Insomnia and the Gut Microbiome

A casual research proposal

What can synthetic biology do about this?

🦶The basics

Sleep helps us repair our bodies, recover energy, perform well the next day, and so on. Lack of sleep has been linked to a higher risk for certain diseases and medical conditions, like type 2 diabetes, high blood pressure, heart disease, stroke, poor mental health, and early death.

Circadian rhythm

Another kinda fancy word. The way I see it, the circadian rhythm is an abstract concept to refer to all the body organizing its schedule to do different activities. Every 24 hours the cycle is repeated. In other words, it’s how we measure the “day” in our bodies.

Representation of the circadian rhythm and its relation with sleep

More cycles

Just to know more, I think it’s also interesting to know about the different stages that we go through when we sleep, and what happens in each one of them.
At first, we can divide the phases into 2: non-rapid eye movement (NREM) sleep, and rapid eye movement (REM) sleep. The first phase is also divided into 3 stages. Let’s take a look into what happens in each of these:

🎯 The Challenge

Sleep disorders

It’s normally the deregulation of this circadian clock that causes the difficulty to sleep for some people.
According to general estimates, 10–30% of adults live with some form of insomnia, which is defined by a persistent difficulty falling or remaining asleep despite the opportunity and motivation to do so.
Chronic insomnia occurs when these symptoms are present at least three times per week for at least three months. Insomnia lasting less than three months is known as short-term insomnia.

WEF survey

Conventional Pills

Medications are prescribed 95% of the time when treating this condition. However, do they really work?

🧠 The Science


Talking about light… You may have heard about N-acetyl-5-methoxytryptamine before (AKA melatonin). It’s a key player when it comes to sleep. When people have trouble producing it naturally, they need to take it as a supplement.

  1. Neurons in the ventrolateral SCN can activate their genes according to light input
  2. When the retina receives light, ventrolateral neurons relay this information throughout the SCN allowing synchronization of the circadian rhythm
  3. SCN sends information to the pineal gland to modulate body temperature and production of hormones such as cortisol and melatonin
Melatonin creation process

In the gut

Despite all the chemical reactions happening in the brain to go from tryptophan to serotonin and finally have melatonin, the truth is that more than 90% of serotonin is found in the gut. Why though?

Correlation between gut microbiome and interlukin-6

*How* exactly are gut microbiota influencing sleep?

💡The Solution?

Before actually coming up with a solution to insomnia, we need to be sure of how these mechanisms work. What are the precise characteristics that allow microbes to have this correlation with sleep?

Living medicines

Credits to GROW by Ginkgo


Probiotics are live microorganisms that have as a purpose to provide a health benefit to the person taking them. They can be found in food, and sometimes in beauty products as well.
It is most common to see organisms such as bacteria when referring to this topic. At the same time, some of the most common groups are Lactobacillus and Bifidobacterium.

  1. Media formulation
  2. Fermentation
  3. Centrifugation (to separate the probiotic strains from the metabolites)
  4. Cryoprotection
  5. Freeze drying
  6. Dosage
  7. Packing
  8. Quality control
  • Probiotic commercialization should be run in parallel with clinical trials, to avoid studying an uncommercializable strain
  • Once high-quality probiotic bulk has been produced, the strain needs to be incorporated into consumer products


This said, the final hypothesis is that by genetically modifying bacteria to produce tryptophan or serotonin at a constant rate by sensing the metabolites produced by the host before they sleep, the bacteria will diffuse those substances into the vagus nerve and the pituitary gland will have the necessary substrates to produce melatonin: the host could be able to sleep.

💭 Last thoughts

The microbiome revolution is taking place right now with hundreds of research studies being done to know how the trillions of microbes can communicate with other parts of the human body.
There is no doubt that they somehow correlate with sleep. However, the assumptions that could now be made, are possibly not that accurate. Thus, it is essential to continue studying this topic at a more specific level. This is, for specific bacteria species, and in the context of the production of specific substances.


Ambitious teenager building innovative projects with Synthetic Biology and Artificial Intelligence

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