How poo transplants and changes in your gut microbiome might affect your mood

2022-03-06

It took poo donated by strangers for Tony* to finally feel unshackled of his debilitating bipolar disorder.

“It was the first time in 27 years that I could really say I felt normal, which is very weird,” the Sydneysider says.

“It’s a strange feeling to have control which, look, it’s an amazing experience.”

Tony’s story was outlined in a recently published case study ⁠— one of only two such reports so far where people with bipolar disorder found their symptoms drastically improved after they received faecal microbiota transplantation, or poo transplants.

A few months into his six-month course of transplants, administered first in a clinic then at home, Tony’s depressive phases dwindled, and his severe manic episodes stopped altogether.

Jane Dudley experienced a similar shift in her severe bipolar symptoms after opting for faecal transplantation in 2016.

“At that point, I was very, very ill, and being hospitalised a couple of times a year,” says Jane, who is also from NSW and the subject of the other case study, which was published in 2020.

“I was desperate. The level of suffering was just unbelievable.”

Three months after starting her poo transplants, she started noticing the world being brighter and happier.

“Now I’m coming up to five years without serious depression, and September 2017 was the last time I was manic,” she says.

“I don’t think I’d be alive today if I didn’t do [poo transplants].”

In time, and under the careful supervision of their respective psychiatrists, both Jane and Tony went off their medication.

They, and their medical specialists, are not alone in suspecting another person’s poo ⁠— and, more specifically, the microbes within it ⁠— have the power to treat psychiatric conditions.

While poo transplants are nowhere near an approved clinical treatment for mental health disorders, it’s an idea that’s gaining traction in research and clinical circles.

For instance, just last month, a Swiss team reported depression symptoms temporarily improved in two women after they swallowed “crapsules” containing poo from healthy donors.

Anecdotal evidence abounds too, with doctors hearing stories of people with no history of depression who became depressed after receiving a poo transplant from someone ⁠— you guessed it ⁠— with depression.

So how can the activities of microorganisms in our gut affect what goes on up in our skull?

And could we harness the power of “crapsules” to one day help shore up our mental health ⁠— or even mend minds?

More than a gut feeling

Modern science has only relatively recently begun exploring how the trillions of bacteria, fungi and other microbes that dwell in our gut — known collectively as the gut microbiome ⁠— can affect the rest of our body.

The vast majority of studies into what’s known as the microbiome-gut-brain axis have, so far, been done with mice and rats.

In 2004, Japanese researchers reared mice with no microbiome and found they were more stressed than mice with some microbes left in them.

When some beneficial gut bacteria were put back into baby “germ-free” mice, they grew up less stressed than their completely sterile counterparts.

In the years since, research into links between mental health and the human gut microbiome has exploded ⁠— pushed along by studies such as an Irish one in 2016, which found if you put poo from a depressed human into a rat, that rat will start displaying depression-like symptoms.

Researchers from the same institute last year found old mice, aged around 20 months, reversed some age-related cognitive decline if they received a poo transplant from mice who were only a few months old.

Yeah, but what about in humans?

Studies in rodents and case studies like Tony and Jane’s are compelling, but researchers don’t yet know exactly how poo transplants truly work, or why effects vary between people.

We do know our gut and our mood are linked, and it’s more than occasionally feeling butterflies in your stomach.

Studies and surveys have found correlations between gastrointestinal and psychiatric disorders. For instance, one review found 44 to 84 per cent of people with irritable bowel syndrome also had anxiety and/or depression.

And how we mediate our mood through medication can affect how our tummy feels: for some people, anti-depressants and therapy can ease irritable bowel syndrome.

In the past few years, research has moved from association studies, which note that the gut microbiome is different between healthy and people with a disease, and into studies that aim to elucidate exactly how these differences affect health.

There are plenty who would dismiss case studies such as Tony and Jane’s experiences as, well, a load of crap, says Emad El-Omar, a gastroenterologist at UNSW and Microbiome Research Centre director.

“But if you think about the basis of that intervention, demonstrated in [Tony’s] case report, it’s absolutely solid, because there’s nothing more intertwined ⁠— the gut and the brain,” Professor El-Omar says.

“It’s connected in so many different ways.”

Gut bugs and our ‘second brain’

Our gut microbiome’s main role is to help us digest food we normally couldn’t break down. Some of our bacteria chop up long chains of complex carbohydrates into smaller chunks.

These ferment and produce short-chain fatty acids, which we can then use as a source of nutrients.

But all those colonies of microbes lining our gut wall spit out their own suite of compounds or metabolites as they go about their own existence.

These metabolites slip through our intestinal wall, out of the gut, and into the rest of the body.

And they’re not necessarily good for us either.

If nastier microbiome-made metabolites encounter the plethora of immune cells surrounding the digestive system, they can end up fanning the flames of inflammation ⁠— and chronic inflammation is increasingly implicated in conditions such as depression.

They can tinker with our hormones, activating or calming our central stress response system.

Metabolites can even interact directly with the 100-million-odd nerves embedded in the muscular walls of our gut.

This enteric nervous system, sometimes called our “second brain”, communicates directly with the brain in our head.

But complicating matters for researchers trying to tease out how the microbiome affects our brain is how these systems ⁠— immune, hormonal, neuronal ⁠— influence each other, Professor El-Omar says.

“You can’t exclude the immunology from the microbiology, or the physiology from whatever ⁠— they must all work together. They’re all linked up.

“Whatever leaks out of one compartment will affect many others.”

Why aren’t poo transplants used in mental health now?

Your microbiome changes depending on what you eat, where you live, who you live with and the medications you take.

But the quickest way to change up your microbiome is via a poo transplant ⁠— and this is an advantage when it comes to treating severe illness, Professor El-Omar says.

In Australia, faecal microbiota transplantation is only approved to treat intestines overwhelmed by a species of bacteria called Clostridium difficile.

Like any ecosystem, when one species dominates, it can wreak havoc on its environment. But poo transplants work exceptionally well to rebalance the gut microbiome after C. difficile overgrowth, with around a 90 per cent success rate.

Donations come from stool banks, such as Adelaide’s BiomeBank, which carefully screen donors to make sure they’re healthy ⁠— physically and mentally ⁠— so they don’t inadvertently pass anything onto recipients.

But poo transplants and the brain?

Nailing down the right donor for a recipient will be crucial, Professor El-Omar says.

And that’s complicated.

“Which poo are you going to be accepting as a treatment for a particular condition? Is it the right one to drive changes back to normal?

“Plus we still don’t understand why a particular transplant will establish itself [in the recipient’s gut] and be consistently happy in that new environment.”

People might need a couple of top-ups or boosters after their initial round of treatment, he adds.

ABC News, 6 March 2022
; https://abc.net.au