Gastroenterology, Longevity, Medical News

Insufficient tryptophan alters gut microbiota as we age, increases inflammation

The researchers observed large increases in IL-6, IL-17A, and IL-1a, as well as a major reduction in IL-27, a cytokine that serves to activate regulatory T cells in the gut, which block the production of inflammation-inducing IL-17, and a significant drop in IL-27 associated with insufficient tryptophan levels.

A diet deficient in the important amino acid tryptophan, which plays a critical role in our mood, energy, and immune response, makes the gut microbiota less protective as we age and promotes inflammation throughout the body, according to researchers.

Sufficient tryptophan, which we get from foods like milk, turkey, chicken, and oats, helps maintain our microbiome balance in a typically reciprocal partnership that tends to go haywire with age.

According to Dr. Sadanand Fulzele, an longevity researcher in the Medical College of Georgia Department of Medicine, a healthy microbiome helps ensure that tryptophan mainly results in good things for us, such as producing the neurotransmitter serotonin, which reduces depression risk, and melatonin, which aids a good night’s sleep.

However, scientists reported in the International Journal of Molecular Sciences that just eight weeks on a low-tryptophan diet causes some unfavorable alterations in the billions of bacteria that make up the gut microbiota, as well as greater levels of systemic inflammation in older mice. They claim that diet has been directly related to microbiota composition in people and rats, and that they were able to show significant shifts in microbiota composition.

When tryptophan levels are low, the MCG researchers discovered lower levels of Clostridium sp., the bacterium that metabolizes the essential amino acid in the gut to enable the production of good products like serotonin, and a threefold increase in the bacterium Acetatifactor, which is linked to intestinal inflammation.

“We think the microbiome plays an important role in the aging process and we think one of those players in the 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 chief of the MCG Division of Endocrinology, Diabetes and Metabolism. “We also have evidence that the composition of the bacteria that utilize tryptophan changes so even if you eat more tryptophan, you may not use it correctly,” he says.

Fulzele and Isales are co-corresponding authors of a new study that looked into the relationship between tryptophan, the gut microbiome, and the inflammatory response in aged mice. They fed the mice three different diets for eight weeks: one that was deficient in tryptophan, one that had recommended levels of tryptophan, and one that had high levels of tryptophan.

They observed both a direct and indirect influence on the microbiota when tryptophan levels were low. Reduced levels of the bacteria Mucispirillum and Blautia, which are important for human and animal microbiome health, were among the alterations. In individuals with Crohn’s and colitis, where inflammation is common, several of these microorganisms have been reported to be considerably reduced. Mucispirillum, for example, is resistant to oxidative “bursts” associated with inflammation and generates a variety of components that reduce reactive oxygen species and, as a result, inflammation.

Fulzele, Isales, and their colleagues suspected increased release of inflammation-promoting signaling molecules called cytokines as a result of the unfavorable alterations in the microbiota, hypothesizing that changes in the microbiota may cause the molecules to be released throughout the body. They looked at IL-17 and IL-1a, which increase inflammation, as well as IL-6 and IL-27, which may both promote and inhibit inflammation, in the blood of mice on a low tryptophan diet.

They discovered substantial increases in IL-6, IL-17A, and IL-1a, as well as a significant drop in IL-27, a cytokine that helps to boost regulatory T cells in the gut, which inhibit inflammation, by preventing the transcription of inflammation-inducing IL-17. Mice on a tryptophan-rich diet, on the other hand, had greater amounts of the soothing IL-27.

According to the researchers, a low-tryptophan diet laid the scene for inflammation throughout the body. According to Fulzele, when the elderly mice resumed a healthy tryptophan diet, several of the harmful alterations vanished in just a few days. However, the fact that simply increasing tryptophan did not always solve problems, and that some tryptophan metabolites are actually harmful, suggests that giving select metabolites early on to help keep the microbiota functioning optimally is a better option than attempting a tryptophan rescue, according to the researchers.

Their current work is further exploring what a good metabolite mix would look like. “We want to define what products that the gut generates that are good versus bad,” Isales says.

Each person’s microbiota is unique, resulting from our birth moms, and it can vary over time depending on what we eat, breathe, or are otherwise exposed to. It is typically thought of as an organ system that helps us digest food and plays an important part in our immune system and overall health.

Reduced sense of smell, taste, and hunger, as well as related nutritional changes such as insufficient or poor nutrition, might be among the consequences. Furthermore, due of the cumulative effect of toxins we are exposed to, stem cells throughout the body, which are meant to keep us working at a high level by repairing or replacing defective cells, become less effective. Our bodily systems become less efficient, we lose lean muscle mass and acquire fat, which generates inflammatory chemicals, and our weight moves around so we store more of that fat in and around our abdominal area, which is the most inflammatory and deadly. Because fat burns calories less efficiently than lean muscle, our metabolism slows, which can lead to weight gain.

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

Isales and Fulzele agree that the gut microbiota is a significant modulator of chronic disease conditions like impaired digestive health, declining cognitive function, and a compromised immune system, and that this “unnatural” aging process is linked to chronic disease conditions like impaired digestive health, declining cognitive function, and a compromised immune system.

“We accept as normal that your organs stop working as well. We accept that the ejection fraction of your heart drops as you get older. We accept that your brain function decreases as you get older. We accept as normal what is not normal,” says Isales, who along with Fulzele and their other colleagues in the MCG Center for Healthy Aging want to help reestablish for most of us what they consider the ability to live a significantly longer, and healthier life.

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