Tryptophan and Age-Related Changes in the Gut Microbiome

Researchers here suggest that reduced tryptophan intake can change the balance of populations in the gut microbiome to favor inflammatory microbes. Diet in late life is often deficient, with consequences that can approach outright malnutrition. It seems unlikely that this is a major issue earlier in life, however, and the gut microbiome exhibits harmful shifts in composition as early as the mid-30s. The influence of changes in the gut microbiome on health may be in a similar range to those of exercise, so it is a topic of growing interest in the research community. Ways to preserve or reset the gut microbiome have been demonstrated in animal studies, such as flagellin immunization or fecal microbiota transplantation. Bringing these and other approaches into human medicine should be a priority, given the comparatively low cost and risk.

With age, a diet lacking in the essential amino acid tryptophan - which has a key role in our mood, energy level and immune response - makes the gut microbiome less protective and increases inflammation body-wide, investigators report. In a normally reciprocal relationship that appears to go awry with age, sufficient tryptophan 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.

But in aged mice, just 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. For example, when tryptophan levels are low, the investigators found lower levels of Clostridium, 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.

The unhealthy changes they saw in the microbiota made researchers also suspect increased release of inflammation-promoting signaling molecules called cytokines, hypothesizing that microbiota changes might induce release of the molecules body-wide. They 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.

When the aged mice resumed a healthy tryptophan intake, some of the unhealthy changes resolved in just a few days. But the reality that just increasing tryptophan did not always correct problems, and that some tryptophan metabolites are actually harmful, provides more evidence that a better option is giving select metabolites early on to help keep the microbiota functioning optimally, rather than attempting a tryptophan rescue.



This Thanksgiving, with a belly full of turkey and a smile on my face, thinking about how much I appreciate this site, Reason and this story in particular, I'll succumb to a tryptophan-induced coma.

Posted by: Thomas Mark Schaefer at July 7th, 2021 8:37 AM
Comment Submission

Post a comment; thoughtful, considered opinions are valued. New comments can be edited for a few minutes following submission. Comments incorporating ad hominem attacks, advertising, and other forms of inappropriate behavior are likely to be deleted.

Note that there is a comment feed for those who like to keep up with conversations.