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I’ve been prescribed an antibiotic. Should I take a probiotic?

We are not one organism, we are many organisms. And when we disturb the relationship with our symbiotic partners, we can suffer unpleasant and sometimes life-threatening consequences. One of the most fascinating areas of medical research is the study of how our bodies interact with the the various organisms that we carry around, on us and in us. A focus is the gastrointestinal tract, particularly how the composition and function of those organisms contribute to what we think of as “normal” function, and how they can affect our risk for obesity and disease. My favorite analogy is from SBM’s own Mark Crislip who likened it to a “metaphorical rainforest” giving a vivid mental image of the of the number of species (thousands) in our guts, and the complexity of that ecology. If the gastrointestinal tract is a rainforest, then antibiotics are the metaphorical clear cutters, wiping out some of the normal bacteria, and creating the conditions where unwanted bacteria can grow.

Antibiotics are among the most useful (if not the most useful) classes of drugs in widespread use today. They’re also among the most widely prescribed, and both antibiotic overuse and their addition to animal feed present real dangers to their ongoing effectiveness. Their popularity stems in part from their effectiveness, but also from the perception that they are safe. And, in general, a course of most antibiotics is usually well tolerated. Among the side effects, diarrhea is common (with an incidence of 5% to 39%). It’s due in part to the antibiotic killing off  our normal “good” bacteria, which can significantly change the most prevalent species. In some cases, “bad” bacteria can surge as a result. Clostridium difficile infection is pretty much the worst gastrointestinal consequence of antibiotic therapy. It isn’t just a cause of antibiotic-induced diarrhea, “C. diff” infections are virulent and vicious, spreading easily, especially among hospitalized patients, causing widespread misery and even killing.Probiotics are some of the more interesting of the “complementary and alternative” products out there, because they’re among the more plausible. Probiotics are bacteria and yeast that are administered to replace the bacteria killed by other means, with the goal of reducing the risk of diarrhea and the chance of serious infections from pathogens like C. diff. But plausible doesn’t mean valid – remember the idea that antioxidant vitamins would be beneficial? Or preventing arrhythmias would reduce mortality? Science has repeatedly shown the hazards of making assumptions of benefit in the absence of clear evidence. Given the complexity of the body’s ecosystem, it’s reasonable to be skeptical of the concept of probiotics. Again, Crislip’s analogy of probiotics to be akin to “planting corn in a rainforest” is one that I use a lot. Plausibility is one thing, a demonstrable effect is another. For that, we need to see the evidence.

Proponents of probiotics liken their effect to some sort of bacterial and mycological panacea, providing benefits that range from nonspecific (“wellness”) to promising (prevention of respiratory tract infections) to the somewhat more established uses, like the prevention of antibiotic-associated diarrhea (AAD). To keep the topic focused, I’ll consider a typical use: starting a probiotic when you start an antibiotic, with the goal of preventing diarrhea. For the sake of simplicity and to make this relevant, let’s assume you’re not hospitalized, nor do you have any underlying gastrointestinal disease, like Crohn’s.  Let’s assume you’ve been prescribed oral antibiotics for an infection that’s usually treated at home, such as a urinary tract infections, a skin or soft tissue infections, or a lung or other respiratory tract infection. Is the use of a probiotic a good investment for you?

The evidence

Reviewing trials with probiotics is complicated by an array of studies, endpoints, prior antibiotics, patient populations, and the quality of the studies. The result is a number of endpoints that a few authors have attempted to systematically evaluate with meta-analyses. Admittedly a meta-analysis is not the ideal tool under these circumstances, but it does give a sense of the overall evidence base.

Hempel’s meta-analysis, published in 2012, is the most recent review. It looked at 82 studies and combined the results of 63 RCTs, giving a sample set of almost 12,000 patients taking antibiotics, comparing probiotics to placebo or no therapy. Probiotic species included Lactobacillus, Bifidobacterium, and the yeast Saccharomyces. The overall findings were impressive. Those taking probiotics had a 42 percent lower risk antibiotic-associated diarrhea. Based on this analysis, 13 people who would otherwise experience AAD need to take probiotics to prevent one. So it’s not a panacea, but as interventions go, this is a good number needed to treat (NNT). Subgroup analysis, including an analysis of the highest-quality trials, didn’t change the effect size significantly – the effect was also consistent in both adults in kids, though it was non-significant in seniors. Of the studies that collected adverse event information (23) none were noted, which is reassuring but makes me skeptical that this information was collected accurately. It should be noted that most trials were sponsored by manufacturers, introducing an additional potential bias in the individual studies that would be reflected in these results.

Hempel’s review is not the first meta-analysis of probiotics for AAD. Its conclusions are broadly in line with Sazawal, D’Souza, Van Niel, Szajewska and McFarland. There is also the 2011 Cochrane review by Johnston that looked specifically at probiotics to prevent AAD in children, selecting 16 trials of over 3400 patients. Despite the numerous data quality issues, it concluded that there is likely a beneficial effect from probiotics, but the overall quality of the evidence for the primary endpoint (incidence of diarrhea) was low. It calculated an NNT of 7, even more impressive than Hempel’s review. Again, no serious side effects were associated with probiotics. The review called for more studies to better establish the appropriate probiotic species, dose, duration and side effect profile.

The other recent meta-analysis is from Videlock in 2012, pulling together 34 studies with over 4000 patients. Species included Lactobacillus, Enterococcus, Streptococcus, and the yeast Saccharomyces. It estimated the overall relative risk of diarrhea when taking probiotics to be 0.53 (95% CI 0.44-0.63), suggesting an NNT of 8 (95% CI 7-11). Both of these estimates are difficult to interpret given the diversity of trials and endpoints in the included studies. Problems in the analysis included the suggestion that the results are positively biased because of negative trial bias. Side effects were not notable. Overall, positive findings but the limitations in the data suggest that we need to accept these estimates of efficacy with some caution.

When probiotics are given specifically to prevent C. diff infections (versus just diarrhea) the Hempel analysis suggests that there is expected to be a net benefit. A 2013 Cochrane review by Goldenberg suggets that probiotics can reduce the risk of infection by 64%. There are also reviews by Ritchie and Bradley that suggest a net benefit. Again, the merits really depend on the likelihood of a C. diff infection, which is relatively unlikely in the otherwise healthy, unhospitalized person.

Guidelines, position statements, and regulators

The Australian not-for-profit NPS Medwise says the following about probiotics and antibiotics:

There is not enough evidence to determine the following about probiotics:

  • The minimum dose that is effective for preventing antibiotic-associated diarrhoea
  • How well they work for different age groups
  • Whether they prevent diarrhoea caused by Clostridium difficile (which can lead to more serious complications)
  • How different probiotics compare in effectiveness and safety
  • The best length of time to take them for
  • Whether the effect of a probiotic differs depending on the type of antibiotic taken or for how long the antibiotic is taken.

The Canadian Pediatric Society’s guideline has a nice compilation of the data, and suggests the following in its 2012 guideline:

 Keeping in mind that the effect of probiotics is both strain- and disease-specific, physicians should consider recommending probiotics to prevent antibiotic-associated diarrhea.

The European Food Safety Authority has reviewed many probiotic products for treatment claims made by manufacturers. A review of any of their evaluations illustrates the problems with the individual trials that make up the probiotic evidence base. Reviews point out methodological weaknesses that preclude conclusions about cause and effect. They also criticize manufacturers for not demonstrating that the product they are selling is identical to the product studied in their clinical trials, which is a necessity if manufacturers want to infer efficacy from these studies.

Risks

Given the diversity of products studied, patient populations and the underlying quality of the data, it’s difficult to make a single statement about the potential harms. However, it is reassuring that there is little evidence in the literature to suggest that probiotics are harmful. The exception seems to be those with weakened or compromised immune systems, where serious cases of infection have been observed. And once you have antibiotic-associated diarrhea, the case that can be made for probiotics is less clear.

The weak regulatory structure for probiotics makes quality control more questionable that you would find for prescription drugs. The degree to which consumers can expect a reliable product is not clear. Analyses have shown that labels may be inaccurate with respect to types and quantities of species included. Variations from the label have been observed in other studies, too. This may introduce the risk of an infection from an undesirable species.

Discussion

On balance, probiotics have a good safety record and clinical trials of moderate quality suggest that they may reduce the risks of antibiotic-induced diarrhea. Whether or not probiotics should be recommended routinely is still a matter of debate.  There is still a lack of information about the most effective species, the optimal dose, and the timing of product. While there remains contradictory data, there seems to be enough evidence to suggest that there is a net beneficial effect. No standard doses exist, nor does the optimal duration of treatment, though most studies evaluated supplementation during the duration of the antibiotic therapy.

I haven’t covered specific brands of probiotics at all in this post. (Some are discussed in Dr. Crislip’s post.) Frustratingly there is a lack of good data to help distinguish which brands and species of probiotics are demonstrably and reliably effective, or if one is superior to another. There is no head-to-head data to compare formulations. There are many claims that the multi-species formulas are superior, but this hasn’t been clearly shown to be the case.  Yogurt is often suggested as a source of healthy bacteria. However, the probiotics used to ferment milk (L. bulgaricus and S. thermophilus) are not believed to survive the trip through the gastrointestinal tract. Acid-resistant probiotics (e.g., L. acidophilus) added to yogurt can make the product an effective probiotic source. Depending on where you live you may also see yogurt-like fermented dairy products such as DanActive and Bio-K Plus in your grocery store, created to provide a source of probiotics.

Costs vary dramatically. A Canadian review noted the 14 day costs of probiotics with the best evidence for C. diff prevention ranges from $13 (for Bio-K+) to $112 (for VSL#3).

Importantly and probably most frustratingly, the lowered safety and quality bar in place for “supplements” regulated (I use that term loosely) under the DSHEA makes it difficult to identify a preferred product. It’s not clear that what’s on the label is actually on the bottle, especially when it comes to live bacterial cultures. Even industry insiders note the problems with the manufacturing quality of these products.

Conclusion

There’s reasonably good evidence that probiotics, when taken with antibiotics, will reduce the risk of antibiotic-associated diarrhea. There is still much to be learned about how these products can be used most effectively, which means it’s unlikely we will see routine use recommended for some time. However, the reassuring lack of side effects, and potential to reduce potentially serious complications of antibiotic treatment, suggests that probiotics may become a valuable addition to antibiotic therapy.

Posted in: Herbs & Supplements

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38 thoughts on “I’ve been prescribed an antibiotic. Should I take a probiotic?

  1. leeann says:

    So how does one know what species of probiotics to take? Are there any “broad spectrum Pro-Biotics”?

    1. barkshardly says:

      My understanding after the reading I have done is that there is insufficient evidence to answer your first question. In answer to your second question, yes, there are “broad spectrum” probiotics, and that is what I will choose to take before, during, and after my course of antibiotics to treat an intestinal parasite. For travelling I bought Probaclac Travellers probiotic with 9 different strains. I was just reading about Bio K, which apparently only has two strains. I have no idea what to choose, but I will probably go for another option that has more strains.

  2. anthro49 says:

    Is a bit of temporary diarrhea really the worst thing in the world? I have only had if from a particular antibiotic once or twice and somehow survived–without suffering dehydration even.

    If a real problem exists, then we need to do the work to find the appropriate and effective dose of probiotics and start manufacturing them the same as other drugs so they can be used appropriately.

    I really do appreciate your looking at this issue as it’s one of the biggest cure-alls out there for any sort of stomach distress. I cannot tell you how many people have told me to use probiotics at the slightest sign of a stomach ache, let alone diarrhea.

    1. BadWolf says:

      The thing is, diarrhea is really horrible. As someone who is on 1,350mg of Clindamycin per day for cellulitis, it really interrupts my class schedule (both making me late for class and missing things in class), my ability to work out, etc. — I am always on the lookout for bathrooms. Also, as a woman, I’m worried about getting a yeast infection from my antibiotics. If I can do anything to keep those things at bay, I will–including buying overpriced Greek yogurt and Kafir drinks because they have the “Live and Active Cultures” seal.

      I would love to be able to just take a pill along with my antibiotics. It’s true that there needs to be more research, but probiotics are in fashion right now and that makes people crazy about Activia, and it also means that stubborn people like you will say “Everyone’s telling me to eat yogurt, and I don’t want to do what everyone says! Give me a pill!”

    2. BadWolf says:

      The thing is, diarrhea is really horrible. As someone who is on 1,350mg of Clindamycin per day for cellulitis, it really interrupts my class schedule (both making me late for class and missing things in class), my ability to work out, etc. — I am always on the lookout for bathrooms. Also, as a woman, I’m worried about getting a yeast infection from my antibiotics. If I can do anything to keep those things at bay, I will–including buying overpriced Greek yogurt and Kafir drinks because they have the “Live and Active Cultures” seal.

      I would love to be able to just take a pill along with my antibiotics. It’s true that there needs to be more research, but probiotics are in fashion right now and that makes people crazy about Activia, and it also means that stubborn people like you will say “Everyone’s telling me to eat yogurt, and I don’t want to do what everyone says! Give me a pill!”

  3. c0nc0rdance says:

    I had the pleasure to work with a researcher at the local veterinary school who was collaborating with dog food companies to study dietary probiotics in dogs with digestive problems. The data is unpublished, and likely will remain so, but I recall that when you put 10^10 Lactobacilli into the front end of the dog, you pretty much get 10^10 Lactobacilli out the back end of the dog (hooray for fecal PCR!). Experimentally, there was no way to determine what factors determined “engraftment” of the probiotic species, so almost all of the Lactobacillus were just on the world’s worst dog-themed roller coaster ride to the grass.

    Probiotics are a pretty crude tool at the moment and the way we use them doesn’t seem much different than the ages-old scientific practice of “poke it with a stick” or “add more and see what happens”. I suspect that the future of microbial ecology will be very bright, but there’s a need to understand a little better the basic science of how a microbial community interacts with the host and each other.

    It’s worth celebrating that the research tools needed to study microbial communities effectively (next-generation sequencing) have only been around for <10 years, and yet the data we've already produced have been revolutionary.

    1. windriven says:

      Correct me if I’m wrong but I believe that under decent conditions lactobacilli can reproduce every hour or two. The input equals output idea you offered presumes either a very brief transit time or an absence of reproduction in transit.

      1. Andrey Pavlov says:

        Or, more likely, death through the GI tract with subsequent re population. Also likely is that under the stress of being churned up in the stomach the bugs don’t reproduce for a while. It is common for bacteria to get “stunned” and stop reproducing under environmental stress. Also, measuring techniques have inherent error and are rounded to essentially an order of magnitude. So really, we can’t conclude no change, nor same initial population (though tagged studies would be cool and shed light on this), but that output is roughly the same as input.

  4. Alia says:

    Well, over here it’s standard to recommend probiotics with antibiotic treatment and it’s been like that for many years. I remember that when I was a kid and had to take antibiotics for ear infections, I would also get the only brand of probiotic available then (Lactobacillus rhamnosus).
    @anthro49 – “just a bit of temporary diarrhea” can make your life utterly miserable, which I learnt all too well when I was on augumentin following invasive dental surgery. And if there’s even a small chance that by investing an equivalent of $15 into a probiotic I can avoid it, well, I’m in.
    Fortunately, I haven’t taken any antibiotics for five or six years now and I hope it will stay that way. I’m not goint to take probiotics in any other case.

  5. WilliamLawrenceUtridge says:

    First, huge fan, I love your youtube videos. Yours is the only channel I have a subscription for. Gush gush gush!!!

    Second, is there any reason to expect dog guts to react to/contain the same bacteria as people guts? As predators, don’t they have a totally different digestive tract (high-acid, short and fast-moving) compared to us omnivores? Do wild dogs and wolves have Lactobacilli in their digestive tract in the first place, or totally separate species?

    1. Calli Arcale says:

      They’re different, but maybe not quite as different as you think. Dogs are probably closer to us than cats are; they’re at least partially omnivorous and unlike cats, can actually turn into lardbuckets on a vegan diet. Cats don’t. Unless they’re rigorously supplemented, they go blind, and then they die, which is one of the reasons I hate PETA — they promote feeding only veggies to your kitties. I suspect this only works if the cat is allowed to roam, supplementing its diet with the local wildlife.

      1. Stephen H says:

        Thanks for the heads-up on PETA stupidity. I hadn’t heard that before, but a quick check of the interwebs showed them encouraging people to feed a carnivorous animal a herbivorous diet – morons.

        My wife and I have switched to dogs, but have previously been cat owners. There are some big, obvious differences between the animals and their dietary needs. Anyone suggesting that cats should be persuaded of “the benefits of the vegan diet” should be put down for animal cruelty and extreme stupidity.

    2. Andrey Pavlov says:

      Agreed. I’ve watched every one of his videos. They are awesome and so is he (even when we disagree a bit).

  6. WilliamLawrenceUtridge says:

    1) My above reply is aimed at c0nc0rdance

    2) A question possibly for Dr. Crislip – does taking probiotics reduce the effectiveness of the antibiotics, do they act like cannon fodder for the pills?

  7. jsm1031 says:

    And is there evidence that a probiotic in pill form is any better than a good diet? The food we serve in hospital tends not to have many fresh fruits, vegetables and is typically also low on beans, pickles, kraut, etc. But those could certainly be encouraged on a home diet, along with the over sold yogurt.

    1. dave858 says:

      That’s an idea I hadn’t considered – is there evidence for non-probiotic dietary changes to alleviate the negative effects of antibiotics?

  8. Young CC Prof says:

    Antibiotic-associated diarrhea CAN be a big problem, even without C. diff. My father had to have IV vancomycin when he developed a fever after his hip replacement, and it screwed up his digestion unbelievably. He lost 12 pounds in a matter of days, and it took opiates to get him absorbing food again.

    But yeah, probiotics are overhyped. It’s clear there’s a connection between gut microbes and health, and replacing intestinal flora after antibiotics is probably a good idea, we just don’t understand anywhere near enough about it.

    1. windriven says:

      “replacing intestinal flora after antibiotics is probably a good idea, we just don’t understand anywhere near enough about it.”

      I understand this much: if my choice is between probiotics and a fecal transplant, I’ll start with the probiotics. Probiotics may have an uncertain upside but there is almost zero downside and a pretty much flat-lined yuck factor.

  9. angorarabbit says:

    Oh, I’d definitely go with the transplant – at least it would be closer to what ought to be present. There’s not a lot of relationship between the commercial products and what’s actually resident.

    We do this a lot in our rabbit rescue because they are hindgut fermenters. They often get cecal dysbiosis in response to stressors; the gut shuts down and Clostridium grows, killing the bunny in a day or two. Commercial probiotics are, well, I was going to say a load of crap, but no, the crap is better. We capture the cecal microbes that a healthy rabbit passes and give it to the animal with dysbiosis. Works pretty well to repopulate and suppress the Clostridium and other nasties.

    Apparently our own microbiome must repopulate pretty normally after a colorectal inspection, but I still wonder about that.

    1. Thor says:

      I’ve been wondering that as well. My father had a colonoscopy at age 79. Up to that point, he never had a digestive complaint/problem in his life, except for the occasional minor event almost everyone gets at one time or the other. His bowel function remained altered from that point on till his death at 84. It wasn’t serious, but different than before and, according to him, less efficient and often uncomfortable (not much diarrhea, though). Granted, it is only a ‘trial’ of one, and there could be other factors involved. We tried various probiotics but none resolved the issue. When I had a colonoscopy, it took about a week for things to normalize. I ingested no probiotics.
      Transplants would logically be superior to oral, but I think most of us would hesitate like windriven due to the thought of it. This certainly is an exciting area for discovery.

  10. Anna says:

    When my cat experienced diarrhea while on antibiotics, my vet suggested feeding her yogurt. That did make me raise my eyebrow, but I tried it. And who even knows if it helped or not — it kind of seemed to, but I was only testing it on one cat so I can’t really say.

  11. Reade Bricker says:

    Probiotics may be a sham today, but studies regarding bacterial populations, density, diversity, and relationship with the host should provide a better basis for formulations in the future.
    Identifying and culturing the right bacterial populations may be key to treating various bowel syndromes as well as other syndromes like acne and some kinds of obesity.
    More research is needed to link the populations to the syndromes, and to identify factors which regulate the populations. Need to separate cause from effect.

  12. Denise D. says:

    When I was in the PharmD program, as part of the Infectious Diseases module I developed and analyzed this clinical question: “In elderly hospital patients who have suffered from recurrent episodes of Clostridium difficile-related colitis, is the administration of the probiotic Saccharomyces boulardii a safe and effective means of C. difficile colitis prophylaxis?”

    Short answer: no. At that time (2009), I didn’t find any trials of probiotics for C. diff prophylaxis specifically, though there were plenty addressing the prophylaxis of AB-associated diarrhea, some of which included patients with C. diff. I analyzed 2 papers more closely: Prevention of antibiotic-associated diarrhea by saccharomyces boulardii: a prospective study (Gastroenterology 1989; 96: 981-8), and Saccharomyces cerevisiae fungemia: an emerging infectious disease (Clin Infectious Dis 2005; 40: 1625-34). So benefits vs risks.

    In the 1st paper, there was a stat sig benefit to S. boulardii administration: 14 of 64 (21.8%) in the placebo group developed diarrhea, compared with 11 of 116 (9.5%) in the treatment group (p = 0.038). And the patients in the treatment group who developed diarrhea had it less severely. There was also a benefit found for patients testing positive for C. diff, but the sample size was too small to find a stat sig benefit: 48 patients positive for C. difficile; of those, 5 of 16 (31.3%) of the placebo group and 3 of 32 (9.4%) from the treatment group developed diarrhea (NS; p = 0.07). I suggested in my analysis that if S. boulardii was completely safe, it might be worthy of better-powered studies in the prevention C. diff colitis.

    The second paper considers the safety of S. boulardii. The first part of the paper describes the clinical course of three prospectively-identified ICU patients who developed S. cerevisiae fungemia subsequent to receiving treatment with S. boulardii for C. difficile colitis secondary to antibiotic use. All three patients were over 70 years old; all three died, one of bacterial sepsis, one of a stroke subsequent to finding a vegetation on a prosthetic heart valve. The third patient died “unexpectedly,” having received no antifungal treatment after results of cultures were inconsistent. The authors then searched the literature for other cases of Saccharomyces fungemia, using the search terms, “Saccharomyces,” “Cerevisiae,” and “Boulardii,” and found 57 other cases of fungemia. For the purpose of their analysis, the authors included only those cases where genus Saccharomyces was definitively isolated from the blood, and where there was sufficient clinical data to enable a comparison with other patients, including their three patients in the analysis. The authors then searched the literature for other cases of Saccharomyces fungemia, using the search terms, “Saccharomyces,” “Cerevisiae,” and “Boulardii,” and found 57 other cases of fungemia. The authors then searched the literature for other cases of Saccharomyces fungemia, using the search terms, “Saccharomyces,” “Cerevisiae,” and “Boulardii,” and found 57 other cases of fungemia. The clinical presentation consisted of isolated fungemia (82%); endocarditis or periaortic abscess (8.3%); disseminated disease (6.7%); liver abscess (1 patient), and esophageal ulcer (1 patient). Eighty percent received antifungal therapy, either fluconazole or amphotericin B, or both. The mortality rate was 28% and the only factor associated with mortality was advanced age: the mean age of those who died was 60, compared with 36 years old for the survivors.

    My conclusion was that S. boulardii was not safe and effective for C. diff prophylaxis. There were cases of fungemia that occured in patients who were not receiving the probiotic, but shared the same room with patients who did. Yeasts can persist on surfaces for up to two hours and can be found on the hands of health care workers even after thorough hand-washing. And the risk of fungemia is not restricted to patients with clinical syndromes suggesting immune suppression; some were (AIDS, leukemia), many were not (trauma, cardiac surgery, myocardial infarction).

    True, the focus of my clinical question was not the same as your thesis. But I suggest that the risks of probiotics are under-recognized and perhaps under-reported, and we need to use caution when recommending these in the elderly and immunosuppressed.

  13. Denise D. says:

    TL;DR to my previous post: maybe there are unrecognized fungemias from probiotics. For instance, my father-in-law has Crohn’s disease, CAD and frequent pneumonias, and gets a course of ABs about half a dozen times a year. His wife and daughter buy him probiotics @ the health food store, his daughter urging him to take probiotics on a chronic basis. I think this sort of scenario is all too common.

  14. daedalus2u says:

    Is there some way to fix the comments? If I put more than 3 lines in the comment, the “post comment” button is gone. At two lines is is half invisible, at 3 it is gone.

    1. WilliamLawrenceUtridge says:

      I now compose using notepad or word. In Chrome the window expands as you type, but only to a certain limit.

      To get the post comment button to show up, hit tab once.

  15. daedalus2u says:

    One of the difficulties in approaching the issue of probiotics with an SBM approach is that the complexity is such that every application is essentially a unique anecdote. We know that the diversity of a normal gut is extremely high. What we don’t know is what part of that diversity is it that makes it “normal”, and how much of that “diversity” is a necessary but idiosyncratic response to the details of the specific genome, diet and immune system of the individual. Note the immune system is not specified by the genome, it is mostly “learned” by exposure to various bacteria, viruses, parasites, foods, vaccines and what not, so that even MZ twins do not have identical immune systems.

    The regulatory framework that probiotics are forced to be used in presents difficulties. Preventing or treating diarrhea is a “medical” claim, which requires the treatment be a “safe and effective drug”, which requires an investigational new drug application before it can legally be tested as a drug. The costs to do that are not insignificant. Most bacteria that are now used as probiotics are GRAS for use in food. GRAS as food does not mean “safe and effective” as a drug, or GRAS as a drug.

    One of the serious problems of antibiotic use is C. diff. That kills about 12,000 people per year. Fecal transplants can “cure” a C diff infection in a few days in ~90%+ of cases. Unfortunately, treating a C. diff infection is a “drug” claim, and so needs drug-like regulation. The FDA initially said that fecal transplants would require investigational new drug applications which made it impossibly expensive to do research on.

    It is likely that the use of common bacteria in fecal transplants won’t be patentable. So how are the sellers of such things supposed to pay for the research necessary to ensure that such treatments are safe and effective? Without data, you can’t do SBM. Without research you don’t have data. Without research funding you don’t have research. Government funding? Anti-science journalists and politicians will have a field day about spending government resources on the health effects of eating a literal “shit sandwich”.

    Autologous fecal transplants (your own feces from before you had antibiotics) would likely be pretty (if not completely) safe (provided you didn’t have parasites). That might not be effective because having a severe infection does “prime” the immune system to kill bacteria, and some commensals get killed and the immune system sensitized to them so they can no longer persist. That is probably a good idea for something like a colonoscopy. That would probably be a good thing to do during a check-up, take a fecal sample, assay what bacteria are in it, and save a sample for future need. I could imagine do-it-yourself kits. That would get around the FDA because nothing potentially pathogenic is being bought or sold, just the kit to save the specimens.

    It has been pointed out that most of the commercial probiotics are not actually bacteria that are normally resident in the gut. They might still help. When antibiotics kill off some of the resident commensal gut bacteria, they leave multiple open niches. Non-commensal bacteria and fungi fill those niches and pathogenic bacteria (like C. diff) produce toxins. If that niche is “filled” by a probiotic organism that consumes what ever the killed commensal bacteria were consuming, that (at least partially) eliminates the niche the pathogens are trying to fill.

    Common probiotic bacteria are the lactic acid bacteria that ferment sugars into lactic acid. If sugars are fermented into lactic acid, they are not available to be fermented into gas and toxins (and more bacteria that ferment sugars into gas and toxins).

    Thank you for the hit tab suggestion.

    1. Chris says:

      “Thank you for the hit tab suggestion”

      Please, don’t make me regret that!

    2. Chris says:

      Really, truly!?

      ;-)

  16. WilliamLawrenceUtridge says:

    Anti-science journalists and politicians will have a field day about spending government resources on the health effects of eating a literal “shit sandwich”.

    They might make the claim, but the public might be willing to eat that shit sandwich. You see a lot of popular media covering things like probiotics, the effects of antibiotics on gut bacteria and the like, so I wonder if this might be one case where absurd-sounding research is embraced by the public at large. It’s a relatively easy concept to convey, possibly sufficient for people to get around the ick factor.

    And if nothing else, you might be able to monetize a “fecal transplant kit”, which could support some funding. Geez, how do you get the good bacteria out, without getting all the nasty stuff at the same time? Centrifuges. I’m guessing the answer is centrifuges.

    As always D2U, very interesting.

    1. daedalus2u says:

      It is my understanding that everything in your own fecal matter is something you are already exposed to, and so there isn’t anything you are not already pretty much resistant to. Of course we all know that it is the dose that makes the poison (or cure). This is not to be confused with that other “perfect medicine”.

      http://www.amazon.com/Your-Own-Perfect-Medicine-Incredible/dp/0963209116

      Of course urine is pretty much sterile, so you wouldn’t get any probiotic benefit from it. I have been interested in urine therapy as part of my nitric oxide research. It turns out that where people do consume urine as part of their diet, there are no other sources of nitrate for them to consume. In Tibet, there are no green leafy vegetables for most of the year. Urine does have some nitrate in it, as the terminal metabolite of NO physiology. Urine stored under non-aseptic conditions would very likely also become colonized with ammonia oxidizing bacteria (the commensals I am working to commercialize) which would increase the NOx levels still more.

      I suspect that the proponents of urine therapy have lost track of the original physiology behind it, and by trying to keep it aseptic are defeating much of the benefit.

  17. Kieran Brooks says:

    Is there any evidence to suggest that pro biotics reduce the effectiveness of anti-biotics?

    1. daedalus2u says:

      There is probably no data on such things and likely data couldn’t be collected because it would be not ethical to follow subjects to treatment failure or to do treatment in such a way that treatment failure is possible.

      Some antibiotics do bind to specific molecules in bacteria (like the ribosome which does protein synthesis), so conceivably the presence of susceptible molecules (ribosomes that can bind the antibiotic) could conceivably reduce the concentration. It is likely that antibiotic resistance comes from the antibiotic not binding to what ever molecule the antibiotic inhibits. If the antibiotic doesn’t bind, then the solution concentration isn’t going to be changed.

      The major concentration of probiotics is going to be in the gut. If the infection being treated is somewhere other than the gut, the ability of bacteria in the gut to pull down the concentration is limited. IV antibiotics would not be expected to be pulled down by stuff in the gut (they are given IV because they are not absorbed from the gut). If they are not absorbed from the gut, they are likely to not enter the gut.

  18. WilliamLawrenceUtridge says:

    Humans are also probably seeing it wrong – bacteria are not a unitary class, there’s more diversity in that kingdom than there are in all the animals, from the malaria parasite to blue whales. The idea that the bacteria in your gut is the same as the bacteria causing a systemic infection is probably wrong – and there’s no real guarantee that the antibiotic would work on both anyway. As Dr. Crislip has mentioned in the past, antibiotics are specific to certain bacteria, there’s no such thing as “powerful” or “big gun” antibiotics.

    I hope someone shows up and proves me wrong on this, pointing out that C. difficile is in the same family as what they put in yogurt, I like learning new stuff.

  19. M.E. Morgan says:

    While I enjoyed the article, I feel that focusing on the use of probiotics for AAD is misleading. Probiotics do have a good track record with many other conditions, such as ulcerative colitis, vaginal infections and irritable bowel syndrome to mention a few. There is also a preparation that is even considered by the FDA as a medical food (VSL#3) and is recommended by many medical organisations.

    While it’s been mentioned that antibiotics are not likely to kill ingested probiotics because they don’t enter the gut, the fact that AAD does develop in some individuals suggests otherwise. This means that probiotics, given prophylactically or therapeutically, are likely to be affected/killed during an antibiotic onslaught. The fact that the meta-studies saw any kind of positive response is pretty amazing.

    Many probiotic species have been isolated from normal human feces. They are normally there in the gut. The problem is usually in the relative population size. People with inflammatory bowel disease, for example, have all species represented but the relative sizes of each population are much different than what would be found in a normal, healthy person.

    Having been involved in probiotic research studies in rodents, I can attest to the fact that they do have a significant effect at both the clinical and immunological level. Furthermore, there have been some absolutely stunning studies about bacteria published recently in PNAS, Nature and Science.

  20. Ben says:

    So I’ve been looking into probiotics a bunch recently and read this post on the bulletproof exec about why you want to avoid certain strains of probiotic that are histamine-producing: http://www.bulletproofexec.com/why-yogurt-and-probiotics-make-you-fat-and-foggy/
    After reading it I found these probiotics which have 2 of the histamine degrading strains (Bifidobacterium longum, Lactobacillus plantarum) and none of the histamine producing strains, so if that’s a concern of yours too, these should work well! They come in 30bn and 100bn versions for $35 and $63, respectively:
    Xymogen ProbioMax DF – 100 Billion CFU Probiotic – 30 vcaps
    XYMOGEN ProbioMax Daily DF 30 billion CFU probiotic 30 vege caps

  21. i currently am ending a 7 day script of clindamycin (900mg/day). i have an iron stomach and have had absolutely no problems with loose stool. i had gum surgery to repair gingeval recession. during my recovery i also used acidophilus probiotic (nature’s bounty) 1mg every dose of antibiotic (every 6 hours). the bottle says it contains “100 million organisms”. pretty impressive choice i reckon ay mate! should i attribute my lack of negative digestive side effects from the clindamycin to my use of the probioitic? not sure any type of evidence could conclusively suggest that. but even if physically there was no benefit from the probiotic, i felt as if it had a placebo mental effect on my recovery. so there you have it.

  22. why can’t i see my post?

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