Probiotics -seeds of change, or unnecessary chimpanzees?

AKA What I say when people ask me about Yakult.

chimpintundra

“Probiotics -what do you think of them?” 

I get asked this quite a lot, when I talk about antibiotics, gut bacteria, and our own microbial community, or ‘microbiome’,  in general.

So first up, let’s just say, I love Microbiomes. I think the whole area is fascinating, I’m lucky enough to work in the area,  and I firmly believe a better understanding will transform how we see health, and how we treat our patients.

I think…we’re not quite there yet.

As I’ve heard it described many times, Microbiome science is generally still in the ‘cataloguing’ stage. We’ve just been given the tools for the first time to go and explore these incredibly complex ecosystems, previously hidden from our eyes. And we’re going into Amazon rainforest, Appalachian plains, and snowy mountains, and we’re cataloguing and counting everything we find there.  It’s a wonderfully exciting time.

rainforest-356187_960_720

We’re finding that some people have incredibly diverse guts, full of  rarely-seen species – (Amazon rainforest guts) – and others maybe have guts more like Siberian tundra – more sparse, fewer different species (that we can see).

Some scientists are finding they can correlate the presence of certain species with health conditions. You might say guts of patients with diabetes are less likely to contain oak trees, or guts of obese patients have far more monkeys than ants, compared to those of normal bodyweight.   Great.  This is all interesting stuff.

What can we do with this, and how does it relate to probiotics? 

I guess the current generation of probiotics are largely sold on their ability to give you ‘healthy bacteria’. There are even companies which measure your microbiome, and prescribe your own ‘personal yakult’ based on what bacteria you appear deficient in. I know there’s quite a probiotic literature, but to date, is there a probiotic that works convincingly enough that I would recommend my patients? Not yet.

It may be that these probiotics work brilliantly for many people. But with regards the promised ability of probiotics alter the microbiome and improve health? Or the promises to replace ‘missing’ gut bacteria? For me it’s all a bit…chuck in and hope.

Certainly when people study the effects, they find that the probiotic bacteria can be detected in gut samples, but generally only for as long as someone keeps taking the probiotic. Stop taking it, and they’re gradually lost. It seems nothing is quite as good at surviving in your gut as your own gut bacteria.  (And it’s also worth noting that it appears you often have to give the probiotics with a large dose of sugar to even get them to the gut in any fit state).

It’s a bit like having a gut like Siberia, and wanting a gut like an Amazon Rainforest. Maybe you note that a key difference is that there are thousands of monkeys in the Amazon.  

I worry the current generation of probiotics are a bit like taking 10,000 monkeys a week and chucking them in Siberia (maybe you even bring in a few cratefuls of bananas as well)  and expecting your gut to turn into Rainforest.  Yes, you’ll detect monkeys, but they aren’t going to last long…and your gut is just Siberia with a lot of unhappy (and ex-)monkeys.

capuchin

Maybe some probiotics are better than this. Maybe our guts aren’t quite as different as the tropics and the Antarctic, and sometimes we’re  getting monkeys to nice forests with a monkey-deficiency. Or  possibly they’re more like adding earthworms from Scottish farms to English gardens. Maybe they do improve things, in ways that haven’t currently been seen in trials to date. The point is, we really don’t know.  But the whole thing does make you really think about the reductionist view that adding a single bacterial species is somehow going to create a significant change.

In the end, I think to begin to understand Microbiomes, you have to think Ecosystems, and Ecology.  Complex  , dynamic, highly variable, each element codependent on hundreds of others.   There’s a wonderful paper visualising the mouth (and  tooth) microbiome, showing ‘branches’ of Corynebacterium, and ‘leaves’ of Streptococci.. (covered really nicely by Ed Yong here). Microbiomes aren’t  just a mulch, a ‘bacteria soup’, but a highly structured, organised network, just like the forest floor to the forest canopy, each with it’s own ecological niches and species.

oralmicrobiome

From: Welch et al, Biogeography of a human oral microbiome at the micron scale, PNAS 2015

At the moment, the real success in the field of microbiome therapy is repopulating the gut bacteria in patients with recurrent Clostridium difficile infection, using ‘faecal transplants’. This uses gut bacteria from healthy patients to cure those whose guts are overrun by the C. diff. bacteria. If you like, we’re taking a whole section of Amazon rainforest- soil, plants, insects, monkeys, all,  and chucking it into an area depleted of diversity, and overrun by one type of invasive species. The area might not turn into Amazon, but it seems for now it’s got a better chance of recovering some balance than just blasting the area with pesticide again. Some interesting studies are suggesting that just the spores of bacteria from healthy individuals might be enough – rather like ‘re-seeding’ (nicely covered by Jon Otter at IPC here.)

The slight problem with this approach is that we don’t really know what we’re putting in. We might be adding a whole load of earthworms and shrubs (great), but we might be introducing a few new species which aren’t so good for that particular area, altering the way it functions long term. There’s an interesting case report of a normal body weight recipient becoming obese after receiving gut bacteria from an obese donor, and this effect seems to be demonstrable in mice as well.   It certainly makes many Doctors nervous, to be using something when they don’t even know quite what it contains, but for now the benefits are clear, large, and stand up fairly inarguably in well-conducted clinical trials *in the specific setting of recurrent C. diff. infection*.  So they get the go ahead.

But many, I think, see faecal transplants as a temporary measure, whilst we really work this whole gut thing out. Studies like RePOOPulate are seeking to create a known mix of bacteria to perform this function, without the concern about unknown additions and effects. And what, so far, I believe it being found is that it’s incredibly difficult! I mean, imagine trying to recreate the ingredients required to start a mangrove swamp… a coral reef…

There’s also a lot of interest in dietary advice to ‘change your microbiome’. Absolutely, a healthy diet will encourage a healthy microbiome. But again, I think we’re a long way from being able to pinpoint specific foods and definite effects. It’s probably broadly sensible and scientifically valid to say that eating fibre, vegetables, and less processed food, will improve the health of the microbiome. But beyond that, I think most people who study the subject in detail will tell you that it’s honestly impossible to tell at this point what foods cause what effect.

So for now, if people are promising that they have a miracle cure for your chronic health condition with (usually expensive) probiotic supplements, or specific dietary advice beyond a generally healthy diet, I’d say that probably they’re talking guesswork, dressed up as knowledge.  If that’s enough for you, then ok. If it helps you eat a healthier diet, and feel better, and it doesn’t drain your wallet of money required for important things, then fair enough.  But do ask yourself if you think they’re (often well-meaning) monkey sellers, standing to profit from your weekly order of wholly unnecessary chimpanzees.

So probiotics – I think we’ll get there, and quite soon. Once we’ve done a bit more work understanding what’s actually going on in the tiny world that lives on us, and with us.

rainforest

 

 

 

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Edit: Just to add a bit of probiotic evidence – There appears to be a moderate amount of evidence that using probiotics may reduce the likelihood of developing C. diff. infection in patients taking antibiotics, in settings where there’s quite a high incidence of C. diff. In the UK, where there isn’t a lot, it’s almost impossible to say. You’d probably end up treating a huge number (thousands and thousands) of people with unnecessary probiotics, to maybe prevent a few cases. And we don’t really know which patients would benefit most, or which probiotics are best. So again, I’m perfectly happy for people to take them if they want, but I wouldn’t give formal advice to take them at this point.  (and a few typos)

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Notes:

I think it’s really fun to read about microbiomes, and research is throwing up some incredibly exciting stuff, but every finding needs to be taken with both interest and caution, or risk ‘overhyping the microbiome’. I know (from personal experience) it’s so easy to just get over-enthusiastic and not realise (or not make it clear) when you’re moving from solid ground to valid hypothesis, to speculation based on incomplete, though promising, evidence. It’s made me a lot more cautious about how I talk about the subject.  I think even eminent scientists in the field can fall guilty  –  it’s really hard when you’re talking about something that’s so interesting, and new.

So overall if you want to read more about microbiomes, from those who can keep their feet on the ground but not be lost in the skepticism, I’d recommend reading more from Scientists like Jonathan Eisen, Jack Gilbert and science writer Ed Yong.  Basically, if they’re being clear, and interested, but skeptical, that’s probably a good thing.  In fact I’m going to go with Jonathan Eisen, quoted just recently on an article about ‘microbiome mis-selling‘ –

“If people are selling something when they make a claim [..]-If people make claims about conspiracies of scientists and doctors hiding the truth […] If people don’t cite any scientific studies but instead cite anecdotes and testimonials and self-written books […] If people have a history of making misleading claims […] then question what they are saying.  A lot.”

Note #2:

I’m a big believer in…whatever works. I think I’m fairly realistic about what modern medicine can, and cannot cure. If you’ve got a perforated appendix, then medicine is on it. But I also know many, many people with conditions like chronic back pain for whom modern medicine has been worse than useless (and indeed harmful), whose lives have been improved beyond measure by therapies for which there is no good, scientifically valid evidence base.  I’m not saying science is the only way. What I am saying is that if you want valid scientifically-based advice, then the guidance above is a good way to start in the highly variable world of microbiomes.

I don’t have a problem in people paying for hope, or quick fixes, where there are none from scientific medicine. I know these things are often sold, or talked about, by well-meaning people who want to help. Let’s face it, as I said, Scientists often get it wrong too, wanting to believe beyond what there is evidence for. But if people ask me for my opinion, it’s  that I don’t agree with a lot of the probiotic advertising currently going on – treatments that are guess, sold as a guarantee. Doubt, it seems,  doesn’t sell as well as magic.

So in the end, I guess  it’s make your own mind up time. Cautious certainty, or wild speculation? For me, even the cautious approach in microbiomes throws up incredible, wonderful things, in terms of the science, and revelations about how the body (and biology, and life) works. However (apart from the C.diff. story) I think we’re not quite at incredible, wondrous effects on the health of our patients. We’re at small, incremental increases, building the foundations for future leaps and bounds.

Note #3

Yes, I know chimpanzees don’t come from the Amazon, they come from the Congo and other African forested areas. Perhaps I should substitute Chimp for Marmoset, or Howler Monkey, or other Amazonian monkey. I did in the tundra image. I guess I’ve got used to the image of slightly confused and rather cold, grumpy chimps in Siberia to explain how I think about probiotics. After all, these bacteria are used to nice, happy bioreactors ideally set up for their life,  and end up somewhere very much less welcoming…

Images: Either attributed, or Pixabay, free for commercial/noncommercial use without attribution. Thanks Pixabay.

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Comments: Please let me know if there’s anything you think is inaccurate about this. I’m always interested in changing my views, and correcting my errors,  if it’s backed up by decent evidence.  However this is a blog aimed a promoting good quality science dialogue, and I won’t be publishing any comments which seek to promote products or services. If there’s a probiotic which someone knows DOES stand up to the level of scientific scrutiny required for a national body to recommend it’s use, do let me know. For the moment, that’s the point at which I’d change what I’d say, rather than promising evidence from limited studies.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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