.

She suspected the difference had to do with the mice's gut microbiomes—the community of bacteria, viruses and fungi that normally live within the gastrointestinal tract.

Cervantes-Barragan collaborated with Chyi-Song Hsieh, MD, PhD, the Alan A. and Edith L. Wolff Distinguished Professor of Medicine, to sequence DNA from the intestines of the two groups of mice. They found six bacterial species present in the mice with the immune cells but absent from the mice without them.

With the help of Jeffrey I. Gordon, MD, the Dr. Robert J. Glaser Distinguished University Professor, the researchers turned to mice that had lived under sterile conditions since birth to identify which of the six species was involved in inducing the immune cells. Such mice lack a gut microbiome and do not develop this kind of immune cell. When L. reuteri was introduced to the germ-free mice, the immune cells arose.

To understand how the bacteria affected the immune system, the researchers grew L. reuteri in liquid and then transferred small amounts of the liquid—without bacteria—to immature immune cells isolated from mice. The developed into the tolerance-promoting cells. When the active component was purified from the liquid, it turned out to be a byproduct of tryptophan metabolism known as indole-3-lactic acid.

Tryptophan—commonly associated with turkey—is a normal part of the mouse and the human diet. Protein-rich foods contain appreciable amounts: nuts, eggs, seeds, beans, poultry, yogurt, cheese, even chocolate.

When the researchers doubled the amount of tryptophan in the mice's feed, the number of such cells rose by about 50 percent. When tryptophan levels were halved, the number of cells dropped by half.

People have the same tolerance-promoting cells as mice, and most of us shelter L. reuteri in our gastrointestinal tracts. It is not known whether tryptophan byproducts from L. reuteri induce the cells to develop in people as they do in , but defects in genes related to tryptophan have been found in people with inflammatory bowel disease.

"The development of these cells is probably something we want to encourage since these control inflammation on the inner surface of the intestines," Cervantes-Barragan said. "Potentially, high levels of tryptophan in the presence of L. reuteri may induce expansion of this population."

Explore further: Gut bacteria may hold key to treating autoimmune disease

More information: "Lactobacillus reuteri induces gut intraepithelial CD4+CD8αα+ T cells" Science (2017). science.sciencemag.org/lookup/ … 1126/science.aah5825

Related Stories

Gut bacteria may hold key to treating autoimmune disease

December 19, 2016
Defects in the body's regulatory T cells (T reg cells) cause inflammation and autoimmune disease by altering the type of bacteria living in the gut, researchers from The University of Texas Health Science Center at Houston ...

Gut check: A molecule that balances the immune system in the gut

June 13, 2017
A healthy gut requires a molecule called gp96 to train the immune system to tolerate food and normal microbes, report researchers at the Medical University of South Carolina (MUSC) in the May 19, 2017 issue of Scientific ...

High-fat diet leads to same intestinal inflammation as a virus

June 22, 2017
A new study by scientists at UCLA found that when mice eat a high-fat diet, the cells in their small intestines respond the same way they do to a viral infection, turning up production of certain immune molecules and causing ...

Cytokine controls immune cells that trigger inflammatory bowel disease, study finds

April 18, 2017
A certain cytokine, or small protein that helps cells communicate during immune responses, can control whether immune cells promote or suppress inflammatory bowel disease, a finding that could lead to new treatments, according ...

New report links early life antibiotic use to inflammatory gut diseases in adulthood

April 3, 2017
A new research report in the Journal of Leukocyte Biology involving mice shows that antibiotic use very early in life that alters the normal development/growth of gut bacteria, may contribute to the development of inflammatory ...

Accelerated immune aging may contribute to obesity-linked metabolic disease

November 7, 2016
Obese individuals are at an elevated risk of developing comorbid cardiovascular and metabolic diseases, such as type 2 diabetes. Some research suggests that these comorbid diseases develop in response to chronic inflammation ...

Recommended for you

Antibody protects against Zika and dengue, mouse study shows

September 25, 2017
Brazil and other areas hardest hit by the Zika virus - which can cause babies to be born with abnormally small heads - are also home to dengue virus, which is spread by the same mosquito species.

Gene immunotherapy protects against multiple sclerosis in mice

September 21, 2017
A potent and long-lasting gene immunotherapy approach prevents and reverses symptoms of multiple sclerosis in mice, according to a study published September 21st in the journal Molecular Therapy. Multiple sclerosis is an ...

New academic study reveals true extent of the link between hard water and eczema

September 21, 2017
Hard water damages our protective skin barrier and could contribute to the development of eczema, a new study has shown.

Exposure to pet and pest allergens during infancy linked to reduced asthma risk

September 19, 2017
Children exposed to high indoor levels of pet or pest allergens during infancy have a lower risk of developing asthma by 7 years of age, new research supported by the National Institutes of Health reveals. The findings, published ...

Cholesterol-like molecules switch off the engine in cancer-targeting 'Natural Killer' cells

September 18, 2017
Scientists have just discovered how the engine that powers cancer-killing cells functions. Crucially, their research also highlights how that engine is fuelled and that cholesterol-like molecules, called oxysterols, act as ...

MicroRNA helps cancer evade immune system

September 18, 2017
The immune system automatically destroys dysfunctional cells such as cancer cells, but cancerous tumors often survive nonetheless. A new study by Salk scientists shows one method by which fast-growing tumors evade anti-tumor ...

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

betterexists
not rated yet Aug 03, 2017
Our Science is Not even at infancy; We Cook our Food. Birds that stick their beaks into soil every minute and even into muddy pond sediments at the shores live by happily. The Simple Question is How Come ?

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.