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The gut-brain axis: New therapeutic approaches and R&D

The gut-brain axis is the term used to describe the close two-way relationship between the gut and brain. The two organs communicate with each other via hormones, neurotransmitters and nerve signals, and this communication is essential for maintaining health. The gut-brain axis has been implicated in a variety of conditions, including obesity, anxiety and depression.

Before I begin, a disclaimer: I am not a medical doctor. So nothing I write below is medical advice in any sense (I’m also not a lawyer, so I don’t know how to write this in proper lawyerese, but you get the idea).

I explored the topic starting out from the following search (click on the image to see an overview snapshot):

As you can see when you look at the “science publications” section of the results, there’s been a substantial increase in publishing activity in gut-brain axis (cf. red arrow; click on the image to see it in full size):

Science publications on gut-brain axis have increased substantially over the past years.
Science publications on gut-brain axis have increased substantially over the past years.

But before I explore the R&D, some companies first. Specifically, I looked at companies that received venture funding. The chart below, from the “venture capital” section of my results, shows that some companies received multiple rounds (Kallyope and Axial; click for full size):

Some venture capital fundings in the area of gut-brain axis. Screenshot from Mergeflow.
Some venture capital fundings in the area of gut-brain axis.

Kallyope: A systems biology platform company

Kallyope presents itself as a platform company. I understand this to mean that while they work on specific therapies targeting specific diseases, as shown in their pipeline…

Kallyope's therapy pipeline, image from Kallyope's website.
Kallyopes therapy pipeline image from Kallyopes website

…they want to build an entire technology platform, involving sequencing technologies, optogenetics, and others. While they don’t explicitly say this (not to my knowledge at least), this sounds as though they might at some point operate platform business models as well. Perhaps comparable to what Ginkgo Bioworks does in a different domain with their synthetic biology platform.

In their latest funding round, Kallyope raised $236M Series D from Mubadala, The Column Group, Alexandria Venture Investments, Casdin Capital, Euclidean Capital, Illumina Ventures, Lux Capital, Polaris Partners, Two Sigma Ventures, StepStone Group, and others.

Axial Therapeutics focuses on developing small molecule drugs to treat neurological disorders. This includes treating irritability in children with autism, for example. According to Axial’s website, there are currently limited treatment options for such conditions. But the effects of autism-related irritability can be substantial, including aggression and self-harm.

Why small molecules? Again, I’m not a medical doctor or a microbiologist. But from what I read, it’s because…

  • …because of their low molecular weight and relatively simple structure, their pharmacokinetic behavior is more predictable, which means it’s easier to develop dosing protocols;
  • …they are easier to manufacture;
  • …they are more stable and can therefore be administered orally;
  • …they are more affordable

I paraphrased the above from this paper:

What are the drugs of the future?

In 2021, Axial raised $37.25M Series C. Investors include OneVentures, the University of Tokyo Innovation Platform Company (UTokyo IPC), Autism Impact Fund, Corundum Systems Biology, Longwood Fund, Seventure Partners, Taiho Ventures, and Domain Associates.

Enterin: A compound first found in sharks may work against neurodegenerative diseases

Enterin develops treatments for neurodegenerative disorders such as Parkinson’s Disease.

Underlying the work at Enterin is the following hypothesis: There is an overproduction of the protein alpha-synuclein. As a consequence, alpha-synuclein clogs up the substantia nigra (= brain region affected in Parkinson’s).

Now, Enterin’s lead compound, called ENT-01, is based on squalamine, which was originally found in sharks. Squalamine can prevent this accumulation of alpha-synuclein.

You can watch the video below to hear Enterin co-founder Michael Zasloff explain this in more detail:

Enterin co-founder Michael Zasloff describing how Enterin’s compounds work.

In 2017, Enterin raised $12.7M Series A from New Ventures III and other investors that were not disclosed.

Next, some R&D.

Gut-brain axis R&D is gaining momentum

I mentioned this already, gut-brain axis R&D has been gaining momentum. You can see this in the graph below:

Gut-brain axis science publications have been going up. Screenshot from Mergeflow.
Gut brain axis science publications have been going up

Not surprisingly, publication activity in gut-brain axis is almost perfectly correlated with publication activity in microbiome:

Science publications in "gut-brain axis", "microbiome" (secondary axis), and "gut-brain axis AND microbiome". Data from Mergeflow.
Science publications in microbiome and gut brain axis

R&D on mechanisms underlying the relationship between diet and migraine

Since even attempting anything like a comprehensive overview in a few paragraphs is not possible, I decided to pick a subtopic I found interesting. In the “science publications” section of the gut-brain axis results overview, I noticed an article, “Gut microbiota and migraine”, that just came out:

Most recent (April 2022) science publications on gut-brain axis. Screenshot from Mergeflow.
Most recent April 2022 science publications on gut brain axis

In order to zoom in a bit more, I used Mergeflow’s molecule identification algorithm, which detects names of chemical compounds in texts. Here is a network graph that shows which compounds are mentioned in common contexts (stronger lines -> more common contexts; click on the image to see it in full size):

Network graph showing what chemical compounds are mentioned in common contexts, in science publications on gut-brain axis and migraine. Screenshot from Mergeflow.
Network graph showing what chemical compounds are mentioned in common contexts in science publications on gut brain axis and migraine

For my purposes here, I focused on the middle network component, the relationship between vitamin D and serotonin. Here is one article from which Mergeflow extracted this relationship:

Gut-brain Axis and migraine headache: a comprehensive review

According to this article, it could be that “migraine may be improved by dietary approaches with beneficial effects on gut microbiota and gut-brain axis including appropriate consumption of fiber per day, adhering to a low glycemic index diet, supplementation with vitamin D, omega-3 and probiotics as well as weight loss dietary plans for overweight and obese patients.”

This article was written by:

Florian Wolf

Florian Wolf

Florian is founder and CEO at Mergeflow, where he is responsible for company strategy and analytics development at Mergeflow. Previously, Florian developed analytics software for risk management at institutional investors. He also worked as a Research Associate in Computer Science and Genetics at the University of Cambridge. Florian has a PhD in Cognitive Sciences from MIT.

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