Commonly associated with turkey, the amino acid tryptophan is found in lots of protein-rich foods, like dairy, nuts, and beans. Now scientists think it may play a key role in healthy guts.
Immune cells patrol the gut to make sure 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.
“The more tryptophan the mice had in their diet, the more of these immune cells they had.”
But when the balance tilts too far in the wrong direction, inflammatory bowel disease can be the result.
Researchers have discovered that a kind of tolerance-promoting immune cell appears in mice that carry a specific bacterium in their guts. The bacterium needs tryptophan—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 gut microbiome, and the development of a population of cells that promote tolerance,” says Marco Colonna, professor of pathology at Washington University in St. Louis and senior author of the study in the journal Science. “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 inflammatory bowel disease.
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Postdoctoral researcher Luisa Cervantes-Barragan 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 didn’t.
The mice were genetically identical but had been born and raised separately, indicating that an environmental factor influenced whether the immune cells developed.
Double the tryptophan
Cervantes-Barragan 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.
The researchers sequenced DNA from the intestines of the two groups of mice and found six bacterial species present in the mice with the immune cells but absent from the mice without them.
They then 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 don’t develop this kind of immune cell. When L. reuteri was introduced to the germ-free mice, the immune cells arose.
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To understand how the bacteria affected the immune system, researchers grew L. reuteri in liquid and then transferred small amounts of the liquid—without bacteria—to immature immune cells isolated from mice. The immune cells 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 is a normal part of the mouse and the human diet. Protein-rich foods—nuts, eggs, seeds, beans, poultry, yogurt, cheese, and even chocolate—contain appreciable amounts.
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 mice, 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 cells control inflammation on the inner surface of the intestines,” Cervantes-Barragan says. “Potentially, high levels of tryptophan in the presence of L. reuteri may induce expansion of this population.”
The National Institutes of Health; the Kenneth Rainin Foundation; Burroughs Wellcome Fund; and the Swiss National Science Foundation funded the work.
