Herding cats – the challenges of probiotic research in IBS.

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!

 

Why your wind smells of roses – The Life of Poo book review

Well now, a book all about poo, why would anyone want to read this you may ask, surely the grim subject of poo is not something to read about – certainly not in public or polite company, I imagine you thinking. This thought briefly entered my head as I picked up the book in the bookstore and I do confess, even as a professional working in the area of digestion and more than happy to talk about poo in clinic, I purchased it online – it came in a brown package. If you are wondering whether to read on – this is not a post for those with a ‘delicate’ disposition (who perhaps belong in the eighteenth century) or one to read on your tablet at the breakfast table. You have been warned.

It might surprise you to know, you really ought to read this book. How can I persuade you to take a quick peek? How about the post title? Have you ever said, with an air of superiority, ‘my wind smells of roses, that smell cannot possibly be down to me’? You are correct it seems, at least in very small doses anyway. The ‘flower’ odour usually appears at much lower doses than is produced by a ‘silent but deadly’ however, but I’d bet you didn’t expect that did you? Adam writes that skatole and indole, the gases found in malodorous wind, smell of flowers in small concentrations.

A very surprising incident happened whilst out walking yesterday, my hubby stated this very fact when smelling hawthorn blossom. Wow, I thought, how does he know that? I really couldn’t believe it, I had only read this fact in Adams book the day before.  Well the story behind his knowledge is a bit more grim than Adam’s fascinating publication. So now I have told you about my husbands experience you want to know about it, don’t you? My husband is a chemist, he worked in a company making pharmaceutical products, one of which utilised the chemicals indole and skatole – “oh, good grief”  I exclaimed, “what sort of pharmaceutical product uses those?” “dog trainer liquid” was the response – the mind boggles. My husband had the unfortunate experience of contaminating his lab coat with these very chemicals and not only that, then proceeded to wander down to the restaurant in said lab coat, at lunch time. Chaos ensued, this had the effect of teaching him the very good lesson of removing his lab coat before dining, which one should always do, to prevent ingestion of nasty chemicals and nauseating diners. He showed absolutely no sense of embarrassment though, surprisingly enough and regaled the story with a good degree of relish.

Now, back to the topic in hand. This book is factually correct, very amusing in places and does have a small reference to irritable bowel syndrome and inflammatory bowel disease in it’s chapters – something for everyone then! It discusses the microbiota, antibiotics, prebiotics, probiotics and the microbiota’s relationship with health and disease. Very topical and containing everything of interest to me. I really like the examples used in the book to describe some complex concepts in simple easy to read form. If you want to know more about poo – yes you really do, think of it this way, it’s like looking in the bowl before flushing, you know you really should (but DO put the lid down before the flush, read a lot more about that in the book) – then I can’t think of a better book to buy.

 

This book was purchased by myself.

Reflection on a year of blogging.

IMG_1650I have just had my anniversary of my blog, I started the site a year ago and did wonder how it would go, but I have been really hooked on writing and cooking recipes. Watching my stats I am also surprised at the breadth of countries who are interested in looking at my site, plus an interest in which countries have not viewed my site yet – so, come on guys I want to complete the full globe this year, as sure as anything you can bet that someone has some digestive complaint that would benefit.

I have experienced writers block for the last month and a paucity of recipes too. I am hoping that IBS Awareness Month spurs me on with writing more and I would also appreciate some ideas about what people would like to read on digestive disorders. The plans for the next twelve months include more book reviews and recipes, I hope to expand the blog to a website – and perhaps most exciting of all I hope to be running a clinic for patients who have intolerances, allergy and low FODMAP dietary requirements very soon, email me if you are interested.

http://www.arikhanson.com/wp-content/uploads/2010/08/InspirationPoint.jpg

I have attended The IBS Networks AGM today, my third one and the future in IBS is looking really positive, new ideas, treatments (including the Low FODMAP diet) and new research into the gut microbiome (bacterial population) and it’s effects on health and disease have made IBS more of an attractive area for research and medical management. If you are interested in getting involved, maybe you would be interested in running a support group in your area, The IBS Network can provide support if you do.

ibsnetwork

So watch this space and any ideas on what you would want to read are gratefully appreciated!

Probiotics, into ‘au natural’ or domestic goddess? Want to make your own? Check this post first!

Kombucha fermented tea

Probiotics have been around for millennia and are found naturally in certain foods, however does natural always mean safe? This post discusses the various types of probiotics that are home-made and discusses their safety and whether they will actually do what they propose to. This post has been rather challenging to write, it has produced lots of information, but little in the way of clinical evidence to directly prove that home-made products are more or less effective than shop bought, and little direct evidence in how effective they are at reducing gastrointestinal problems. This is perhaps not too surprising.

Home cultured dairy foods including yoghurt, cheese & clabbered milk.

There is nothing wrong in producing your own home-made yoghurts and cheeses, should you wish to. Kits are available on the internet and you may also wish to go on training courses, or review books to get started (will probably help to avoid costly mistakes!) Milk, if left un-refrigerated will sour, some types of milk will take longer to do this depending on the amount of bacteria they contain and the processes they have been exposed too, UHT milk contains very limited numbers of bacteria due to its heat treatment, so it will take longer to sour, for example. Starter cultures are required and can be purchased for this very process, but other ‘live’ milk products can be used as starters.

Kombucha

Kombucha is a Japanese fermented mushroom in tea and sugar, proposed to be taken as a tonic. It contains yeast and bacteria and is anecdotally suggested to reduce constipation and have benefits for myriad of other health complaints. Web & Pinterest searches revealed lots of information about how to make this at home, but it is also available to purchase as a manufactured product. A small number of case studies have reported serious side effects with taking this product as a drink, some of the cases had other medical problems which may have also been implicated, but symptoms have been reported in people who had no health problems too. Kombucha has resulted in jaundice (yellowing of skin and eyes due to damage to the liver,) one case had improvement to the liver after stopping taking kombucha, but one death was mentioned that was attributed to taking this product. We have no evidence that Kombucha improves constipation and although cases of serious side effects are rare and the data is old, it is probably worth avoiding taking home made kombucha as a health tonic, liver damage is a very serious problem that is best avoided. If you do wish to try komucha perhaps try the manufactured products but no evidence is available to suggest it helps with IBS for example.

Sauerkraut

Sauerkraut is a fermented vegetable product based on cabbage its direct translation is sour cabbage! It has reported both prebiotic (food and homes for bacteria) and probiotic actions. It is also a source of vitamin C, which helps your skin, and sauerkraut was used in history as food in winter to prevent scurvy. Sauerkraut also contains a substance called tyramine, some people have problems with tyramine and are informed to avoid this (MAOI diet,) – you will likely know, if you need to avoid this food!!

Sauerkraut has been produced and consumed in European countries for approximately 1000 years, and is widely available as a manufactured product in supermarkets. The bacteria that are found in sauerkraut are lactic acid bacteria and these produce an acid environment leading to its sour taste. When produced correctly it can be kept for several months in an airtight jar but as with all home-made products the possibility of producing pathogenic bacteria should be considered, the not so friendly ones, that can result in illness. unpasteurized (or home-made) varieties will contain more probiotic activity but hygiene and use of a reliable manufacturing method, is very important. Listeria has been found during fermentation of sauerkraut, therefore it may be advisable not to consume unpasteurized sauerkraut during pregnancy or also those people who may be at risk of illness such as those with weakened immune systems, or the very young & the elderly.

Their may be one drawback to this food for your gut, as a consequence of it containing some prebiotic features, due to it being based on cabbage. If you find eating foods containing oligosaccharides (a starchy prebiotic found in beans, cabbage, sprouts, for example!) results in intolerable gas and bloating, then sauerkraut is probably best avoided. But white cabbage has been tested and is low fodmap so sauerkraut based on white cabbage is likely OK to use but do check for other ingredients. However it is a dish that is readily available and is worth eating, if you like it. As for its effectiveness in promoting gut health a search on PubMed (published research papers) did not reveal any direct studies on the effectiveness of this product on gut health, but lots of data on the populations of bacteria and yeasts found in sauerkraut, so an indirect link may be possible, but as with most traditional foods, direct evidence is elusive and needs to be investigated.

Kefir

On a basic Pubmed search an incredible 1,912 studies that mention kefir were found, so for a home manufactured product it seems to have attracted the attention of the scientists and clinical researchers! However in IBS for example non of these research papers have been reviewed systematically, therefore they are likely to not meet the strict criteria for good levels of evidence such as randomised controlled trials. Kefir is a stable cultured dairy product that contains yeasts and lactic acid bacteria of various different types, thirty bacteria species and 15 species of yeast have been identified. It can be purchased as a starter called Kefir ‘grains’ for producing live dairy products at home. Kefir has a large number of bacteria that are suggested to be able to pass into the gastrointestinal tract in beneficial numbers despite passing through the acidic conditions of the stomach (not all bacteria will survive to the small bowel.) It has even been used successfully to replace yeast in producing bread, as a consequence of the yeast species it contains. It is reputed to improve lactose intolerance (increased gas, bloating & diarrhoea when consuming lactose, a sugar found in dairy products) due to the lactic acid fermentation process, but many yoghurts and cheese have lower levels of lactose as a result of fermentation. It is probably best to introduce this food slowly and monitor you symptoms, if you are prone to lactose intolerance and wish to try it. A recent review reported that kefir is an important food and warrants further study, although this review had most of the data from animal studies and in vitro studies (studying the activity in cells, or in test tubes) so the research cannot be related directly to effects in humans. It is certainly and interesting product and does warrant further studies!

Filmjolk

This is fermented milk and is similar to Kefir, it is made using different bacteria lactococcus lactis and Leuconostoc Mesenteroides, and this gives the yoghurt a different taste – less sour than traditional yoghurts. It is also available commercially; searches have not produced much data in English about whether this product is goof for digestive health but if you can read Swedish follow the link to learn more (lots of papers at the bottom of the page)

http://en.wikipedia.org/wiki/Filmj%C3%B6lk

Tofu miso

These are fermented soya foods that do contain bacteria however don’t forget that bacteria may be affected by the cooking process, so how useful the probiotic effect is when these products are exposed to heat, is debatable.

As with all food preparation, food hygiene is vital to produce safe home-made products, ensure you use clean utensils, wash your hands and check the following link:

http://www.nhs.uk/Livewell/homehygiene/Pages/how-to-store-food-safely.aspx

http://www.nhs.uk/Livewell/homehygiene/Pages/Homehygienehub.aspx

Some people are possibly more at risk from taking live products, during pregnancy UK advice is to avoid products containing unpasteurized milk, and soft cheeses that are mould-ripened, such as brie, camembert and chevre and others with a similar rind. Other cheeses you need to avoid are soft blue-veined cheeses such as Danish blue or gorgonzola. These are made with mould and they can contain Listeria, a type of bacteria that can harm your unborn baby. Also if you have been told by your doctor that you have a weak immune system (medically called immunocompromised) you are better to avoid taking live bacteria and food products that contain them.

http://www.ncbi.nlm.nih.gov/pubmed/21390946

Niksic M, Niebuhr SE, Dickson JS, Mendonca AF, Koziczkowski JJ, Ellingson JL  (2005) Survival of Listeria monocytogenes and Escherichia coli O157:H7 during sauerkraut fermentation. JFood Prot. Jul;68(7):1367-74.

Srinvisan R, Smolinski S, Greenbaum D, (1997) Probable gastrointestinal toxicity of kombucha tea J Gen Intern Med 12:643:644

Hertzler, S.R. and Clancy, S.M. (2003). Kefir improves lactose digestion and
tolerance in adults with lactose maldigestion. J. Am. Diet. Assoc. 103:582–
587.

ZEYNEP B. GUZEL-SEYD˙IM1, TUGBA KOK-TAS1, ANNEL K. GREENE2
and AT˙IF C. SEYD˙IM1(2011) Review: Functional Properties of Kefir. Critical Reviews in Food Science and Nutrition, 51:261–268

Oggioni MR, Pozzi G, Valensin PE, et al; Recurrent septicemia in an immunocompromised patient due to probiotic strains of Bacillus subtilis. J Clin Microbiol. 1998 Jan;36(1):325-6

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Probiotics – what are they and can they help my gut?

There is a plethora of information about probiotics and we are constantly bombarded with advertisements promoting their use, for gut health, so what should we believe? Probiotics are products or food that contain bacteria, in large enough amounts to alter the number and/or type of bacteria that live in the large intestine (see diagram at the bottom of the page.) Everyone has populations of bacteria in their gut and we know that changes to these natural populations can occur in food poisoning or with any illness that occurs within the digestive tract. This could be irritable bowel syndrome, crohns or ulcerative colitits for example, but other disorders can affect the populations of bacteria. We are only just beginning to understand how these bacteria affect our health; they produce substances called short chain fatty acids from starchy foods, which help feed the digestive tract, keeping it healthy, a real benefit. They also help to produce vitamin K, a vital nutrient that helps our blood to clot and our bones keep healthy. So the relationship with our bacteria is beneficial for both the bacteria and us. These ‘good bacteria‘ also help to prevent some of the more harmful bacteria from developing and causing illness. Our bowels contain huge numbers of bacteria; our bodies contain about ten times more bacteria cells than the cells that make up our body, a good proportion of these are in our gut, an astounding fact.

What are often called ‘good bacteria’ are various types of bacteria commonly found in our bowel, and it is felt that if this natural ecosystem is damaged by illness, then replacing those bacteria helps to reduce symptoms such as diarrhoea, bloating and pain, which often accompany some digestive diseases. The theory is that taking these bacteria in food or drink will replace the bacteria that are missing; however in reality the effects are variable.

These bacteria are produced from dairy foods, such as Lactobacillus, Bifidobacterium and Lactobacillus acidophilus – long names for such cool microorganisms. We have good evidence that taking bacteria at the start of a course of antibiotics can prevent the diarrhoea that can accompany these medicines – antibiotics can reduce the natural populations of good bacteria in our bowel, which slightly alters digestion of starchy foods, resulting in diarrhoea. The case for probiotic effectiveness in reducing episodes of ulcerative colitis is controversial, but probiotics can be effective in reducing occurrence of infections that occur in people who have had reconstructive small bowel surgery (called pouches,) and can prevent diarrhoea that occurs when travelling abroad. For illnesses such as food poisoning, they may reduce the amount of days you are ill and reduce the number of times you need to visit the loo -which is always a benefit!

The products that are available also have varying effects in people with irritable bowel syndrome (IBS,) and the evidence for their usefulness for preventing further attacks of crohns disease is still uncertain. As these products are generally not harmful in most individuals, if you have irritable bowel syndrome UK health professionals advise that you could try them and see if they work for you. If you have crohns disease or colitis, it is probably better to discuss this with your gastroenterologist before you try them out.  Try them for at least a month if you wish and follow the manufacturers instructions, you may need to continue taking them if you find them beneficial, as their effect can be temporary. It is also advisable to store these products as the manufacturer recommends and use them within the date advised, to ensure that the products are effective as they can be.

Some people may be better to avoid taking these bacteria, for example if you have a severe intolerance to lactose (a natural sugar found in dairy foods,) most of the manufacturers products are based on milk, therefore they may give symptoms, as they may contain varying amounts of lactose, depending on the product. However the bacteria will have reduced the amount of lactose naturally found in these foods, so caution is advisable if you wish to try them.  Also if your doctor has told you that you have a weak immune system then you should not take these products.

Again we do not have evidence that probiotics can be helpful in preventing allergies or stopping infections of the bladder in adults, so don’t waste your money! Although I was informed by blogger yesnobananas that there is some evidence for a strain of lactobacillus Ramnosus in protection from developing atopic eczema, which is hard to find, but see her blog for further information

http://yesnobananas.wordpress.com/2013/01/10/can-probiotics-prevent-food-allergy/

But where we know they are effective, or the products are recommended by your registered health professional, they are certainly worth considering. If you wish to try them and are not too sure about your situation, you could always discuss their use with your healthcare provider.

Health professionals can check the links below for evidence base references:

http://www.patient.co.uk/doctor/Probiotics-and-Prebiotics.htm

http://www.cochrane.org/search/site/probiotics