When I step into Professor Sanders office, the first thing I notice is the breathtaking view he has across Sheffield. I point this out to him and he laughs, “It is embarrassing but I often forget to look at it!”. This comes as no surprise, as a world expert in Coeliac Disease it is little wonder that Professor Sanders hasn’t had time to appreciate the view.
What got you into research into Coeliac Disease and gastroenterology in general?
Chance! If you work for good mentors it tends to make you want to be in their field or to work with them. I was very, very lucky that I had some very inspirational people around me and then everything just developed from there, I’m sure that I wouldn’t have done anything without their support.
Professor Sanders is being far too modest, Cofounding member of the Sheffield Institute for Gluten Related Illnesses two years ago, along with another prominent researcher from The Royal Hallamshire hospital in Sheffield (Professor Hadjivassiliou).
How have things changed since the establishment of the Sheffield Institute of Gluten Related Disorders?
That group has actually been around for a long time but we had never formalised our group if you wish. In terms of its research output we have published more than 100 papers on Coeliac Disease over a ten year period. We are, I think it would be fair to say, the premiere unit in the UK for this situation and are well recognised internationally.
So has our unit done even better with a new name? It’s difficult to say. I know that certainly we’re thriving, we have plenty of researchers… I think we’re doing fine thanks.
“Fine” might be a bit of an understatement if the long list of research projects you’re involved in is anything to go by! What current research are you working on?
I have a number of research areas Non Coeliac Gluten Sensitivity is one of them. That’s on going and that’s looking at really trying to work out who the individuals are who suffer with NCGS: what type of presenting symptoms can occur and if a gluten free diet will benefit them symptomatically.
Another area is looking at dietetic interventions in Coeliac Disease so right now we are running a group clinic study to see if group clinics are more effective than individual appointments. Hopefully, in due course, we will be running a dietetic intervention study looking at comparing whether you would prefer seeing a dietician rather than a gastroenterologist.
A third area is looking at point of care testing, something which we’re very keen on because there’s such a difficulty in making the diagnosis of Coeliac Disease. Often people wait for many years so point of care tests might shorten that time span.
And the fourth area is looking at trying to recognise changes when performing an endoscopy. The endoscopic work is on-going with a new scope called Magnaview, [utilising] new novel endoscopic techniques which have high magnification. This might allow us to see the villi directly and therefore see if they’re damaged or not.
With conducting research into endoscopes, would it be possible to create one which is less uncomfortable?
We’re the largest unit for something called Capsule Endoscopy in Europe, which is the pill camera that you swallow and takes pictures. Of course they don’t take biopsies but we are working in the area of remote endoscopy. In other words, the idea that you could have that pill camera and could steer it around your bowel and that maybe in time we’ll even be able to take biopsies. So really quite 21st century or sci-fi if you wish but who knows! Things are evolving.
Technology’s a wonderful thing! What’s new in terms of research into alternative treatments for Coeliac Disease?
There are a number of new therapies. AV003 is an enzyme which breaks up gluten to such an extent that you hope it will not be absorbed. Studies are on-going in North America and the United Kingdom, so we will have to wait and see what effect that will have on patients.
Another study which has only been at research level is looking at hookworms. Hookworms have been given to patients with Coeliac Disease and amazingly it switched off their immune system. If you imagine the world beginning, infections were a big problem for us. Some might say that conditions such a Coeliac Disease are self-immune diseases, which occur as a result of not having to fight off other infections in this sterile western world that we live in. For arguments sake you could say that by having hookworm you now have something far more serious to deal with but as fascinating a development as this is, whether that immunological response to hookworms can now be converted into a treatment still remains to be seen.
These treatments are obviously a long way off being readily available, for now, the only treatment for Coeliac Disease is a strict gluten free diet. An article published in “Gastrointestinal Endoscopy” revealed that for 30% of people diagnosed with Coeliac Disease on a gluten free diet might have persistent symptoms. Why is it that a gluten free diet doesn’t always work?
There are many reasons. The most common reason is an inadvertent exposure to gluten meaning there’s continued inflammation as a result. The first step for that 30% is for them to be reassessed by a dietician and to see if there’s maybe something slipped in there without them knowing.
The second reason might be that actually for some individuals their immune system might be supercharged, even the smallest amount of gluten which of course even gluten free products have a certain amount of gluten in them. For those super sensitive cases, we sometimes place them on a wheat free, gluten free diet, almost like a more stringent gluten free diet. Then finally it’s the possibility that you have another condition related. There are a number of associations between Coeliac Disease and other conditions which we may consider checking for: microscopic colitis, pancreatic insufficiency, bacterial overgrowth, lactose malabsorption, the list is endless. You have to work through these investigations to make sure that your patient doesn’t have those causes.
You mentioned Lactose malabsorption in there, why is it that some people develop a slight lactose intolerance after being diagnosed with Coeliac Disease?
Lactose is processed in the small bowel and we have an enzyme called lactase. In fact, biologically, from a mankind perspective, there’s quite a high prevalence of lactase enzyme deficiency. So quite a large number of us cannot process milk efficiently and if we’re given a certain quantity we develop symptoms. Now all of this is happening in the small bowel and you can imagine that if you have any disease that affects the small bowel then it can interfere with lactose because it’s all happening at the surface of the small bowel. So Coeliac Disease is a prime candidate for that, if you have Coeliac Disease and Villous atrophy or damage to your small bowel you will get a secondary lactose intolerance.
This might be a long question but from looking at several different websites and message boards on the internet there seems to be a lot of mixed advice about grain based spirits. Coeliac UK’s advice suggests that grain-based spirits are fine because all the gluten will be removed in the distillation process. Unfortunately from reading forums and message boards there are people, like myself, who feel very symptomatic after drinking an alcoholic drink made from grain-based spirits. From my research online there do not appear to be any people studies on this topic. Why are there no prominent people studies and why might grain-based spirits affect people differently?
I think you may well be right. First of all I think you are right that there are no people studies and secondly that you may still have symptoms and others might too. I guess everyone has assumed that gluten is the offending agent and in the distilling process you are somehow getting rid of gluten. But sometimes, with all things, you don’t know about the degree of contamination or whether your immune system recognises something which mimics gluten. I honestly don’t know, I don’t know if anyone else does.
I think it’d be quite an interesting thing to do a study on.
I find it quite astounding the effects that Coeliac Disease can have on the body.
Yeah, I think it’s a multisystem disease. You might argue that it enters through the gut and then travels to wherever it wishes, so it can give you something called a peripheral neuropathy where the nerves in your legs are damaged. You could present with an iron deficiency and other anaemias because you’re not absorbing things properly. I’m sure you’ve heard of a condition called dermatitis herpetiformis which is a skin condition; you present with a blistering skin rash but you have a flat bowel on biopsy.
In my mind what this tells us is gluten is the problem. It hits your small bowel, causes the damage that we’ve discussed and once it’s come through it produces all sorts of antibody responses. Depending on which one you get, you then perhaps present accordingly. Because there are different tissue transglutaminators and some might go to the brain, some might go to the skin; some might stay in the gut and just damage that. We don’t know yet, we’re working it out.
It’s quite frightening to think that Coeliac Disease can even affect the brain as is the case with Gluten Ataxia, could you tell me a bit more about that?
We are the international centre for this, my friend and colleague Professor Hadjivassiliou is the world expert. He has described that people may present with Ataxia, i.e. difficulty in terms of walking, with their gait, imbalance which is related to the back of the brain, an area called the cerebellum. This area is damaged and that actually for these patients if you put them on a gluten free diet and they have underlying Coeliac Disease or in some cases just a positive antibody then it will stop the deterioration of their neurological symptoms and in some cases it may even improve things.
What would you like to see more of in the future of gastroenterology and Coeliac Disease?
More funding for research but these things are not always straightforward.
I’d like to see far more dieticians dedicated to gastroenterology which is an area which has been hugely overlooked in terms of clinical practice and underfunded. I really feel that we need to champion the role of the dietician for gastrointestinal diseases, that’s absolutely imperative.
Why do you think that dieticians might have been overlooked in the past?
There are two reasons for this. One, the NHS funding is very much around Doctors. There is an assumption that all the allied Health Care professionals would be expanded accordingly but, of course, it never happened.
The second reason is that historically for gastrointestinal diseases, such as IBS, it has been considered that dietary therapies do not work particularly well. However, I think that things have changed hugely. There are large numbers of Coeliac patients who require dietetic advice which is the cornerstone of their management and there are now patients with functional gastrointestinal disease who would benefit from that too. So for me there should be a very reasonable number of dieticians dedicated to gastroenterology in every hospital in the United Kingdom.
Professor Sanders continues to practice medicine at the Royal Hallamshire hospital and is regarded as one of the leading international experts in Coeliac Disease. For more information about the Sheffield Institute of Gluten Related Illnesses please visit: https://www.sheffield.ac.uk/news/nr/gluten-related-diseases-1.259247