Thanks for answering our questions. This is such a vital topic for sufferers of IBS and IBD.

Can you give us a bit of background on yourself and what made you interested in the gut biome specifically?

It’s continually fascinating to me, this scientific field. My curiosity started out when I was suffering from debilitating gut symptoms myself. My symptoms eventually resolved, but I had started learning about the gut microbiome and I’ve never stopped. The field is evolving rapidly and now I spend all my time talking to scientists, keeping up with the published studies, and writing about it. There’s so much ‘translation’ work to be done.

The gut-brain axis

What do we currently know about the gut-brain axis? Why is the understanding of this only a recent development?

We’ve known about the gut-brain axis for decades — but the idea that the gut microbiota could influence it is relatively new. Newer and cheaper techniques for DNA sequencing paved the way for the entire field to progress in the past several decades. When scientists gained the ability to get a ‘snapshot’ of the entire microbial community living in a place, they were able to study things like how microbes affect the two-way communication between gut and brain. So far we don’t know much, except that various probiotics might be able to influence aspects of mood and emotional processing.

Causes of IBS and IBD

As far as your knowledge goes, what causes IBS and IBD?

IBD occurs in some genetically-susceptible people — and there are definitely environmental factors too, which haven’t fully been nailed down.

We still don’t know what causes IBS — it remains classified as a functional disorder. But I know scientists who are looking at whether some aspect of the gut microbiota could provide the long-awaited biological measure to diagnose the condition.

The role of the gut biome in IBS and IBD

What’s the role of the gut biome in IBS and IBD?

The gut microbiota is definitely involved in IBD pathogenesis — that much is clear from the science. IBD seems to occur in genetically-susceptible individuals when the gut microbiome and the immune system are at odds. Some outside factors like diet seem to influence the process — like adding gasoline to the fire.

IBS is not as clear — scientists haven’t yet been able to identify a consistent thing that’s different about the gut microbiomes of people with IBS. But there are promising clues that at least some of the symptoms in IBS can be related to the gut microbiota: for instance, because some probiotics are effective at relieving symptoms.

Good and bad gut bacteria

Is there a way to determine directly if the gut biome is “wrong?” What are the conditions which we could, in theory or in practice, test for? Too little bacteria, too much, the wrong kind? Are are some gut bacteria “good” and others “bad?”

Despite scientists’ best attempts, they still don’t know what a ‘healthy’ gut microbiota looks like. So in most cases we also don’t know, by looking at the gut microbiota alone, if something has gone wrong with health. In the future, we might be able to identify gut microbiota ‘biomarkers’ — either specific bacteria or an overall community structure, which could flag conditions like IBD, colorectal cancer, or even something like Parkinson’s disease.

“Good” and “bad” depend on so many things. And they’re virtually impossible to determine for something that lives within such a complex community. For example, bacteria from the genus Bifidobacterium1 are generally considered good for health — but would an adult want their entire gut microbial community to be made up of them? Not at all. It’s more about diversity of the overall community.

Do probiotics work?

Do probiotics work? Is the bacteria integrated into the gut? Does it remain intact or is it overwhelmed by the existing biome?

There’s a common misconception about what it means for a probiotic to work. Scientifically, it means the probiotic has a documented health effect. It’s the end health result that matters, not the probiotic’s ability to ‘colonize’ or integrate into the gut. Because sometimes a probiotic can have great health effects without needing to colonize.

With this in mind, some probiotics work for some conditions, absolutely. There’s gold-standard evidence showing the health effects of different probiotic strains. (We know less about how those probiotics actually manage to achieve their health effects!)

Differences between probiotics

There are many kinds of probiotics, some freeze dried, some requiring refrigeration. What, broadly, differentiates them? How can patients decide between them?

It can be overwhelming to confront all the different probiotic choices! The main thing that matters is the strain (for example, Lactobacillus rhamnosus GG2) — because different strains can have very different health effects. My number one advice is to read up on the condition you have, and find out what probiotic strains are shown to be effective for that condition.

Probiotics for ulcerative colitis

For ulcerative colitis, the VSL#3 probiotic is widely recommended. Are there, then, specific varieties of bacteria that are needed for some conditions, or lacking in those patients naturally? Why would that be?

Yes, it’s because there’s solid scientific evidence that VSL#3 can have beneficial effects. No one knows exactly why — because it’s not necessarily that people with UC are lacking those exact bacteria. But somehow the bacteria initiate a cascade of effects in the body that ends up having a positive effect on the disease. This has been shown in clinical trials.

What ruins the gut biome

What factors can disrupt the gut biome?

Antibiotics are the biggest one. Certain bacteria are wiped out almost immediately. Studies show in some cases the community bounces back, and in other cases it never does.

Infection, too, can disrupt the microbiome. There’s some research going on right now about the onset of IBS after a serious infection — with the hypothesis being that infection can devastate the microbiome and bring on IBS. It’s still just a theory, but scientists are pursuing it.

It’s also becoming clear that a poor diet can disrupt the microorganisms in the gut. A lack of fiber appears to be the biggest thing: it reduces the overall diversity of microbes there and reduces the production of beneficial short-chain fatty acids.

FMT as a treatment

Do you believe that FMT is a treatment for IBS and IBD and to what extent?

I follow the evidence — and right now the evidence shows that FMT is indeed a promising treatment for ulcerative colitis. Not in all cases, but in enough cases to keep investigating it. Some fine tuning of the match between donor and recipient will be required.

FMT is less promising for IBS. Yes, it has a positive effect sometimes — but for any IBS therapy, there’s a strong placebo effect, so we can’t rule out that when FMT works it’s because of this. Maybe the issue is that we need to find ways of sub-categorizing people with IBS, and identifying the one specific sub-category that would respond to FMT without fail. (This is called ‘stratification’.) But we don’t know how to do that yet.

Risk of C. diff infection with IBS and IBD

We have read, and written about, IBS and IBD patients being more likely to contract C. difficile and suffer more complications from it. What causes this risk and, more importantly, can anything be done to mitigate it?

People who take antibiotics in hospital are at risk of C. difficile infection — and people with IBS and IBD may take antibiotics in hospital more than people without these conditions. So it’s not too surprising that they are more affected. The other possibility (yet unproven) is that people with IBS and IBD may already have ‘vulnerable’ gut microbiomes that leave them open to infection with C. difficile.

Some research shows that taking probiotics as soon as you start taking the antibiotics (not afterward) reduces the risk of C. difficile.

Finding FMT donors

Even when a physician is overseeing or consulting for an FMT procedure, patients should still find potential donors from their own lives, that share similar lifestyles and therefore similar gut biomes.

What are some interesting or overlooked factors – and tips – you have encountered that prospecting recipients can keep in mind when searching for donors?

In the scientific trials, donors don’t always have similar lifestyles to the recipient, but the procedures are still effective. I think there’s a lot more work to be done to figure out what makes a good donor!

Super duper healthy is the biggest thing — and someone who doesn’t do shift work and has never received a blood transfusion or gone backpacking in the jungle. As one doctor put it to me: “The ideal donor is someone who’s never done anything interesting.”

Approval for FMT as a treatment in the US

There have been recent steps forward, but when, if at all, do you think FMT could be approved for use with IBS and IBD in countries such as the USA and Canada, and is anything other than additional positive testing required to achieve that goal? What is your opinion about its approval as a natural compound or a drug?

It’s very hard to say. I’d like to think that when the data are convincing enough that FMT is effective and safe, the regulators will approve it for those conditions. But there’s also the squeamishness factor to contend with. I think that will affect the regulatory path.

The smartest people I know say fecal matter should be considered as a ’tissue’ rather than a drug. Then the regulators will address it as such.

Increased frequency of IBS and IBD around the world

We’re seeing increasing diagnosis of IBS and IBD around the world – and presumably, a concomitant imbalance in gut biomes. Can you speculate what is behind this upward trend?

Some have argued our poor Western diet and reliance on processed food, coupled with our over-use of antibiotics, is depleting our microbiomes and increasing the incidence of chronic disease. It may be compounded generation after generation, as mothers pass on a more depleted microbiota to their children.

The future of gut biome treatments

What new treatments do you think will become possible in the future? What can we expect to see as we develop a better understanding of the gut biome?

I’d love to see the ability to manipulate the gut microbiome with precision, not only to provide better treatments for today’s chronic diseases, but also to prevent them in the first place. Dr. Rob Knight talks about a “microbial GPS” — so every day after using the toilet we’d get a read-out of how our gut microbiome is looking, and what it needs to get back on track. I’m so interested to know if one day that will become a reality.
  1. Formerly known as Lactobacillus bifidus. -Ed
  2. A bacterium that was thought to be a subspecies of L. casei, but genetic research proved otherwise. For more on whether there even such a thing as speciation in bacteria, have a look at this recent study. – Ed

Yury Tsukerman