As we age, a diet that lacks the essential amino acid tryptophan – which plays a key role in our mood, energy levels, and immune response – makes the gut microbiome less protective and increases inflammation throughout the body, researchers report.

In a normally two-way relationship that seems to go wrong with age, enough tryptophan that we consume in foods like milk, turkey, chicken, and oats helps keep our microbiota healthy.

A healthy microbiota, in turn, helps tryptophan mainly lead to good things for us, like the production of the neurotransmitter serotonin, which reduces the risk of depression, and melatonin, which supports a good night’s sleep, says Dr. Sadanand Fulzele, an aging researcher at the Medical College of Georgia Medical School.

But in old mice, just eight weeks on a low tryptophan diet results in some unhealthy changes in the trillions of bacteria that make up the gut microbiota and increased systemic inflammation, they report in the International Journal of Molecular Sciences.

Diet has been directly linked to the composition of the microbiota in humans and rodents, they write, and they have been able to document effective changes.

For example, when tryptophan levels are low, the MCG researchers found lower levels of Clostridium sp., The bacterium that metabolizes the essential amino acid and enables the gut to produce good products like serotonin, and a three-fold increase in the bacterium acetateifactor, which is related to Intestinal inflammation.

“We believe that the microbiome plays an important role in the aging process and we believe that one of those actors in aging is tryptophan, which produces metabolites that affect every organ function,” says Dr. Carlos M. Isales, Co-Director of the MCG Center for Healthy Aging and Head of the MCG Department of Endocrinology, Diabetes and Metabolism. “We also have evidence that the makeup of the bacteria that use tryptophan is changing. Even if you eat more tryptophan, you may not be using it properly, ”he says.

Fulzele and Isales are joint corresponding authors on the new study, which further explores the relationship between tryptophan, the gut microbiome, and the inflammatory response by feeding the aged mice three different diets for eight weeks – diets that were deficient, recommended levels, and high tryptophan levels .

In view of the low tryptophan content, they saw both a direct and an indirect influence on the microbiota. These included changes such as reduced levels of the bacteria Mucispirillum and Blautia, which play a major role in maintaining the health of the microbiota in humans and animals. It has also been found that some of these bacteria are significantly reduced in patients with Crohn’s disease and colitis, where inflammation can be rampant. Mucispirillum, for example, resists oxidative “bursts” associated with inflammation and produces numerous factors associated with the reduction of reactive oxygen species and, consequently, inflammation.

It was the unhealthy changes they saw in the microbiota that also led Fulzele, Isales, and their colleagues to suspect increased release of pro-inflammatory signaling molecules called cytokines, and suggested that changes in the microbiota caused the molecules to be released throughout the body could. Specifically, they examined the largely pro-inflammatory 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 diet low in tryptophan. They found significant increases in IL-6, IL-17A and IL-1a and a significant decrease in IL-27, a cytokine that prevents the transcription of inflammatory IL-17 and helps increase regulatory T cells in the gut that suppress inflammation. Conversely, mice on a diet rich in tryptophan had higher levels of the sedative IL-27.

In general, the low-tryptophan diet set the stage for inflammation throughout the body, investigators say.

When the aged mice resumed healthy tryptophan intake, some of the unhealthy changes disappeared in just a few days, Fulzele notes. But the fact that simply increasing tryptophan did not always correct the problems, and that some tryptophan metabolites are actually harmful, provides more evidence that giving selected metabolites early is a better option for the microbiota to function optimally rather than attempting a tryptophan rescue. say the investigators.

Her current work further explores what a good mix of metabolites would look like. “We want to define which products the intestine produces that are good or bad,” says Isales.

Each person has a unique microbiota that originates from our birth mothers and can change over time depending on what we consume, inhale, or otherwise exposed to. It is widely viewed as an organ system that enables us to digest food and plays a key role in the immune response and our overall health. The microbiota should also help protect us at any age from the harmful effects of environmental factors and the consequences of aging itself, says Isales.

This damage can include a decreased sense of smell, taste, and appetite and related dietary changes such as inadequate or poor nutrition. Also, throughout the body, stem cells designed to keep us functioning by repairing or replacing dysfunctional cells become less functional due to the cumulative effects of toxins to which we are exposed. In a little vicious circle, our body systems become less efficient, most of us lose lean muscle and gain fat, which produces inflammatory molecules, and our weight shifts so we store more of that fat in and around our abdominal area – it tends to to be the most flammable and deadliest. Fat also burns fewer calories than lean muscle, so our metabolism slows down, which in theory should slow aging, but most of the time it can’t in the face of other changes.

“Basically, your immune system is dysregulated, you have persistent inflammation from damaged tissue through the processes that normally keep you healthy,” says Isales, as chronic inflammation can replace the classic episodic immune response that fights infection and enables healing.

What Isales calls this “unnatural” aging process has been linked to chronic disease conditions such as impaired digestive health, declining cognitive function, and a weakened immune system, and he and Fulzele agree that the gut microbiota is a major modulator of these.

“We accept as normal that your organs no longer function either. We accept that your heart’s ejection fraction decreases as you age. We accept that your brain function decreases as you age. We accept what is not normal as normal, ”says Isales, who, together with Fulzele and her other colleagues at the MCG Center for Healthy Aging, want to help ensure that most of us have the opportunity to lead a significantly longer and healthier life again .

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


The research was funded by the National Institute on Aging.

Read the full study.


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