For the past few years I’ve been researching and immersing myself in the inner workings of the human microbiome.
I’ve suffered from an upset stomach for most of my life. And with my patience thinning (as a result of having to orientate my life around the problem) — I wanted to get to the bottom of what was causing it, and find some relief.
If you’ve suffered with a similar condition, I’m sure you can empathise with just how much of a detrimental impact it can have on your quality of life. It takes up a lot of mindshare.
After meeting with pretty much every single one of London’s best qualified consultants, nothing seemed to work. I had given blood, tried out various diets, been poked and prodded for months. With the only practical advice received being to take Imodium and try meditation.
I wanted to know why none of these doctors could diagnose or treat my problem correctly. And if they couldn’t diagnose or treat me, how many others were in a similar boat?
I started to learn everything I could on the topic, to at least try and find some informed direction to head. I want to share some of my insights in this post.
Why gut health is important
The gut microbiome is a vast ecosystem of organisms such as bacteria, yeasts, fungi, viruses and protozoans that live in our digestive pipes, which collectively weigh up to 2kg (heavier than the average brain).
It is increasingly treated by scientists as an organ in its own right. Each gut contains about 100 trillion bacteria, many of which are vital, breaking down food and toxins, making vitamins and training our immune systems.
Over the past decade, research has suggested the gut microbiome might potentially be as complex and influential as our genes when it comes to our health and happiness.
As well as being implicated in mental health issues, it’s also thought the gut microbiome may influence our athleticism, weight, immune function, inflammation, allergies, metabolism and appetite.
How the gut impacts the brain
It’s hard to picture how these tiny microbes in our gut contribute to our day-to-day cognition and brain function.
In a book called “The Good Gut” the authors describe how a group of researchers put normal and microbe free mice through some memory tests.
First, the mice were given five minutes to explore two new objects. A small smooth ring, and a large chequered ring. Then the objects were removed for twenty minutes. After that, the large chequered ring, and a new object, a star shaped cookie cutter, were put in the cages.
Predictably, the mice with the normal microbiota checked out the cookie cutter and paid less attention to the chequered ring because they already knew what it was.
The microbiota free mice, explored the new cookie cutter, but spent just as much time checking out the old object – the chequered ring. It seemed that these mice had completely forgotten an object they had just seen twenty minutes earlier.
The forgetfulness of these mice may be explained by the fact the microbe free mice have lower levels of BDNF. Brain Derived Neurotrophic Factor, is a powerful protein important for learning and memory. It stimulates the production of new brain cells and strengthens existing ones. Low levels of BDNF are linked to depression and anxiety.
Another study has shown that behaviour and anxiety within mice depended on which microbes were living in their gut.
They switched the microbiota between two groups of mice and measured how long it took them to jump off an elevated platform within a cage. As you would expect the “anxious” mice became “confident” and the “confident” mice became “anxious”.
The microbiota switch also made the newly confident mice have more levels of BDNF. The changes in microbiota not only made observable changes in behaviour, but in brain chemistry as well.
There’s all kinds of chemistry going on in the gut that can affect the brain. There’s even research identifying which specific microbes produce which neurotransmitters.
For example, it’s estimated that 90% of our serotonin is produced in the gut, and it’s been found that at least some of this serotonin is produced by these four microbes: Candida, Streptococcus, Escherichia, Enterococcus.
Lactobacillus and Bifidobacterium — these two microbes produce gamma-Aminobutyric acid (or “GABA”) – our chief inhibitory neurotransmitter which has relaxing and anti-anxiety effects. Bacillus and Serratia — these two produce our motivational neurotransmitter, dopamine.
So we basically have this huge mass of little drug factories sitting in our gut pumping out different substances that affect our brain.
In fact the gut and its microbes appear to affect the brain so much that preclinical research in rodents suggested that certain probiotics have antidepressant and anti-anxiety effects.
It doesn’t take a scientist, to find the literature on the potential of probiotics when reading about gut problems.
The effectiveness of which the scientific community is still very much divided on.
A meta-analysis — that is a study of the data of many independent studies to determine overall trends — published in the journal Gut Microbes in 2017 found the effects of probiotics were “evidence-based” only in preventing specific forms of diarrhea and respiratory tract infections. A more recent article published in Nature Medicine also included inflammatory bowel disease and irritable bowel syndrome on the list of conditions for which probiotics have shown therapeutic efficacy, but the authors rejected the notion they prevent respiratory infections.
For other health claims, like alleviating depression or preventing dermatitis, the data is just not there. The various trials that have tried to assess these claims have produced contradictory results, making evaluations of probiotics difficult.
Even for the bacteria proven to be useful, their benefits might not be shared by everyone. People respond differently to probiotics — for some, their microbiome is amenable to new bacteria, while for others it isn’t. It’s a reminder that our internal ecosystems are quite complex.
Personally, I’ve a big believer in the potential for probiotics, and I think the data will catch-up eventually. Over the past 5 years I’ve taken a supplement called Symprove. And it’s just about the only thing that makes my chronic stomach difficulties subside. So there’s obviously something working.
I think we can go one step further
As we know, microbiomes are really complicated, and everyone’s microbiome is different. So every person’s needs are different.
Experts agree probiotics should be sold to treat specific conditions and not in the current “one size fits all” format.
So, what if we could design microbes to target specific tissues and cells rather than your whole body, avoiding preventable side effects, bringing probiotics to a whole new level?
This is where I think machine learning and synthetic biology could engineer better probiotics.
This is exactly what several companies are doing by leveraging synthetic biology.
Since the microbiome is involved in so many health processes, it’s no surprise that synthetic biologists are creating “living medicines” to tackle significant health problems through the microbiome. Many companies are starting in the gut — home to the most diverse ecosystem of microbes found in the human body.
Zbiotics is the company that successfully developed the world’s first genetically engineered probiotic. Their bioengineered probiotic bacteria has been designed to increase the production of the chemical factories (enzymes) in your body that break down a toxic chemical byproduct of alcohol in your gut. In other words, they’ve invented a hangover cure — but you have to ingest it before or during drinking.
But hangovers aren’t exactly a disease. Synlogic is targeting phenylketonuruia, a rare genetic disorder that prevents patients from breaking down an amino acid called phenylalanine. They’re also developing cancer therapeutics that work without persisting or accumulating in the body. Synlogic believes that living medicines could be used as anti-cancer agents, activating your own body against cancer cells, and potentially improving the effectiveness of other immunomodulatory treatments. Personally, I love Synlogic’s strategy of going after an orphan drug designation for phenylketonuria because it’ll prove that living medicines can work.
Another example is ActoBio, they’ve developed a probiotic delivery platform using the same bacteria that make cheese and other delicious foods. In this case, these bacteria have been engineered to produce a treatment for diabetes and deliver it directly to the body’s sites in need. Using this synthetic biology, ActoBio is able to target tissues more precisely, challenging conventional diabetes treatment such as pills or injections.
What is clear though is that microbes living in and on you are just as much a part of your health as your own cells. And these tiny organisms play dramatic and important roles in your health.
I think over the next few years we’re going to make exciting discoveries in the usefulness of probiotics — with underlying data to support. I also think probiotics will be more targeted through a machine learning approached coupled with better and more frequent sampling.
It’s one area that I’m thinking of dedicating a good portion of my time too over the next decade.