Insufficient tryptophan alters gut microbiota, increases inflammation, study finds

Augusta University

With age, a diet lacking in the essential amino acid tryptophan, which has a key role in mood, energy level, and immune response, makes the gut microbiome less protective and increases inflammation body-wide, according to a new study published in the International Journal of Molecular Sciences.

In a normally reciprocal relationship that appears to go awry with age, sufficient tryptophan, which we consume in foods like milk, turkey, chicken, and oats, helps keep our microbiota healthy. A healthy microbiota in turn helps ensure that tryptophan mainly results in good things for us like producing the neurotransmitter serotonin, which reduces depression risk, and melatonin, which aids a good night's sleep, the researchers said.

However, in aged mice, after eight weeks on a low-tryptophan diet results in some unhealthy changes in the trillions of bacteria that comprise the gut microbiota and higher levels of systemic inflammation, the researchers said.

Diet has been directly linked to microbiota composition in humans and rodents, they write, and they were able to document impactful shifts. For example, when tryptophan levels are low, the researchers found lower levels of Clostridium sp., the bacterium that metabolizes the essential amino acid enabling production of good products like serotonin in the gut, and a threefold increase in the bacterium Acetatifactor, which is associated with intestinal inflammation.

For the study, researchers led by Sadanand Fulzele, PhD, and Carlos Isales, MD, from Augusta University, explored the relationship between tryptophan, the gut microbiome, and the inflammatory response, in which they fed the aged mice three different diets for eight weeks, diets that were deficient, had recommended levels and high levels of tryptophan.

In the face of low tryptophan, the researchers saw both a direct and indirect impact on the microbiota. These included changes like reduced levels of the bacterium Mucispirillum and Blautia, which play a big role in maintaining microbiota health in humans and animals. Some of these bacteria also have been found to be significantly decreased in patients with Crohn's and colitis, where inflammation can be rampant. Mucispirillum, for example, resists oxidative "bursts" associated with inflammation and produces numerous factors associated with reducing reactive oxygen species and consequently inflammation.

The researchers looked specifically at the largely inflammation-promoting IL-17 and IL-1a as well as IL-6 and IL-27, which can both promote and suppress inflammation, in the blood of mice on a low tryptophan diet. They found significant increases of IL-6, IL-17A and IL-1a and a significant decrease in IL-27, a cytokine which prevents transcription of inflammation-invoking IL-17 and helps do things like increase regulatory T cells in the gut, which suppress inflammation. Conversely, mice on a tryptophan-rich diet had higher levels of the calming IL-27. Generally, the low-tryptophan diet set the stage for inflammation body-wide, the researchers said.

Amino acids like tryptophan are the building blocks for protein production, and proteins are the product our cells produce, which determine their function and ultimately the function of our organs and tissues.