Dec 18 2008

A New Analysis of Probiotics

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Comments: 12

A few months ago I blogged about so-called “good” bacteria. We are colonized by friendly bacteria that do not cause infections or harm, and in fact serve vital functions.

One of the specific topics I covered was probiotics – use of friendly bacteria species to improve the bacteria in our guts to help stave off infection or otherwise promote GI (gastrointestinal) health. Based on the evidence at the time I was luke warm on probiotics – the concept is sound, but the evidence for specific benefits is preliminary.

A new study, actually a meta-analysis and review of existing studies, published in the American Family Physician, has altered my assessment to be more positive.

Kligler and Cohrssen reviewed dozens of studies, and also prior reviews, such as Cochrane reviews, which are the standard for evidence-based medicine. They conclude:

Probiotics are microorganisms with potential health benefits. They may be used to prevent and treat antibiotic-associated diarrhea and acute infectious diarrhea. They may also be effective in relieving symptoms of irritable bowel syndrome, and in treating atopic dermatitis in children.

In thinking about any medical treatment it is important to note that specific treatments need to be assessed as to their safety and effectiveness in treating specific conditions. It is important to avoid oversimplifications, such as “probiotics work” – work for what, and in what dose?

Unfortunately, there is a natural tendency to oversimplify – it is one way to have a sense of control over our complex and often overwhelming world. Simplification, in fact, is necessary. We need to approximate reality with rules and characterizations that are mostly true most of the time. Oversimplification, however, implies that this process is taken to the extreme of being wrong. This is dangerous, or at least wasteful, when it comes to medicine.

With regard to probiotics, what this review supports is that certain doses of specific species of bacteria can help reduce the risk of developing diarrhea and the severity of diarrhea if it does develop. The concept is that friendly bacteria form a carpet lining all our mucous membranes. This carpet of bacteria keeps out any invading infectious bacteria, or at least limits its ability to multiply. When bacterial numbers ar reduced by antibiotics, this opens the door for infections from either viruses or resistant bacteria.

Taking some probiotic during antibiotic use reduces the risk of infectious diarrhea. It seems that these probiotic bacteria can help replace the killed good bacteria and keep our infections. There is even a dose response effect – 10 billion colony forming units of bacteria are better than 5 billion colony forming units.

However, the probiotics must be taking within 3 days of starting the antibiotic and the benefits are short lived. This is because the bacteria in probiotic products (like yogurt) do not seem to set up shop – they don’t form permanent self-sustaining colonies in the gut.  So they only help if you are actively taking them in large amounts while you need them.

Another limitation of probiotics is that they contain only one or a few species of bacteria. Meanwhile, our guts contain hundreds of species forming a real ecosystem. Adding a couple of species does not have a significant benefit to the ecosytem, which will have to recover its full diversity on its own over time.

So probiotics are not a cure, but they can be an effective band-aid. They can help crowd out infectious organisms during antibiotic use. They also appear to be relatively safe, so there is little downside to taking them except for the expense.

There is also evidence, although of less quality according to this review, to support the use of probiotics to relieve the symptoms of irritable bowel syndrome and atopic dermatitis. The evidence for these indications is more preliminary.

Here comes the risk of oversimplification – there is already an industry of probiotic products based upon the claim that routine use of probiotics has health benefits. There is no evidence for this, however. Evidence for a short-lived benefit during antibiotic use cannot be used to support the routine use of probiotics in the healthy.

A Google search on “probiotics” brings up many legitimate health advice sites that give a reasonable review of the evidence. It also brings up the websites of companies selling probiotics – and there is a clear disconnect between the evidence-based information at, say, WebMD, and the marketing hype promoting probiotic products (no surprise there).

Getrightprobiotics, for example, claims:

Patented Bio-tract technology promotes a healthy digestive tract. Reduce lactose intolerance, diarrhea, constipation, IBS, IBD, and more.

The first claim is simply a “structure-function” claim – promoting a healthy digestive tract. There is no credible evidence or scientific consensus for this claim, but in the US companies are free to make such claims without any oversight or evidence.  Evidence for lactose intolerance and IBS are preliminary and lack consensus. For diarrhea, as I discussed above, the benefits are short-lived and only during antibiotic use.

But companies do not want people to use their probiotic products only for occasional short periods of time, they want them to use them every day. So that is the claim they make.

Perhaps the bigger problem, though, is that probiotics are regulated like supplements (which means hardly at all). Therefore it is very difficult to know how to apply the evidence to any particular product. Some information should be readily available on labels – what bacterial species are claimed to be present and it what amounts. The evidence suggests that at least 5 billion bacteria, or colony forming units (meaning live bacteria able to reproduce) are required for benefits, and 10 billion are better. But some product boast 4 billion bacteria – which sounds like a lot, even though it is a low dose.

There is also no standard quality control. Are the bacteria said to be present really in the product? How pure is the culture? Are they alive in the numbers claimed?

For pharmaceuticals when a patent expires and companies are able to produce generic alternatives, they have to do studies to demonstrate equivalence to the approved brand name drug – even though they are still producing the same active ingredient, the same molecule. There is no such requirement for probiotics.

Conclusion

Overall, I am actually supportive of the concept of probiotics. The theory is sound, it is likely a low risk intervention, and I think there is tremendous potential for the future. This latest review pushes me over the threshold of concluding that certain probiotics in sufficient doses are safe and effective for temporary prevention and treatment of antibiotic-associated diarrhea. There are other plausible indications with some positive evidence, but more study is needed.

However, the application of this scientific data is frustrated by an unregulated market for probiotics. The marketing claims being made go well beyond the evidence, emphasize continuous as opposed to as-needed use, and there is no standardization. Consumers are therefore not being well served. There is some independent analysis available, but this only looks at the content and quality of products, not health claims.

What we need is not only better quality control for products, but effective regulation of the health claims made for these products. And this regulation should be based upon clinical studies showing efficacy of specific products for specific indications or benefits.

Otherwise, use of probiotics by consumers is a crap-shoot.

12 responses so far

12 Responses to “A New Analysis of Probiotics”

  1. NeuroTrumpeteron 18 Dec 2008 at 12:54 pm

    I’m going to guess that the “UFOs/Aliens” tag is a mistake…

    Although I suppose bacteria could be considered aliens in the sense that they’re not us, even though they out-number our cells by 10 to 1

  2. sonicon 18 Dec 2008 at 6:10 pm

    This is great stuff.
    It would be nice if we knew all the types of bacteria that help us. This would lead to better products.
    I think there is a fallacy at work here- “If you take this once it is helpful. You should take it everyday then.”
    “If one beer is good, then 12 should be better.”
    I’ll call this the ‘drinker’s fallacy’ unless you have a better name.

  3. HHCon 18 Dec 2008 at 6:52 pm

    L. acidophilus cultures in yogurt works well with the use of antibiotics. As a consumer and occasional clinical food testor, I can say truthfully that the Liifeway Kefir products work. Some more highly advertised yogurt products create imbalances. Yogurts with natural sugars are best.

  4. Gary Goldwateron 18 Dec 2008 at 8:17 pm

    This is interesting.

    My understanding is that when a baby is born, s/he has little or no flora-culture [if that’s a word] in the gut. Yet, the baby gets some level of immunity from the lactating mother. In the meantime, the baby ingests enough cultures to begin a healthy gut culture on his/her own.

    Would this pro-biotic research suggest experiments with probiotics in babies who can not get breast milk…or perhaps in all babies as a propholactic against disease until a naturally metabolized & healthy culture takes over?

    I think a lot of the newbie deaths in the 3rd world are from complications of gut afflictions…like diarrhea.

    But, here’s my question. Why not inoculate with known mixtures of gut bacteria that are known to inhabit the healthy human gut? Shouldn’t the environment select-out a bacterium that doesn’t belong the same as it would for the species used to make yoghurt? In the meantime, the gut can metabolize the actual bacteria that can be useful to digestion, nutrition, and other health functions?

    Does anyone know why we are experimenting with a bacterium that will be selected-out?

    I understand the experiment as a proof-of-concept for using a bacterium that will be selected-out while being a “place-occupier” for the bacteria that will later be selected. But isn’t this an extremely weak approach when compared to drug supplied assaults designed to limit the body’s cultivation of infectious bacteria?

    Another question I have is: as different harmful bacteria are selected to navigate through the pro-biotics and thrive on them, will we be better off, worse off, or neither in the end?

  5. MCRISLIPon 18 Dec 2008 at 10:04 pm

    at the national ID meetings there have been posters that demonstate that what is on the label of the probiotic is not what is grown when cultured and often the pills are sterile.

    At most of my hospitals patients started on antibiotics get a brand of natural yogurt that is full of the same bacteria in the pills.

    as a food I would bet it is produced with better standards.

    the closer the yogurt is to stool the better.

    as to goldwaters question.

    my e coli may not be your e coli and so there is more potential for disease if you get a new strain of bacteria. they have tried attenuated strains of e coli to prevent urinary tract infections in quads with success, but if you are going to take stool bugs, you probably want those from your children > spouse > random donor. the flora of the gut, the strains of common organisms, may in part be genetically determined.

  6. daedalus2uon 18 Dec 2008 at 11:16 pm

    Gary, when a normal infant is in utero, their gut is completely sterile, as is their skin. A normal birth does expose them to the normal vaginal flora.

    The problem with trying to supply a known mixed consortium of beneficial bacteria is that the normal flora of the gut is extremely complicated; hundreds of species and many of them are not culturable. Virtually all of these bacteria can be opportunistic pathogens. They may usually be benign, or even beneficial, but in some patients may cause harm. The bacteria in yogurt have been known to cause heart infections, and also liver abscesses. If you give a patient a mix of 100 different bacteria and they get sick, who is liable? How do you test a mix of 100 different bacteria? One at a time?

    There are some programs to look at the human microbiome using culture independent methods (usually just sequencing everything then putting the bits together).

    Essentially the only bacteria that are being looked for are heterotrophic bacteria. As far as I know, I am the only person doing any research at all on autotrophic bacteria as commensal organisms. All the culture techniques that have been used to date would not find the bacteria I am working with and which I have found can survive long term on human skin and become the dominant flora. None of the people I have talked with looking at human commensals have been the slightest bit interested in working with me.

  7. superdaveon 19 Dec 2008 at 2:17 am

    kefir strawberry yogurt smoothie tastes awesome. That’s all I need to know.

  8. Gary Goldwateron 19 Dec 2008 at 2:23 am

    Thanks Dr. C. Daedalus, & Dr. N. This is a great place for a guy to get an education. Thanks for answering questions [previously and now]. I sincerely appreciate your thoughtfulness. It gives me a lot to think about.

    Daedalus, wouldn’t someone from a deodorant company fund study on commensuals? Just a wild guess. But isn’t the result of the body’s culturing of commensual bacteria the target of their multi-billion dollar industry? Or perhaps I learned that wrong.

  9. daedalus2uon 19 Dec 2008 at 9:58 am

    Virtually all companies don’t fund much external basic research unless it is directly involved in their products, and they have a proprietary interest in it.

    The research on commensals is basis research funded by the government. I am very excited by it, because I think it will confirm the presence of the bacteria I am working with; provided the correct human populations are looked at. Those would be people living in rural undeveloped regions where they do not have access to abundant clean water to use for bathing. As a consequence they don’t bathe and so have a “natural” commensal surface biofilm; the biofilm humans evolved to have on their skin.

    There is a large gradient in many diseases between the rural undeveloped world and the developed world. Heart disease, obesity, hypertension, diabetes, allergies, asthma, kidney failure are virtually unknown in the rural undeveloped world. The hygiene hypothesis has been suggested to explain this gradient as being due to exposure to some environmental factor, some disease, parasite or even dirt. So far no such factor has been found. I am pretty sure that factor is the ammonia oxidizing bacteria I am working with. The only reason it hasn’t been found is because the proper culturing techniques were not used.

  10. frodeon 23 Dec 2008 at 10:30 pm

    Daedalus, I’ve heard that the reason there’s less “Western” diseases (heart disease, obesity, etc) in undeveloped areas is simply due to the diet of the people.

    The typical diet there is low in the rich foods common in the west, and higher in the basic carbohydrates, like rice or potatoes.

    Once people from these areas begin eating the fat and cholesterol rich Western diet, they develop these diseases to the same rate as the “native” Westerners.

    I’m neither a professional scientist, nutritionist or medical practitioner, but in my reading about this, there appears to be quite a bit of supporting research in the medical literature.

    Just thought I’d mention it, as it seems that hadn’t occurred to you. 🙂

  11. KBot84on 06 Jan 2009 at 6:20 pm

    I found an overview of probiotic studies and research at http://www.truthaboutprobiotics.com. It is troublesome that they are marketed as supplements so there’s no regulation. People could literally sell sawdust in a bottle and call it a probiotic.

  12. Skeptic Smash-Talkon 24 Oct 2016 at 8:12 am

    Hi Steve, I know this is quite old now, but is this still your current opinion, I’m doing a story on this and collecting research and opinions and yours are normally quite valid 🙂

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