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Probiotics: it may not all be positive

We are learning more and more about the importance of the microbiome and the links with various diseases. However, the consumer is already bombarded with products, claims and messages about probiotic supplements and foods. This industry is booming, it was worth an estimated 13 billion USD in 2013 and is growing exponentially. Probiotic supplements have become a major force of the functional foods industry that is projected to reach 64 billion USD by 2023 (1).


Infographic of probiotic supplements

Probiotics overhyped?

If we were to believe the popular media, probiotic foods and supplements seem to have become the answer to all questions. But the massive amount of information and positive messages about the benefits of probiotics overshadows the fact that evidence is limited in most areas. In some areas where there is some evidence, the conclusions may be very specific to the context in which they were used. That context is then conveniently ignored when product claims are made.


For example, when probiotics were used in a very specific population it will be impossible to extrapolate to all populations, or if certain strains of bacteria were used, this doesn’t mean that all strains are effective and so on. The gut microbiome has a very important role to play and it changes the way we think about food. Everything we eat is not just food for our body, but also food for our microbiome, and this impacts our health.


Regulation of probiotics

In addition to inaccurate, or at least premature promises and exaggerated claims, regulation of probiotics is inadequate. Regulation of probiotics is also different in different countries. This means that what we think we get, is not always what we actually get. Bacteria in a product we buy, may not be alive, for example. It's a common issue that many products do not have the CFUs (colony-forming units or the amount of living bacteria) reported on the label. Then there is the often used argument, if it doesn’t work, it doesn’t do any harm either. This statement may not be true either as we will explore here. Even dead bugs can still interact with the immune system in the GI tract. Is this potentially problematic? Maybe not, but it's an important consideration. We will have a critical look at the darker sides of probiotics in this blog.


It's a common issue that many products do not have the CFUs (colony-forming units or the amount of living bacteria) reported on the label.

Definition of probiotics

The definition of probiotics is “live organisms which when administered in adequate amounts can confer health benefits to the host”. This definition is from the United Nations (UN) and World Health Organisation (WHO) and dates back to 2001. In reality, however, the term probiotics is used much more widely and there are many probiotic products on that market that do not meet the criteria.


The definition of probiotics is “live organisms which when administered in adequate amounts can confer health benefits to the host”

Sources of probiotics

Bacteria with claimed probiotic properties can be found in several foods such as yogurts or in nutrition supplements sold in various forms (capsules, powders, pills). Within these supplements there may be one or more strains of bacteria. The most common and most studied are the Lactobacillus and Bifido bacterium species. It is generally accepted that these bacteria are likely to provide some health benefits including normalisation of disturbed microbiota, regulation of intestinal transit and production of short chain fatty acids (see these previous blogs for more information):


Probiotic effects are often species and strain specific

However, it is also clear (but often ignored) that many effects are species specific, and in some cases even strain specific. It is also obvious that the dose matters. If studies have demonstrated an effect with a certain dose, it doesn’t mean we will see a similar effect with a different dose. A single strain can have multiple benefits, but no strain will have all benefits. In addition, if we combine strains, they may affect each other’s action. Claims therefore should be very specific to the species, the strain(s), the combinations of species and strains, as well as the amounts of certain species or strains. It has even been demonstrated that supplements from different manufacturers, that according to the label were identical, had very different effects on the microbiome. To make it even more complex it is possible that the same probiotic supplement, has different effects in people with different existing microbiome compositions.


Scientific literature on probiotics is sometimes difficult to interpret

There are also some issues with the scientific literature where data are sometimes difficult to interpret because of methodological issues including reporting of probiotic viability, storage conditions, sample size, dietary practices, demographics, and safety data. For example studies have provided probiotics but not checked whether the bacteria were alive.

These methodological issues have been discussed in more detail by Mohr et al (2).


Why probiotics may or may not be safe

Antibiotic resistance is one of the biggest threats to global health today. It also affects food safety. The bacteria we need protection against are becoming resistant to antibiotics and a growing number of infections are already becoming harder to treat. Infections like pneumonia, tuberculosis and salmonella are more difficult to treat because the bacteria responsible for these infections are becoming resistant to our antibiotic treatments.

Researchers have warned that probiotic supplements could accelerate this process.


There is a significant body of evidence that demonstrates the antibiotic resistance of probiotic bacteria from food. We know relatively little about the effects of probiotic supplements, but it is likely that these effects are larger and more impactful because of the much larger doses of probiotic bacteria.


It has been argued that dietary supplements containing such high concentrations of probiotics represent an excellent condition for the spread of what is called resistant determinants. The term resistant determinants is a generic term to include resistant genes and mutations that give bacteria the ability to resist the effects of drugs. Many of these resistant determinants have been attributed to a transfer event rather than a mutation. It is thought that these events are more prevalent in an environment with large amounts of probiotics in close proximity to pathogens in the human gut.


In conclusion, probiotics and specifically the lactic acid bacteria are generally safe. However we must also be aware of the potential transfer of resistance genes from probiotics to the gut microbiome and eventually to pathogens. This could pose very serious clinical ramifications for the future including resistance to antibiotics.


Summary

The microbiome is important and trendy! Probiotics may play a role and since we live in a society where consuming supplements is considered a norm, a huge supplement industry is being built on the back of limited understanding of the role of the microbiome and probiotics. Some positive effects have been seen but we must be aware that there might be negative effects of probiotic supplements as well. And that some of these negative effects could have severe long-term implications, and we should not let the current hype overpower the evidence (or lack thereof) and the possible negative effects. “Proceed with caution” instead of “Supplementing as a quick fix to all problems”. What is clear is a generally balanced diet with many whole foods is an important modulator of GI function and the gut microbiota.


Reference

  1. Zheng, M., Zhang, R., Tian, X., Zhou, X., Pan, X., and Wong, A. (2017). Assessing the risk of probiotic dietary supplements in the context of antibiotic resistance. Front. Microbiol. 8:908. doi: 10.3389/fmicb.2017.00908

  2. Mohr AE, Pyne DP, Silva G, Leite F, Akins D, Pugh J, A systematic scoping review of study methodology for randomized controlled trials investigating probiotics in athletic and physically active populations, Journal of Sport and Health Science, 2022

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