The dietary guidelines for IBS have been published. It has taken considerable work to produce these guidelines over the last 2 years at least and I was very pleased to be part of the development process with some very experienced dietitians. The paper on probiotics I was involved in was a really great way of learning about this subject area and also the complexities of developing probiotic products. The perhaps unsurprising result of the systematic review means that the evidence base for these products is not strong enough to allow us to advocate one probiotic product for IBS. However the Ford (2014) review with meta analysis (a calculation used to show whether combining controlled treatment trials are effective) showed that overall probiotics are effective. Wow – conflicting!
The variety of formulation possibilities of a probiotic product means that it would be unusual for a new product to be the same as one that has been previously developed. Heterogeneity of these products is a big problem, imagine you are a manufacturer, you don’t necessarily want to go over old ground as the expense of development and research is high and you want to fund research to showcase your new product. Research in industry is about marketing and the product, you want to recoup your investment.
But repetition is exactly what is needed to strengthen the evidence – more papers showing effectiveness for one product. A generic medication, where choice of how to produce the medication formulation is likely limited by the chemical nature of the active ingredient, perhaps meaning the tablet excipients do not vary overly much. The result is you can have many published papers for one medication, a position of strength. Probiotics, on the other hand, can be added to a food, and should be classed as a functional food, which is chemically complex and varied. Not that I lay the blame solely at the door of the manufacturers, the choices they have when considering new developments are enormous – to include one or many probiotic species, to have a tablet, yoghurt of fruit juice drink? What is the likely shelf life, when do you take it – with food, after or before? Does it survive to the digestive tract? Does it need too? (Enck 2008 denatured their probiotic before its use) What dose to include? (This was tested by Whorwell in 2006 – three doses and only one proved to be marginally effective.)
Are we looking at a food or a medication? As I have stated above probiotics should be classed as a functional food. Randomized controlled trials are a very good method of researching medications, but not necessarily diets, which are overly complex and difficult to randomise. However, this is the best method we have and is a requirement for a good evidence base, so clearly needs to be used.
Confounding variables (a factor that is not under study that can vary and influence the final result) are vital to be considered and ruled out. In probiotic research, when we a researching a food item, we should ensure participants diets do not change and influence the final result. The more understanding we have in how our diets influence our own microbiota, which has improved over the past few years, the more important this variable is becoming to the methodology. So it needs to be considered a part of the methodology and shown not to change throughout the duration of the study.
We have a varying medical condition – IBS, IBS-C, IBD-D, IBS-M and IBS post infection – could these possibly be distinct groups? Treatment for one type of IBS also might result in swinging symptoms to another type – changing bowel function for sure, but the patient feels no better. Quality of life is very important and certainly should be part of the measures used, testing has used a variety of different validated tools to assess this important factor. Also, measuring tools for IBS are often not standardised, all of these factors make for poor results. We also have Rome IV, which has removed the term ‘discomfort’ from it’s diagnostic criteria, reducing prevalence of IBS overnight – it is going to be very interesting to see what effect this has on future treatment research.
Numbers of participants in studies are often low, meaning that the studies should be defined as pilot studies – this results in a positive effect being overly positive (p values will be likely closer to 0.05 for higher numbers of included participants, if you have a p value of 0.001 check out the number of participants – if you have over a hundred this is a good result! If you have 10, maybe not so great.) We do need over 100 patients to make good research in IBS.
We also have a situation where some probiotics that have two RCTs – often with conflicting results, how is this possible? We are likely comparing two ‘moving targets’ both with high heterogeneity – my personal view is that research in probiotics and IBS is a little bit like herding cats – a very big challenge. When herding cats, the method used is vital to the success of the job and probiotic research is no different in this. The methodology, whilst has improved over the last twenty years, needs to be further tightened up, I’m afraid.
One topic that is often mentioned in IBS research, is placebo effect, this is reported to be high, anywhere from 30-50%. So, to know if the product is actually effective you need to test whether the result gives an improvement of over this percentage, from baseline. Not many are. But is this an issue? Maybe not if the patient feels better that is a result, we need to consider the patient in our assessment of the evidence too.
This is where we are, considering the patient. Perhaps the fact we have any studies showing a positive effect is nothing short of a miracle considering how difficult this research is to undertake. Standardizing the process will produce better results and should certainly be considered. Drivers for the probiotic industry are the ability of using a health claim on their product, EFSA have still declined to confer this privilege to any probiotic product. The one manufacturer that does achieve this status is likely to be a market leader, using good methodology is key to this process, in my humble opinion. However we have a duty here to people with IBS and perhaps taking a pragmatic approach is best, as overall the evidence by meta-analysis suggests that probiotics are effective. We should publish where the evidence is best to help patients to choose the best option, if they want to try these products. It might not help all symptoms, but the patient should choose the symptom they wish to reduce and go with the product where the evidence is weak.
My own toe dip into herding the evidence of RCTs into a systematic review proved how much of a challenge this is, numerous hours (immeasurable) pouring over data proved to be a interesting way to learn about these products. Hopefully this effort will result in some improved data and improved results in the future.
If you wish to look at the papers yourself the links are below, and if you are a healthcare professional the probiotics paper contains a really good chart that can be used in a clinic situation. Download your copy today!