May 16 2016

Review of Probiotics

probioticsThe idea behind probiotics superficially sounds reasonable – friendly bacteria are important to the functioning of our gastrointestinal (GI) system and immune system. Probiotic products are supposed to supplement those friendly bacteria with live bacteria from certain foods, such as yogurt, or even in capsules.

A recent paper, however, reviews studies looking at probiotics in healthy subjects, finding no evidence for benefit. Let’s take a close look at this study and the science of probiotics.

The systematic review focused on studies looking at the change in the composition of bacteria in feces in healthy adults taking probiotics compared to placebo. They found:

Seven RCTs investigating the effect of probiotic supplementation on fecal microbiota in healthy adults were identified and included in the present systematic review. The quality of the studies was assessed as medium to high. Still, no effects were observed on the fecal microbiota composition in terms of α-diversity, richness, or evenness in any of the included studies when compared to placebo. Only one study found that probiotic supplementation significantly modified the overall structure of the fecal bacterial community in terms of β-diversity when compared to placebo.

The definition of α-diversity is the mean difference in species in a specific location, while β-diversity is the difference in species between two different locations.

The bottom line is that there was no consistent effect among these seven studies. The studies were all relatively small, from 21-81 subjects, and were rated medium to high in terms of overall quality. It is fair to say that there is probably no clinically significant effect, given these negative studies, however an effect too small to be seen in studies of this size cannot be ruled out without larger studies.

There are also other ways to track the alleged benefits of probiotics, such as looking at specific health outcomes like weight control, diabetes, and the risk of autoimmune disease. A 2015 systematic review of probiotics for weight loss showed no benefit. However another 2016 review concluded there was evidence for a small benefit, although it seems they used a lower bar for including studies.

A 2014 review found some evidence for benefit in lowering blood pressure. There may also be benefit for glucose metabolism.

However, this research is generally preliminary and effect sizes are small. Further, the fact that probiotics do not seem to change the intestinal microbiotia does call into question any clinical benefits (although does not rule them out).

The best evidence exists for probiotics for antibiotic-associated diarrhea. This makes sense, because the problem is too little friendly bacteria in the GI system. A recent review found:

Based on this systematic review and meta-analysis of 23 randomized controlled trials including 4213 patients, moderate quality evidence suggests that probiotics are both safe and effective for preventing Clostridium difficile-associated diarrhea.

Plausibility of Claims for Benefit

Here is a typical list of claimed benefits from probiotic products:

Support immune system, improve digestive function and mineral absorption and aid in healing leaky gut*

Improve skin health, acne and dry red flaking skin, Kills candida and bad bacteria,*

Enhanced synthesis of vitamin B12, calcium and vitamin K2, Support digestion of difficult substances like gluten and lactose.*

These are classic “structure function” claims that are not reviewed by the FDA. They are not supported by good evidence or any evidence at all in some cases.

Does it really make sense that eating live bacteria can affect your health? The plausibility of this claim may be more complicated that originally thought. It seems that the microbiome exists as a stable ecosystem of about 100 species of bacteria. Eating extra bacteria does not seem to impact this stable ecosystem.

This does not mean it’s impossible to do so, but it likely takes more than eating yogurt. We may need to use something more radical, like a fecal transplant. Essentially we need to transplant another stable ecosystem. Or we may need to consume dozens of species in high colony counts over an extended period of time.

Even if we could make permanent changes to the microbiome, it is not clear if this is an effective health intervention. Right now we have data that correlated certain types of bacterial environments with certain health states, like diabetes or obesity, but the cause and effect is not clear.

Conclusion

The current state of probiotic science is best described as preliminary. Clearly the gut microbiome is important, and is integrated into the whole organism. There are interesting correlations with various microbiome ecosystems and various states of health and disease. There are plausible mechanisms by which the microbiome might affect health.

However, the research has not yet advanced to the point that we know how to significantly or reliably affect that microbiome. The most recent review suggests that current probiotic products are not having any significant effect on the microbiome, at least in healthy individuals.

This is an area, like stem cells, that is likely very promising, and there is some preliminary suggestion of possible benefit. However, preliminary evidence has a very poor track record overall of panning out to actual benefits. It is too early to tell how the science of probiotics will play out. I suspect that any real health benefits will only come once we have fairly sophisticated and aggressive methods for making specific changes to the long term ecosystem of the microbiome. Real benefits may also only come once we incorporate genetically modified bacteria into the mix, with specific properties designed to affect health.

We also appear to be at or near the point of maximal hype. This is a pattern often repeated. Right now there is lots of hope and speculation that manipulating the microbiome will have potential benefits. The research is largely preliminary, which tends to be false positive. This situation is ripe for exploitation by companies to sell supplements with claimed or suggested benefit, before the research definitively shows that such products have little or no benefit, or that the situation is more complex than we thought.

We were here 20 years ago with antioxidants, for example, and 10 years ago with stem cells. Now it’s probiotics’ turn. There will always be something.

Still, altering the microbiome as a health intervention has promise, but it may be 10-20 years before we have real science-based interventions.

Further, it may not be necessary or helpful to alter the microbiome in a healthy individual. They may already have an optimal microbiome. More is not necessarily better.

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