If you’ve been reading my blog for any length of time, you’ve likely heard me talk about short-chain fatty acids (SCFAs). SCFAs, particularly butyrate, are often depleted in states of gut dysbiosis and chronic disease.
But SCFAs are just one of three major categories of gut metabolites. The other two categories – tryptophan metabolites and bile acids – play equally important roles in maintaining gut health. And it’s about time that I featured them on the blog!
In this first article, I’ll be covering what tryptophan is and introducing the three major pathways of tryptophan metabolism. In the next few articles in the series, I’ll go into each pathway in more detail and discuss the importance of balance among the three pathways. I’ll also talk about how this balance becomes skewed in chronic disease states, and of course, how we might use this information to restore balance and support gut and overall health. Let’s dive in!
What is tryptophan?
Meet tryptophan. Tryptophan is an amino acid – one of the many building blocks of protein in our body.
Tryptophan is also an important precursor to a number of other compounds in the body, including:
- melatonin, a hormone that regulates sleep-wake cycles
- niacin (vitamin B3), a nutrient that helps the body turn food into usable energy, and
- serotonin, a neurotransmitter that plays a role in mood regulation and gut motility
As we’ll see, tryptophan is also a precursor to many other metabolites in the gut.
Getting adequate tryptophan: the importance of protein for gut health
Tryptophan is an essential amino acid, which means our body can’t synthesize it and we need a regular supply in our diet.
So where do we get tryptophan? Tryptophan can be found in most proteins, so a deficiency of tryptophan is most often due to inadequate dietary protein intake. In general, animal proteins tend to have higher amounts of tryptophan than plant proteins. While tryptophan can be taken in supplement form, it is best to get it as part of the complete protein in whole foods.
Sources of tryptophan include:
- Meat, fish, and poultry
- Dairy products
- Beans and legumes
- Sesame seeds
- Dark chocolate
Low tryptophan intake has been associated with depression, anxiety, poor mood, lower quality sleep, reduced visual cognition, and impaired learning and memory.1–4 It may also alter the gut microbiome and impair gut immunity.5
The three major fates of tryptophan in the gut
While most tryptophan is absorbed in the small intestine, some of it continues on to the large intestine, where it can be acted on by microbes and host cells.6 There are three major fates of tryptophan within the gut:
1) The indole/AhR pathway. Gut bacteria directly convert tryptophan to indoles and related molecules. Like a lock and key, some of these indole molecules bind to the aryl hydrocarbon receptor (AhR) on the surface of cells throughout the gut and other organs. This triggers a wide range of responses that promote gut homeostasis. The activity of this pathway depends on diet and the composition of the microbiota.
2) The kynurenine pathway. Some tryptophan is taken up by gut epithelial cells and immune cells, where it is converted by an enzyme called IDO1 into kynurenine. Kynurenine can be further metabolized to other molecules, such as quinolinic acid, which has neurotoxic effects. The activity of this pathway is increased by stress, inflammation, or infection.
3) The serotonin pathway. Tryptophan is also taken up into gut enteroendocrine cells, which is then converted to the neurotransmitter serotonin via the enzyme TpH1. Serotonin in the gut regulates gut motility, secretion and absorption, and plays a role in gut-brain signaling. The activity of this pathway is affected by fasting, diet, gut infection, and certain microbes.
The key, of course, is balance. In a healthy gut, these three pathways are balanced, resulting in optimal gut barrier function, motility, immunity, and neurological function.
Altered tryptophan metabolism in chronic disease
In chronic diseases, however, the balance of the three pathways above appears to be skewed, resulting in impaired gut function and systemic implications.
Here are just a few conditions that are characterized by altered tryptophan metabolism:
- Inflammatory bowel disease7
- Irritable bowel syndrome8
- Metabolic syndrome10
- Cardiovascular disease11
- Inflammatory skin conditions13
- Allergies and autoimmunity14,15
- Celiac disease17
- Multiple sclerosis18
Moreover, more and more studies are showing how we can modulate the microbiome or tryptophan metabolism to influence clinical outcomes in disease states. Diet and lifestyle factors, along with certain probiotics, plant compounds, and micronutrients can all be used to shift the balance of tryptophan metabolites. I’ll be covering many of these throughout this series.
In part 2, we’ll be taking a deep dive into the indole/AhR pathway and its implications for gut immunity, gut barrier function, and vagus nerve activity. Stay tuned!