[Note: I am not a doctor. Caution is the better part of valor here. Always be cautious when starting a new treatment, and never do it without the supervision of a doctor.]

 

Throughout this series, have alluded to my perspective on probiotic supplementation for IBD; I think it should be diverse. People with IBD should intake as many beneficial species as their body can handle.

Last week’s idea of a pathogenic community, a community of bacteria to which, because of its functional properties, our IBD-prone bodies react unfavorably, suggests that probiotic supplementation should encourage the building of an entire community of bacteria which are non-pathogenic to your body.

The question of how to best do that remains undecided in my mind. In my first post, I introduced Jini Patel Thompson’s approach using Natren probiotics; three or four (if you use B. infantis too) species, slowly introduced one at a time. This is a very good approach (the one I used) to beginning probiotic supplementation. It allows you to tell exactly how you react to each species, and allows you to tailor the doses accordingly (increase one, decrease another, etc.) However, it doesn’t meet my diversity criterion, and it didn’t work for me (more on this later).

Oh, what to do, what to do?

Evidence: Are Probiotic Mixtures more Effective than Single Strains?

The operant question here is, Do probiotic mixtures demonstrate more or greater positive health effects than their component strains, when administered separately?

This question has been studied off and on for more than a decade. Studies are often in rodent models, but there are a few human trials also. I’ll spare you the details here and summarize instead. There are 16 studies that compare mixtures with their component strains. In 12 of those cases, the mixture(s) were significantly more effective at improving the studied condition(s). Conditions included irritable bowel syndrome, atopic disease, gut microbiota dysbiosis, inflammatory bowel disease, protection from pathogens, gut function and digestion, H. pylori, and more.

This seems like a compelling case for using probiotic mixtures to treat IBD. However, like in all science, there are some caveats to these data. Some studies did not compare the component strains to the corresponding mixtures using the equal doses (that’s a big one), and some studies found small decreases in efficacy of probiotics that contain multiple genera (like Lactobacillius and Bifidobacteria, for example).

Some studies postulate that Lactobacillius and Bifidobacteria, under certain conditions may be in direct competition with each other, or may inhibit the growth of one another. They recommend probiotic mixtures from the same genera (all Lactobacillius strains, for example). It is notable that the best study which found this effect, still found the mixture more effective than treatment with individual strains.

Oh, what to do, what to do…?

…introduce probiotics slowly and build up to a therapeutic dose of 10+ billion CFU.

First, don’t go crazy trying to find the perfect supplementation method. People around the world have had success with probiotics using many different protocols. Second, think critically about it and make the best decision you know how at the time. Hind sight is always 20/20, so don’t beat yourself up over past mistakes, and try not to get too worked up in the moment–do the best you can with the information you have at the time.

We’ve seen evidence for increased efficacy using mixtures, now let’s look at the major arguments for introducing one species at a time:

You will know how your body reacts to each species or strain (if you use a single strain probiotic).

True, however, if diversity is the gut’s keystone to homeostasis, will one species at a time really get you there? It might; it might not.

For example, if I were restoring a wetland habitat that had been completely changed by invasive species, in the replanting stage I certainly would plant more than one species; the entire suite of natural plants would be appropriate to re-introduce—before invasive species returned (this would seem to argue for FTT as the most appropriate probiotic supplementation plan, but let’s not go there).

It would seem to me that introducing one species at a time would leave uninhabited niche space for other, less favorable bacteria to re-colonize. With that said, I have seen studies which show clinical benefit of supplementing heavily with one strain of bacteria on people with colitis.

Slowly introducing a more diverse suite of probiotic bacteria, on the other hand, would seem to minimize the possibility of the re-colonization of harmful bacteria, or the re-emergence of a pathogenic community (the idea I introduced in the last post), but the point is still arguable.

1. Bacterial Intolerance and the Immune Response to Resident Flora

With IBD, some people’s guts become intolerant of most or all outside bacteria you try to introduce as well as the ‘normal’ resident flora (this seems to have happened to me). The most likely mechanism for this is leaky gut. Inflammation leads to greater spacing between the cells in the epithelial wall, which allows chemicals from resident bacteria to begin to pass through. Over time, your body begins to mount an immune response to these chemicals, thereby building an intolerance to the ‘normal’ resident flora. The only solution for this is to decrease leaky gut by decreasing inflammation.

The keys (the most important components) to doing this, I believe, are dietary changes, antibiotic/probiotic therapy (cycling natural antibiotics with the slow introduction of probiotics), and natural anti-inflammatory compounds. There is more you can do, of course, but these are the keystones.

Either way you choose to do probiotics, the lasting principles are to introduce probiotics slowly and build up to a therapeutic dose of 10+ billion CFU. If you have an adverse reaction, back off, let your system settle, and try again later. Let your body dictate the pace you introduce probiotics.

2. Introducing multiple species (or genera) at a time creates competition between the introduced species.

On the surface, this argument seems reasonable, and is even supported by some studies (mentioned above), but if we use the basic principles of ecology (which I’ve outlined in my last few posts) to think critically about what is going on, significant questions begin to arise. For example, it is true that if those introduced species were in direct competition for the same resources, then competitive exclusion would occur where the fittest organisms would thrive to the detriment of the others. This competition, if it occurs at a significant level, most likely occurs between genera.

With that in mind…

Remember the principle of functional redundancy that I introduced in my last post? This phenomenon has been observed in colonic bacteria, and gives rise to a slightly different picture. Because many of these bacteria (Lactobacilli included) have overlapping function, resources, instead of being exclusionary, are partitioned and bacteria thrive by using different functional mechanisms. This is why, in a healthy person, one can introduce many different bacteria at one time, and see them all survive.

I can envision a scenario where competitive exclusion could be observed in vitro, in a lab (due to the reduction in environmental complexity and resources), but from observations of human gut bacteria in vivo, I don’t think it’s worth worrying about.

I’ve not seen any compelling evidence that direct competition between either species or genera occurs at a significant enough level to reduce the potency of a diverse probiotic supplement below that of a single-strain probiotic.

…there may be more than one prudent way to introduce probiotics into your treatment plan, and at some point, diversity must be a part of that plan.

Treatment: How many and how often should I take them?

I think it’s fair to say that this question is still up for debate. In my mind, if the goal of supplementation is to alter the composition of your flora, then one must ingest enough bacteria to: (1) ensure you get the benefits of the species with which you are supplementing; (2) assure the suppression of species that cause inflammation.

What we’re looking for here is the minimum therapeutic dose (the minimum dose needed to produce the desired effect). In IBD, this is the minimum colony forming units (CFU) to ingest which will provide positive, therapeutic effects on the gut. This dose will depend on the amount and type of bacteria that compose your flora. Certain bacteria are more persistent, better competitors than others. It will depend on your body, your immune system, your diet, your past history, what medicines and supplements you’re taking, and what and when you take them. Thus, the dose that gives you the best results will differ from your neighbor; each person’s minimum effective dose will be different. And it’s up to you to figure that out.

Sounds like catching the wind, right?

A general rule of thumb is to slowly (very slowly) work your way up to about ten billion CFU, all the while tracking your symptoms (always track your diet too). I’ve seen minimum therapeutic dose estimates range from six billion CFU (too small in my opinion), to 20 billion CFU. There may be other ranges out there, but I haven’t seen them yet.

Remember, never take the information in this blog (in any blog for that matter) as THE definitive word. Search, read, and take what I give you in context with what others are suggesting.

I take a stair step approach to finding the minimum therapeutic dose (see Figure). Once you have safely worked up to ten billion CFU (without exacerbating your symptoms), stay there for about two weeks, noting your symptoms. I suggest it this way because ten billion CFU is the most commonly mentioned therapeutic dose I could find. Hopefully, this means that the majority of people will find at least some benefit from this dose level; however, IBD is often enigmatic, so you may need time to assess if this is a proper therapeutic dose for you. Hence, stay at that dose for some time and see if your symptoms improve. If not, and you continue to experience symptoms, up the dosage. This process can take a long time, but patience will be really helpful here. Too much too fast can cause problems (diarrhea, rash, extra gas, etc.). Continue the pattern until your symptoms improve. If you’re tracking your symptoms, this will be easier. Once your symptoms begin improving, stay at that dosage. My minimum therapeutic dose seems to be about 30 billion CFU/day, though I regularly take more.

The above paragraph assumes active IBD symptoms. Once you are healed, the maintenance dose will likely (but not always) be less.

Making Sense of all of This

With all of that said, I still think Jini’s protocol is prudent, even though it may not be as effective as using a multi-strain probiotic. Her method is cautious and tested. The idea here is that there may be more than one prudent way to introduce probiotics into your treatment plan, and at some point, diversity must be a part of that plan.

I spent 18 months on Natren probiotics trying to introduce them slowly, one species at a time, without success. Indeed, I had terrible itching and rashes all throughout that those months, and I had only brief glimpses of solid stools.

I have been on a different, more diverse probiotic for almost four weeks. Though I had itching during the first week, I am now up to 40 billion CFU with no itching at all, and my bowel movements have decreased from 3-4x/day to 1-2x/day. Though they are not yet totally solid, I have noticed less mucus and they are starting to form up a little. My own n=1 experience is more positive with a diverse probiotic than with single strain treatment.

Since our guts are complex ecosystems which thrive on the balance of diversity, eventually I think IBD treatments will have to broaden their probiotic scope. You can do that yourself a few ways:

  1. Make your own fermented foods. Yogurt is easy to make. I have a lactose free recipe in this blog, with detailed instructions. Make your own sauerkraut, it’s even easier than yogurt, but takes 4-6 weeks to ferment. You can make your own kefir, fermented porridges, etc. Check out the book, Wild Fermentation, by Sandor Ellix Katz. It’s a wonderful book, and has recipes and instructions for just about every kind of fermented food you can imagine.
    1. Cost cutting tip: If you are using Natren brand probiotics, and you want to add them to your diet one species at a time, as Jini recommends, then you can save some money by culturing them. You can make yogurt from one single species (though I think it tastes better with more). Use your probiotic (L. acidophilis for example) as a yogurt starter. Add ~10 billion CFU per gallon of milk. You can also ferment vegetables this way, though with vegetables, you cannot guarantee that the species you add to ferment them will be the only species present. So if you are cautious, stick to the yogurt.
  2. Go outside and play in the dirt. For millennia humans have been closely linked to our soils. In doing so, we inhale or ingest lots of bacteria with whom we have evolved. These may not be directly beneficial to our guts, but everything is connected in our bodies, and they can be beneficial in other ways.
  3. Take a diverse probiotic supplement. Ten or more species is a good rule of thumb. Given the data above, it may be a good idea to stick with one genera (Lactobacillius, for example). Some folks will disagree with me, but that’s okay. That’s part of healthy debate. If you’re going to follow Jini’s probiotic introduction plan, then don’t introduce the diverse probiotic until you’ve found your therapeutic dose and have been there for 4-6 weeks. This will ensure that you can accurately assess the effect of the new supplement. If it worsens your symptoms, you can easily remove it.
  4. Stay away from probiotics with yeast initally. People with IBD are especially susceptible to yeast problems. Do not consume yeast until you have been symptom free for 4-6 months at least.
  5. Try Fecal Transplant Therapy. This therapy harvests the full spectrum of bacteria from a healthy person (yes, poo), and transplants it directly into the colon of someone with IBD. For details, see my intro post here, and my summary post here.

Next time, I’ll wrap up the series on probiotics. As always, I welcome your thoughts and comments below.

 

Onward to Health.

References:

Chapman, C.M.C, et al. 2011. “Health Benefits of Probiotics: Are Mixtures more Effective than Single Strains?” Eur J Nutr 50:1-17.

Little, Ainslie E.F., et al. 2008. “Rules of Engagement: Interspecies Interactions that Regulate Microbial Communities.” Annu Rev Microbiol 62:375-401.

Ley, Ruth E., 2006. “Ecological and Evolutionary Forces Shaping Microbial Diversity in the Human Intestine.” Cell 124: 837-848, February.

Qin, Junjie et al., 2010. “A Human Gut Microbial Gene Catalogue Established by Metagenomic Sequencing.” Nature 464:59-65. March.

Falony, Gwen and Luc De Vuyst, 2009. “Ecological Interactions in the Human Gut.” In PREBIOTICS AND PROBIOTICS SCIENCE AND TECHNOLOGY, Chapter 16.

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Filed under: Probiotics • Treatments

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