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SPRING 2018

ISSUE 3

Digestif NEWSLETTER

Good health begins with a balanced gut GP perspective on irritable bowel syndrome


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INSIDE THE ISSUE

Digestif Spring 2018 - Issue 3

The Digestif is the newsletter of The Primary Care Society for Gastroenterology. We welcome comments on the content as well as ideas for contributions to future issues. Letters for publication and suggestions for editorial contributions should be emailed to editor@pcsg.org.uk Main sponsor and advertising contact: Pauline Kent, of Satellite PR. Email: pauline@satellitepr.com Guidelines for writers are available on request. Editor (for Satellite PR): Jerry Budden Designer (for Satellite PR): Leah Watson Publisher: The Primary Care Society for Care Gastroenterology PCSG Secretariat, c/o Satellite PR 154-158 Shoreditch High Street, London, E1 6HU Tel: +44 (0) 20 3872 4903 Printer: Hollinger Print (Norwich)

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Is irritable bowel syndrome (IBS), a microbiome disease? Speakers’ Corner - IBD, a GP perspective

INTRODUCTION Rarely a day goes by without the microbiome hitting the headlines and for GPs faced with curious patients it’s hard to know how to handle the questions. The gut microbiota is a fascinating subject and the race is on to discover more. With around 100 trillion microbes in our guts (most being found in our colon) which outnumber our cells - discounting non-replicating red blood cells - by 10 to one, there’s a whole universe for us to get our heads around.

and many constituents of the Mediterranean diet are prebiotic - either with high levels of inulin like onions and garlic, or containing polyphenols like olive oil, nuts or red wine. I started taking Bimuno two months ago and I have to admit it’s doing something. I am sleeping better and generally feel well. In 2017, Michael Mosely reported similar findings in his ground-breaking BBC documentary The Truth About Sleep. At the start of his five-day experiment, Mosley spent 21% of his time in bed awake – by the end that had shrunk to 8%. Of all the strategies Mosley tested to treat his insomnia, he found prebiotics to be the most effective.

In this issue of the Digestif we’re looking at IBS and the microbiome with a fascinating article by Julie Thompson, who touches on the use of probiotic and prebiotic supplements and discusses the role of a FODMAP diet.

Placebo or reality? I am not sure. I am sure that our knowledge of the human microbiota is expanding rapidly and it may be possible to change the way we feel by doing something as simple as taking a prebiotic supplement. If I’ve whetted your appetite, then read on….

This newsletter is sponsored by Bimuno, a product I hadn’t heard of until recently. Bimuno is a prebiotic that feeds and increases the good bacteria in your gut. For the uninitiated, prebiotics act as fertilisers for gut microbes

DR MARION SLOAN

CONTRIBUTORS post bariatric surgery and gastrointestinal surgery diets. Julie’s clinic, Calm Gut, is based in Lancashire.

2. KEVIN BARRETT

1 Cover illustrator: Beverley Gene Coraldean, a UK-based freelance Illustrator. Untitled, is inspired by a futurist greenhouse and a flourishing microbiome.

This edition of the Digestif® has been sponsored by Bimuno. The editorial content has been developed by the PCSG, editors of The Digest and the contributors. Illustration: SantaLiza/Shutterstock.com

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1. JULIE THOMPSON Julie Thompson is a state registered specialist gastroenterology dietitian working in private practice and the NHS. She is also diet advisor to The IBS Network, the UK charity for people with irritable bowel syndrome. Julie’s specialty is dietary treatment of gut disorders such as irritable bowel syndrome, crohn’s disease, ulcerative colitis, coeliac disease, lactose & fructose malabsorption and complex food intolerances. She is also experienced in

Dr Kevin Barrett is Chair of the PCSG, a General Practitioner in Rickmansworth, Hertfordshire and Clinical Lead for Gastroenterology at the Hertfordshire Valleys Clinical Commissioning Group (HVCCG). His first house job was in gastroenterology, which piqued his interest in this area and it has continued to be an interest since he became a GP in 2002. Kevin has been involved in commissioning since 2008 and has been the clinical lead for gastroenterology for HVCCG for the last eighteen months and has worked closely with the local gastroenterologists to develop & distribute pathways for faecal calprotectin testing and the diagnosis and management of IBD. In addition he is the RCGP and Crohn’s and Colitis UK Inflammatory Bowel Disease Clinical Champion.

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FEATURE

JULIE THOMPSON

E L E M O W I O B B O R E L C I B M A T A I IS IRR , ) S B I ( E M O R D DISEASE? N Y S Gut health is currently a favourite topic with the public, and we are learning much more about our microbiome, through initiatives such as the human microbiome project. Irritable bowel syndrome (IBS) is a prevalent chronic condition affecting the bowel with symptoms of abdominal pain, constipation, diarrhoea or a mixture of both. There is no cure, but treatment developments are continuing at a pace. The microbiome is affected in IBS but also offers exciting treatment prospects. It has been known for some time that patients with IBS have an altered microbiome, and with some patients diagnosed with IBS post gastroenteritis, it is entirely reasonable to think that dysbiosis is a significant factor in the pathogenesis of IBS. Patients with IBS have reduced numbers of populations of lactobacillus and bifidobacteria, in both diversity of the populations and numbers. Alterations in the diet and medications are another possible cause of dysbiosis in IBS, plus differences occur in ratios of aerobes to anaerobes. Therefore, the idea that all cases of IBS at diagnosis are merely a consequence of mental ill health is no longer tenable. Previous acute GI inflammation is a significant risk factor for the development of post-infectious IBS. Also, evidence has emerged in support of microscopic inflammation as a primary factor in the pathophysiology of IBS, without necessarily a clinical history of infection, plus alteration of the intestinal immune system of the large bowel1. Commensal bacteria are found in the gut lumen and in the mucus layer lining the enterocytes, where they can influence immune function and protect the host from pathogens. Interestingly sterile animal models have been found to have abnormal peristaltic function and bile acid metabolism; suggesting that the enigmatic commensal microbiota that live with us have a role in keeping the bowel function regular.

Treatment with probiotics Probiotics are live microorganisms that provide health benefits when given in the correct dose, although the European Food Standards Agency has yet to confer use of this definition in product marketing. A systematic review and meta-analysis has shown that probiotics are overall effective in IBS2. However, which strains, doses and products are most beneficial is less clearcut3. With a heterogeneous condition such as IBS and a treatment that could be considered a functional food, varying by number and type of species, the dose of microbe and form (drink, tablet or yoghurt), perhaps this is unsurprising. Industry funds probiotic research, repeat studies to strengthen the evidence-base for a specific product are expensive and unlikely to be replicated. Probiotics are not harmful to most, and patients like the concept of probiotic treatment, treatment also chimes with the public’s interest in ‘gut health’. However, cost needs consideration and the patient informed that they might not help all their symptoms. UK IBS and diet guidelines4 do recommend their use as a first-line treatment for IBS if patients wish to try them.

Gut microbiota profiling in IBS Business is quick to enter a new and growing field, and some companies are offering gut microbiota profiling tests to the public. However, it is too early in the research into the microbiome and IBS for using definitive testing, such as this. Patients have attended my clinic, test results in hand,

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with great anticipation of some discussion around the results. Unfortunately, we currently do not have enough evidence of the implications of these individual profiles for gut ill health; also, individual populations are likely to vary. We have little evidence in what targeted treatment would modify a specific profile, although this idea is indeed a possibility for future consideration.

Prebiotics Prebiotics are food for the microbiota and have great potential for improving the gut microbiota population; however prebiotic use often results in symptoms for patients with IBS. We have insufficient evidence of the effects of prebiotics for IBS treatment. Only one product has been effective so far, a trans-galactooligosaccharide (B-GOS), research showed at a lower level of supplementation this prebiotic proved clinically beneficial in IBS – the higher dose, while resulting in the best prebiotic effect, was less effective clinically5. Study numbers were small, but B-GOS proves to be a prebiotic worthy of further study.

Faecal microbiota transplantation (FMT) A background of a 90% effectiveness of FMT for C. difficile infections has led to considerable interest in FMT treatments for IBS. The research was limited to case studies and case series until a systematic review was published in 20176. This study was conducted in patients with IBS-D and IBS-M and gave a positive response for 65% of participants at three months, with no severe events, but not at 12 months. With emerging knowledge on the effects of the microbiota on health much more evidence is needed before considering this treatment and perhaps donor choice needs to be approached with care and rigorous screening. Whether patients would be willing to try this treatment using other people’s faeces is yet to be discovered, but IBS patients are undoubtedly tenacious in their approach to trying new developments.


CASE STUDY

Antibiotics Non-absorbable antibiotics have been studied in IBS and have some evidence of short-term effectiveness7. This systematic review gave improvements in global symptoms and bloating. The treatment is theorised to change gut motility and alter host immune response in those with IBS-D and IBS-M. For IBS-C preliminary research has suggested slowing of gut motility is related to methanogens8 (methane-producing microbes) Methaninobrevibacter smithii and Methanospaera stadmagnae. The methane these microbes produce has been shown to reduce gut motility, and the study states preliminary treatment efficacy with antibiotics.

Treatment with diet Diet is one treatment area for IBS in which patients show interest, and the low fodmap diet has been a popular and effective treatment. The diet reduces the fermentation that drives symptoms of IBS. It reduces fermentable oligosaccharides, disaccharides, monosaccharides and polyols. These carbohydrates travel through the gut, causing osmotic issues, plus fermentation by gut microbes results in bloating, wind, constipation and or diarrhoea and abdominal pain via visceral hypersensitivity. The diet has three stages - a reduction of fodmaps, to achieve a baseline level of symptoms, re-introduction - to test which foods are problematic; then the patient moves onto a modified diet introducing some tolerated foods back into their diet. The diet is effective for patients with the help of a dietitian – all patients should be referred9. However, there is a price to pay – this diet reduces the variety and number of bacteria in the large bowel10 as many high fodmap foods are prebiotic. We don’t know the implications for the long-term gut health of the diet yet. Re-introduction of high fodmap foods to tolerance is therefore vital.

Stool volatile organic compounds Recent preliminary research has suggested that people who benefit from a low fodmap diet may have a microbiome, which produces a combination of volatile organic compounds that can be used to predict diet efficacy with a 97% accuracy. A test is currently under development for future use in clinics11. This fascinating research might result in better targeted dietary treatment for IBS.

Conclusion It is an exciting time for treatment development for IBS, and the microbiome offers an exciting future specialism. Dysbiosis is a factor in the pathogenesis of IBS and the microbiota will continue to provide insight and treatment opportunity the more we learn about the gut microbiota.

Mrs Smith has a diagnosis of IBS after a bout of traveller’s diarrhoea, and she has had symptoms of diarrhoea, bloating and abdominal pain for some time. She is a frequent attendee at the surgery and has tried some first line advice for IBS and diet. Reduction of caffeine intake and stopping consumption of carbonated drinks did give some symptom resolution, but it has not entirely resolved her symptoms to her satisfaction. First line advice for IBS is useful for some patients, and this can reduce the overall fodmap load to the bowel depending on what advice is given*, Mrs Smith is systematically trying this advice. She attends the surgery after being seen by someone at a health fair who advised that it would be useful to have her gut microbiota profile tested, the therapist said that ‘the bad bacteria in her gut are the cause of her IBS’. She has brought her microbiota profile test results to discuss. ‘Doctor, here are my results – the therapist has said that my levels of lactobacillus something is low (she points to a Lactobacillus strain), and this one is a bad one (she points to a bifidobacteria strain) - can you recommend a probiotic to help?’ ‘Well, Mrs Smith, these results are fascinating, but currently, we don’t have enough information to be able to use these results specifically’… ‘ the bad bacteria you mention is normally found in your bowel and is not harmful, however, if you have a wish to try a probiotic we could see which ones are useful for IBS’… ‘these products may not resolve all your IBS symptoms but are worth trying.’ ‘What about prebiotics? The therapist mentioned those too.’ ‘Prebiotics are indeed food for the microbes in your gut and can change the types. Unfortunately, they can also make people’s symptoms worse, if we don’t know whether you have intolerances to fructans sugars contained in prebiotics. What we could do perhaps is refer you to a dietitian to find out what FODMAPs you can tolerate and then we could try prebiotics if you wish, if you don’t have a problem with them.’ The Doctor refers the patient to a dietitian. ‘While you are waiting for the appointment it might be useful to try a probiotic’ The doctor advises three different probiotic products for Mrs Smith to try. “Use one of these products at a time, take it for a month, as the manufacturer advises, and see if it helps. If it helps you should continue to take it, if not you could try another. Do let me know how you get on…” *A downloadable first line diet sheet is available from www.bda.uk.com/foodfacts (This case study is not based on a true patient case)

References 1. Ohman L, Simren M. (2010) Pathogenesis of IBS: role of inflammation, immunity and neuroimmune interactions. Nat Rev Gastroenterol Hepatol. 2010;7:163–73. 2. Ford AC, Quigley EMM, Lacy BE, Lembo AJ, Saito YA, Schiller LR, et al. Efficacy of prebiotics, probiotics, and synbiotics in irritable bowel syndrome and chronic idiopathic constipation: systematic 302 Adv Ther (2018) 35:289–310 review and meta-analysis. Am J Gastroenterol. 2014;109:1547–61 3. McKenzie Y.A., Thompson J., Gulia P. & Lomer M.C.E. (2016) British Dietetic Association systematic review of systematic reviews and evidence-based practice guidelines for the use of probiotics in the management of irritable bowel syndrome in adults (2016 update). J Hum Nutr Diet. DOI: 0.1111/jhn.12386 4. McKenzie Y.A., Bowyer R.K., Leach H., Gulia P., Horobin J., O’Sullivan N.A., Pettitt C et al (2016) British Dietetic Association systematic review and evidence-based practice guidelines for the dietary management of irritable bowel syndrome in adults (2016 update). J Hum Nutr Diet. DOI: 10.1111/jhn.12385 5. Silk DBA, Davis A, Vulevic J, Tzortzis G, Gibson GR. (2009) the effects of a trans-galactooligosaccharide prebiotic on faecal microbiota and symptoms in irritable bowel syndrome. Aliment Pharmacol Ther. 2009;29:508–18. 6. Johnsen PH, Hilpusch F, Cavanagh JP, Leikanger IS, Kolstad C, Valle PC, et al. (2017) Faecal microbiota transplantation versus placebo for moderate-to-severe irritable bowel syndrome: a double-blind, randomised, placebo-controlled, parallel-group, single centre trial. Lancet Gastroenterol Hepatol. 2017;3(1):17–24. 7. Menees SB, Maneerattannaporn M, Kim HM, Chey WD (2012). The efficacy and safety of rifaximin for the irritable bowel syndrome: a systematic review and meta-analysis. Am J Gastroenterol. 2012;107:28–35 8. Konstantinos Triantafyllou, Christopher Chang and Mark Pimentel (2012) Methanogens, Methane and Gastrointestinal Motility J Neurogastroenterol Motil, Vol. 20 No. 1 pISSN: 20930879 eISSN: 2093-0887 9. National Institute for Health & Care Excellence (2016) QS114 Quality Standards for IBS London: NICE 10. Staudacher HM, Lomer MC, Anderson JL, Barrett JS, Muir JG, Irving PM et al (2012) Fermentable carbohydrate restriction reduces luminal bifidobacteria and gastrointestinal symptoms in patients with irritable bowel syndrome. J Nutr. 2012 Aug;142(8):1510-8. DOI: 10.3945/jn.112 1. 11. Rossi M, Aggio R, Staudacher HM, Lomer MC, Lindsay JO, Irving P, Probert C, Whelan K. (2018) Volatile Organic Compounds in Faeces Associate With Response to Dietary Intervention in Patients With Irritable Bowel Syndrome. Clin Gastroenterol Hepatol. Mar;16(3):385-391.e1. doi: 10.1016/j.cgh.2017.09.055. Illustrations: Alena Ohneva/Shutterstock.com. Photo: Elenadesign/Shutterstock.com

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SPEAKERS’ C

ORNER

KEVIN BARRETT

A GP’S PERSPECTIVE ON THE DIAGNOSIS AND MANAGEMENT OF IRRITABLE BOWEL SYNDROME Prevalence & impact

Diagnosis

Irritable bowel syndrome (IBS) is a condition that GPs see every day. It affects 10-20% of the UK population, is more common in women than men with a 3:2 ratio, and particularly affects those aged 20-30. The symptoms can have a significant impact on those in education and work and can be distressing. Repeated visits with failure of treatments can be frustrating for both patient and GP.

The diagnosis of IBS can be difficult as the symptoms overlap with many other conditions including colorectal carcinoma, IBD, ovarian carcinoma, endometriosis and coeliac disease. The National Institute for Health and Care Excellence (NICE) positive diagnostic criteria for IBS (NICE CG61) include a persistent (greater than six month) history of change in bowel habit or bloating or abdominal pain with the presence of at least two other symptoms (Table 1). In order to diagnose IBS one must exclude organic pathology, particularly colorectal cancer in patients presenting over the age of 40 (Table 2) and ovarian cancer, particularly in women over the age of 50 (Table 3). A good history is essential, and an abdominal examination to exclude hepatomegaly, ascites, and abdominal masses should be carried out. If appropriate, a rectal examination may reveal a pelvic mass or rectal carcinoma. Diagnostic tests should be kept to a minimum. It is appropriate to give a patient a diagnosis of IBS if blood tests exclude inflammation, anaemia, coeliac disease, thyroid dysfunction and ovarian carcinoma, and a faecal calprotectin is normal. However, the diagnosis should always be reconsidered in patients not responding to treatment, or those whose pattern of symptoms change or when red-flag symptoms occur.

Symptoms IBS is an illness that has no specific cause, no distinctive pathology and no single effective treatment. Irritable bowel syndrome (IBS) is a chronic, relapsing and often life-long disorder. It is characterised by the presence of abdominal pain or discomfort, which may be associated with defaecation and/or accompanied by a change in bowel habit. There is an equal split into three heterogenous groups: those with symptoms where diarrhoea is predominant (IBS-D), those where constipation is predominant (IBS-C) and those with mixed diarrhoea and constipation (IBS-M). There is significant variability in prevalence worldwide.

Visceral pain receptor responses are different, and there are differences in the gut microbiome of patients with IBS compared to those with Inflammatory Bowel Disease A clear organic cause has yet to be found, and it is classified as a functional bowel disorder, but research is demonstrating that there may be detectable differences in patients with IBD who have an exaggerated gastrocolic reflex, more rapid gastric emptying, increased small bowel contractions, and increased small intestinal transit. Visceral pain receptor responses are different, and there are differences in the gut microbiome of patients with IBS compared to those with Inflammatory Bowel Disease (IBD)1. Volatile organic chemicals in the breath of patients with IBS have been shown to differ from patients with IBD2 but a clear diagnostic tool is not yet available.

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Management The management of IBS has three components: a psychological approach, diet and lifestyle modification, and medication. To help patient manage their symptoms a good explanation of the pathophysiology is needed. Charities such as www.theibsnetwork.org and www.corecharity.org.uk can provide invaluable advice. From April 2018 all Clinical Commissioning Groups in England are required to offer IAPT services, and many patients find this to be very helpful. Lifestyle modification is the second treatment arm. Adjusting the amount of fibre in the diet, keeping a food diary so that “trigger foods” can be identified, and the use of probiotics and prebiotics are all strategies that should be attempted. The low-FODMAP diet can be effective but involving a dietician may be required. Exercise can be beneficial, either low-impact aerobic activity or core-strengthening exercise such as yoga, pilates or tai chi. Some patients respond very well to acupuncture. Antispasmodic, laxative or anti-motility medications all have a part to play.


Table 1: NICE CG61 positive diagnostic criteria for IBS Patients must give at least a six-month history of either:

• Abdominal pain or discomfort. • Bloating. • Change in bowel habit.

Consider positively diagnosing IBS only if abdominal pain is either relieved by defecation, or associated with altered bowel frequency or stool form; AND at least 2 of the following are present:

• Altered passage of stool (straining, urgency, incomplete evacuation). • Abdominal bloating (women >men), distention tension or hardness. • Symptoms aggravated by eating. • Passage of mucus rectally.

Lethargy, nausea, backache and bladder symptoms may be used to support diagnosis.

Table 2: NICE NG12 1.3 Lower gastrointestinal tract cancers: colorectal carcinoma 1.3.1 Refer adults using a suspected cancer pathway referral (for an appointment within 2 weeks) for colorectal cancer if:

Adjusting the amount of fibre in the diet, keeping a food diary so that “trigger foods” can be identified, and the use of probiotics and prebiotics are all strategies that should be attempted. Lactulose should be avoided. Tri-cyclic medication or SSRIs can be effective, and explanation of the disordered gut nervous system in IBS can help patients understand their mechanism of action and improve compliance.

• they are aged 40 and over with unexplained weight loss and abdominal pain or • they are aged 50 and over with unexplained rectal bleeding or • they are aged 60 and over with: o iron-deficiency anaemia or o changes in their bowel habit, or • tests show occult blood in their faeces.

1.3.2 Consider a suspected cancer pathway referral (for an appointment within 2 weeks) for colorectal cancer in adults with a rectal or abdominal mass.

1.3.3 Consider a suspected cancer pathway referral (for an appointment within 2 weeks)

for colorectal cancer in adults aged under 50 with rectal bleeding and any of the following unexplained symptoms or findings:

Summary IBS is a condition that affects a large number of patients seen in primary care. A confident diagnosis can be made in the majority of cases, but one needs to be mindful of the patient who does not respond to treatment or in whom the pattern of symptoms changes. IBS can coexist with many other gastrointestinal conditions and patients often complain that they were “misdiagnosed” with IBS for many years before organic pathology was detected. There is no one-size-fits-all approach to the management of IBS, but dietary modification, psychological support and medication all have key parts to play. References 1. Distrutti, E. M. (2016). Gut microbiota role in irritable bowel syndrome: New therapeutic strategies. World Journal of Gastroenterology, 22(7), 2219–2241. 2. Probert, C. R. (2014). Fecal volatile organic compounds: a novel, cheaper method of diagnosing inflammatory bowel disease? Expert Review of Clinical Immunology, 10:9, 1129-1131.

• abdominal pain • change in bowel habit • weight loss • iron-deficiency anaemia.

Table 3: NICE NG12 1.5 gynaecological cancers: ovarian cancer 1.5.1 Refer the woman urgently if physical examination identifies ascites and/or a pelvic or abdominal mass (which is not obviously uterine fibroids).

1.5.2 Carry out tests in primary care if a woman (especially if 50 or over) reports having

any of the following symptoms on a persistent or frequent basis – particularly more than 12 times per month:

• persistent abdominal distension (women often refer to this as ‘bloating’) • feeling full (early satiety) and/or loss of appetite • pelvic or abdominal pain • increased urinary urgency and/or frequency.

1.5.3 Consider carrying out tests in primary care if a woman reports unexplained weight loss, fatigue or changes in bowel habit.

1.5.4 Advise any woman who is not suspected of having ovarian cancer to return to her GP if her symptoms become more frequent and/or persistent.

1.5.5 Carry out appropriate tests for ovarian cancer in any woman of 50 or over who has experienced symptoms within the last 12 months that suggest irritable bowel syndrome (IBS), because IBS rarely presents for the first time in women of this age.

Illustration: Bardocz Peter/Shutterstock.com

Information from NICE reproduced under the NICE UK open content license.

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COMING SOON Vol 6. Issue 11

2018 - No 2

TheDigest VOICE OF PRIMARY CARE GASTROENTEROLOGY

Can a low carb approach to NAFLD work? The role of Real World Evidence in treating functional GI disorders

What might you have missed?

All avaliable online www.pcsg.org.uk/ the-digest/

Digestif Issue 3  

The Digestif is the newsletter of The Primary Care Society for Gastroenterology.

Digestif Issue 3  

The Digestif is the newsletter of The Primary Care Society for Gastroenterology.