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30 Nov 2019
In February earlier this year a very interesting research paper was published which summarised an expert panel discussion held at the International Scientific Association for Probiotics and Prebiotics (ISAPP) Annual Meeting in Washington DC in May 20151. We've summarised their conclusions, as well as framed the larger debate.
The ISAPP discussion centred on the definition of a prebiotic, (You can read more on 'What are prebiotics'). As is common in any field of work, as time progresses bringing with it new knowledge, definitions evolve. The publication is a nice example of this. It describes how the term ‘prebiotic’ in relation to the gut microbiome was coined twenty years ago and since then various organisations have put forward their stance on what a prebiotic actually is. These definitions have included referring to prebiotics as non-digestible carbohydrates, which initiate changes in the composition of the gut microbiome, and selectively feed friendly bacteria, and in most cases prebiotics are thought to have a positive overall impact on gut health, you can read more on 'The Microbiome'. Fructooligosaccharides (FOS) is a type of prebiotic, and generally the most commonly found type of prebiotic in supplements in the UK and worldwide.
The paper does not aim to correct any of these definitions with a final and conclusive new definition of a prebiotic; instead it points out that with recent advances in research bringing better techniques for scientists to identify and measure microorganisms, we can now see more comprehensively the changes that take place in the gut microflora, when prebiotics are eaten, and this means that we should be more open to the possibilities of what a prebiotic is.
It’s suggested that by looking at the research we widen our scope in terms of what a prebiotic is as an ingredient (many more complex carbohydrates used in the food industry are now being shown to have possible prebiotic effects). The effects prebiotics have on the gut microbiome, and the way in which prebiotics actually work, are becoming much wider topics of discussion and debate.
Over the years, we have encountered the question of "Does FOS feed pathogens?". When we use the well accepted and most widely used definition of a prebiotic, (that a probiotic selectively supports the growth of friendly bacteria), by definition, the answer is that no, prebiotics will not feed bad bacteria. In light of this publication however, we are taking a fresh look at that definition, and how this might change the way we respond to the question.
First of all let’s recap that a ‘healthy gut microbiome’ is generally considered to be one which consists of a highly diverse array of bacterial species and strains, with a high ratio of friendly bacteria over harmful bacteria. So in a healthy gut there will be some pathogens (bad bacteria), but providing the levels of friendly bacteria outweigh them, this should not compromise good health - in fact this is considered optimal. Balance is the key.
Let’s now look at the negative stories which have circulated in the industry surrounding prebiotics. Generally these reports tend to be along the lines of ‘FOS feeds pathogens’ with not much further explanation of how this statement is backed up by research, or what it could mean in the context of health. It is tempting to assume this must be a 'bad' thing, and unfortunately this haste has led some to turn against FOS.
The origin and interpretation of these statements is unclear, but from what we understand, there are some blog posts online which caution against prebiotics for the reason that they feed the growth of pathogens. One such website – Breaking the Vicious Cycle - claims:
‘Recent studies have shown that Inulin/FOS encourages the growth of Klebsiella, a bacterium implicated in Ankylosing Spondylitis and increased intestinal permeability.’
This sentence is not referenced in the text but there is a list of references at the end of the article. Interestingly, most of the references link through to publications describing the positive effects of prebiotics on the gut microbiome and health. There is one reference however for a publication published in 2000 in Russian, and at present we only have access to the abstract2. The abstract describes an in-vitro study looking at how inulin influenced the activities of various bacteria including Salmonella, E. coli and Klebsiella. Whereas the activity of Salmonella and E. coli was restricted by the inulin, it appeared to increase for the Klebsiella. A search for other studies investigating the effect of inulin and other prebiotics on pathogens including those in the Enterobacteriaceae family such as Klebsiella, shows that some Enterobacteriaceae including Klebsiella do indeed appear to use prebiotics as a food source to grow3
However, we must be careful not to jump to conclusions that this is a ‘bad’ thing and look at the bigger picture. We started off by recapping the mantra by which many things in life, including the gut microbiome, have in common: balance is the key.
Actually, a comprehensive look at the research available, and the willingness to understand this phenomenon in its rightful context shows that although prebiotics may feed some ‘pathogens’ this is greatly outweighed by the rate at which they feed friendly bacteria. For example, a study conducted last year took faecal samples from healthy human volunteers, extracted the microbial content, and then analysed how these samples reacted when inulin was added (a negative control and a positive control (cellulose) were also added to separate samples)4. The results demonstrate that inulin caused Lactobacilli and Bifidobacteria to flourish, and also caused a slight increase in Enterobacteriaceae, the family to which Klebsiella belongs.
However, in the same way that when we look at cholesterol and heart health, we do not fixate on the Total Cholesterol (TC) reading only, but rather view it in the context of the LDL (‘bad’ cholesterol) and HDL (‘good’ cholesterol) - because it gives us a much more accurate picture of what is going on physiologically in the body and the symptoms the individual may experience, as well as predicting the risks they are at* – it is good practise to apply this logic in this situation also.
That is why the authors of this paper analysed the ratio of the Lactobacilli and Bifidobacteria to the Enterobacteria, to give us a better idea of the balance between them. What their results show confirms that we need not be worried about a slight increase in Enterobacteria. This is because their results showed that for every 10 Enterobacteria in a negative control group (no prebiotic) there were 18 Lactobacilli (to 1 decimal place). But when inulin prebiotic was added this jumped to 30 Lactobacilli per 10 Enterobacteria, a 3 to 1 ratio, which is a much healthier balance than without the prebiotic. Similarly, for the Bifidobacteria: Enterobacteria ratio, in the negative control group (no prebiotic); for every 10 Enterobacteria there were 17 Bifidobacteria but when the inulin is added this jumped to 45 Bifidobacteria per 10 Enterobacteria, a 4.5 to 1 ratio, which is again a much healthier ratio. It should be said that this study was carried out in-vitro, and, as always, it’s best to have results confirmed in human clinical trials, but it is extremely illustrative of the argument of balance.
Over the years numerous studies have confirmed that prebiotics seem to have the predominant effect of increasing levels of friendly bacteria in the gut, particularly Bifidobacteria5,6,7. Given the wide range of individual variability, studies have not confirmed an exact rate of change of different genus and species in the gut when different types and amounts of prebiotics are taken. However the overall consistent outcome from the clinical trials is that prebiotics have a positive impact on the gut microflora. We definitely do not see from the clinical research that levels of pathogens flourish to an unhealthy level, actually in most cases the overall pathogen load decreases.
There are a number of theories as to why the pathogen load in the gut decreases as a result of prebiotic supplementation. The main theories are that as friendly bacteria such as Bifidobacteria feed on the prebiotic, acids are produced which lowers the pH in the gut, making it less favourable for the growth of pathogens. Secondly, we know from in-vitro studies that friendly bacteria produce antibacterial substances to 'ward off' the growth of pathogens in their vicinity. Thirdly is the simple theory that friendly bacteria 'out-compete' pathogens in the gut; attaching to the intestinal wall & pushing them out / leaving them less space physically to multiply. A proliferation in friendly bacteria as a result of prebiotic supplementation will increase these three effects further.
Finally, a theorised reason for the temporary symptoms (bloating & gas) experienced by some individuals, when they first take prebiotics, could be that in these cases there may be a lag time for the friendly bacteria levels to out-grow pathogen levels. Until a few days have passed and the friendly bacteria levels are well established, potentially some pathogens are also able to ferment on the FOS, giving the temporary side effects. Pathogenic bacteria produce more smelly gases (such as sulphur gases) which distend the abdomen much more than the gases produced by friendly bacteria (such as carbon dioxide). Without doubt once this short period of time has passed the FOS supplementation is very likely to give benefits for the individual e.g. more regular bowel movements and less bloating. Studies have not proven this is the case, it is simply a theory at this stage.
For the very small number of individuals who seem to be sensitive to FOS even in the long run, this could be a sign that there is a more complex dysbiosis in the gut and it may be advisable to avoid prebiotics (e.g. take a live cultures supplement without FOS or inulin) and consult with a practitioner such as a nutritionist to do some core work on improving the digestive system holistically. Another explanation is that, as with any supplement or medication, not everything suits everybody, so there may be an odd case where the individual has otherwise healthy gut microbiome, but they are just not suited to prebiotic supplementation.
It’s important to consider the full context of a particular health situation; we have particularly demonstrated this in the interpretation of cholesterol readings and in the interpretation of the prebiotic – pathogen relationship. Although some studies, mainly in-vitro experiments, have demonstrated that some prebiotics may feed certain pathogens such as Enterobacteriaceae (e.g. Klebsiella), if we attempt to scale up these test tube experiments to relate the real life scenario in an individual’s gut, the clinical trials do not support this as being an issue for human health. Instead the overwhelming evidence from clinical trials is that prebiotics mainly feed the growth of friendly bacteria, which with continued supplementation tend to far outweigh any additional growth of ‘unfriendly microorganisms’. As friendly bacteria flourish with prebiotic supplementation the pH of the gut decreases, which acts as a natural deterrent to the growth of pathogens, and this coupled with the antibacterial effects of the friendly bacteria themselves, helps to keep a healthy balance of friendly to unfriendly microorganisms in the gut.
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Notes & References:
* Blood test reports for cholesterol markers generally include a TC:HDL ratio, and the lower this ratio (i.e. the higher the HDL) the better. For example if the TC = 5 and the HDL = 1.5 this will give a TC:HDL ratio of 3.3. However if the TC = 6 and the HDL = 1.8 this also gives a ratio of 3.3. Many leading consultants would consider both readings to have similar significance in determining the risk of that individual having a cardiac event. However if we fixate on the TC figure only, many individuals would be unnecessarily worried if they had a TC = 6 compared to a TC = 5.
1. Hutkins (2016) Prebiotics: Why definitions matter. Curr. Opin. Biotechnol; 37: 1-7.
2. Valyshev (2000) The effect of inulin on the biological properties of enterobacteria. Zh Mikrobiol Epidemiol Immunobiol; 1:79-80. (Article in Russian)
3. Hartemink (1997) Growth of Enterobacteria on Fructooligosaccharides. J, Appl. Microbiol; 83, 3: 367-74.
4. Jung (2015) In Vitro Effects of Dietary Inulin on Human Fecal Microbiota and Butyrate Production. J. Microbiol. Biotechnol; 25, 9: 1555-1558.
5.Gibson (1999) Dietary modulation of the human gut microflora using the prebiotics oligofructose and inulin. J. Nutr; 129, (7 Suppl): 1438S-41S.
6. Kolida (2002) Prebiotic effects on inulin and oligofructose. Br J Nutr; 87, Suppl 2: S193-7.
7. Langlands (2004) Prebiotic carbohydrates modify the mucosa associated microflora of the human large bowel. Gut; 53, 11: 1610-6.