There’s a great deal of debate these days about the sometimes wild and often wondrous health claims touted by the probiotics movement. These special beneficial bacteria (mostly lactic acid bacteria like those found in yogurt, and available now it the convenient pill or capsule form) are claimed to not only cure everything including digestive disorders, irritable bowel syndrome, pediatric asthma and allergies, but are also said to be capable of preventing a wide variety of problems including acne, eczema, vaginitis, halitosis, and even cancer. Those skeptics (realists?) among us realize this is most likely impossible.
I, of all people, would love to believe that just hand-full of species of beneficial bacteria, when ingested on a regular basis, can make the sick well, heal our wounds, lower our blood-pressure, and bolster our immune systems, but that’s the stuff of science-fiction fantasy and all rather outlandish.
Or is it?
I posted a few weeks ago about a clinical trial using lactic acid bacteria (like those found in yogurt) to help mice stave off flu symptoms and found I had unwittingly placed myself on the side of the argument with the “snake-oil salesmen” and moneymakers (aka, commercial probiotics salespeople). I do love to play devil’s advocate on occasion, so I began looking into the subject a bit more… where do all these various and sundry health claims come from? Are skilled marketing strategies simply playing on the human desire for a cure-all, a fountain of youth, or is there some seed of legitimacy at the base of it?
On my quest for truth, I found first, the report by the American Academy of Microbiology, “Probiotic Microbes: The Scientific Basis”… a must-read for any truth-seeker on this subject. However, since the time it was put together (November 2005), the myriad of health claims being made in the media (as well as the backlash against) has vastly expanded, and science did not have a grasp of precisely how this all worked within the human body.
Which brings us to my second discovery in my quest: a truly seminal research study which (finally!) very clearly indicates how probiotics modulate human cellular pathways to achieve several varied, and perhaps unexpected, health benefits. The article by van Baarlen and colleagues (full citation below) was actually published online in the Proceedings of the National Academy of Sciences the same week I made my original post on yogurt bacteria (Sept 7, 2010).
The study involved seven healthy, non-smoking adult human volunteers and the transcriptional responses (meaning, which genes were being actively expressed) of their stomach mucosa to consumption of live cells of Lactobacillus acidophilus, L. casei, L. rhamnosus, or a placebo control. Every volunteer was exposed to each of the four treatments, with a two week break, or rest period, between treatments.
The first discovery was that the gene expression profile of each of the volunteers was considerably different, regardless of treatment. Of course, this reflects the fact that we are each individuals and our health and well-being is a sum of our genetic make-up, our environment and experiences. But the implications are clear when we consider the conflicting results of many of the probiotic clinical trials. Natural variation of genetic expression between individuals is high enough to mask the observed clinical effects in some people while not in others, especially when combined with the different effects of each bacterial species.
This brings me to the second major discovery: the fact that each of the bacterial species tested had significantly different effects on the mucosal gene expression profile (GEP) of each volunteer. By this, I simply mean the following:
- L. acidophilus elicited changes in genes involved in stimulating and regulating immune response (both innate and acquired: increased interferon and antibodies), and hormonal regulation of water and ion homeostasis, increased tissue growth and wound healing, and metabolism regulation.
- L. casei lead to gene expression regulating the balance between innate and acquired immune response, as well as metabolism regulation and regulation of hormones involved in blood pressure.
- L. rhamnosus caused expression of genes involved in wound repair and healing, innate immune response (interferon), and ion homeostasis.
All three bacteria stimulated responses involved in innate immune response, while L. casei also caused modulation (balance) of the innate vs. acquired immune response. The authors noted that the response to each species of bacteria was markedly different, and that these differences could extend as far as the growth stage of the bacteria in the probiotics preparation. What this means is that every probiotics product on the shelf is not created equal; the species, even variety, is important, and the methods used to cultivate and preserve the organisms may be important as well (i.e. live cultures are best).
Because of the fact that the technology used in the approach for this study is fairly new, we actually don’t have a lot of human mucosal gene transcription profiles to compare these types of data against (in other words, we can’t see how these data align with other data from similar studies, because there are not yet any other similar studies). So, my first thought was something along the lines of, “How do we know the same GEP might not be elicited if somebody ate food, or anything for that matter?” The authors expected questions like that and therefore compared their data with data from GEPs of human cell lines exposed to various compounds. The results of this comparison were quite interesting:
- L. acidophilus had similar effects to drugs for hypertension, convulsions, and inflammation.
- L. casei caused had similar effects to drugs used to treat muscle hypertension, water retention, and inflammation.
- L. rhamnosus elicited effects similar to drugs used against protozoan infections and to amplify bowel movements.
So, not only could they directly measure certain genes in the human stomach mucosa responding to the probiotics in a way that suggested modulation of the immune system (amongst other things) but the response was actually similar to the effects of drugs engineered to treat and modulate that very thing. Fascinating!
This study is obviously not the end-all and be-all of probiotics work, but it’s a huge piece of the puzzle in terms of why probiotic clinical trials have yielded such conflicting results, and particularly how probiotics modulate the immune system in a variety of ways and against a variety of afflictions. It certainly supports the mouse-flu study I blogged a few weeks ago. The authors conclude,
“We anticipate that responsiveness to probiotics is not only determined by characteristics of the consumed bacterial strain but also by genetic background, resident microbiota, diet, and lifestyle. This study could, therefore, be among the first steps to investigate the interplay between microbiota, probiotics, or other nutritional supplements and human genetics tow personalized nutrition.”
To me, this says that if you already have a healthy immune system, you work-out and eat right, get enough rest and all that, you might or might not notice a difference from taking a probiotic. However, if you’re immune system is already compromised, you regularly drink, smoke, are largely sedentary, and stay up all night doing who-knows-what… if you opt for a cup of yogurt instead of a Twinkie, you just might thank yourself in the morning (and now we have the data to prove it!).
van Baarlen P, Troost F, van der Meer C, Hooiveld G, Boekschoten M, Brummer RJ, & Kleerebezem M (2010). Microbes and Health Sackler Colloquium: Human mucosal in vivo transcriptome responses to three lactobacilli indicate how probiotics may modulate human cellular pathways. Proceedings of the National Academy of Sciences of the United States of America PMID: 20823239