Towards dietary assessment and interventions for patients with Inflammatory Bowel Disease
Peters, Vera
DOI:
10.33612/diss.159023461
IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from
it. Please check the document version below.
Document Version
Publisher's PDF, also known as Version of record
Publication date:
2021
Link to publication in University of Groningen/UMCG research database
Citation for published version (APA):
Peters, V. (2021). Towards dietary assessment and interventions for patients with Inflammatory Bowel
Disease. University of Groningen. https://doi.org/10.33612/diss.159023461
Copyright
Other than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).
Take-down policy
If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim.
Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons the number of authors shown on this cover page is limited to 10 maximum.
1
CHAPTER 1
GENERAL INTRODUCTION
Inflammatory Bowel Disease (IBD) comprises mainly Crohn’s Disease (CD) and Ulcerative Colitis (UC), which are chronic inflammatory disorders that have a tedious and incapacitating nature.1,2 It impairs quality of life of patients and raises healthcare costs for society.3 More than 1 million residents of the USA and over 2.5 million in Europe are estimated to be affected by IBD; the incidence is rising in non-Western countries too.3,4 Prevalent symptoms include abdominal pain, (bloody) diarrhea, rectal bleeding and/or rectal urgency (UC only), weight loss and fatigue.1,2 Albeit IBD is a disorder of the gastro-intestinal tract, extra-intestinal manifestations can present in almost every organ, being the eyes (4%), skin (10%), joints and bones (arthropathy: 15%, arthritis: 7%, osteopenia/osteoporosis (20%)), vasculature (thromboembolic event (4%)), kidneys, liver and biliary tract.5,6 Furthermore, IBD has an erratic course and disease behavior varies within patients and between patients.1,2 Moreover, periods of severe sickness are alternated with periods of remission.1,2
The exact etiology of IBD is unknown. However, it is expected that IBD is set in motion by environmental and lifestyle factors such as an infection, smoking or a diet. Other important factors include a genetic predisposition, an aberrant mucosal immune response and a dysbiosis in the gut.7 Individual risk factors might not be potent enough to cause disease. However, when factors accumulate and interactions between risk factors occur, it leads to the development of IBD or triggers disease flares, Figure 1. This interplay of pathophysiological factors turns IBD into a multifactorial disease.8 Furthermore, IBD shares several underlying inflammatory pathways with apparently phenotypically unrelated disorders. Consequently, IBD can be classified as an Immune-Mediated Inflammatory Disease (IMID).9 Examples of those disorders include hidradenitis suppurativa, psoriasis, ankylosing spondylitis/ seronegative arthropathies, type 1 diabetes and multiple sclerosis.
Figure 1. Pathophysiological factors are expected to play a role in triggering and maintaining IBD, a multifactorial
1
The prevalence of IBD is high in Western societies3 where a typical Western diet is often consumed; characterized by high intake of fat and sugar along with low intake of vegetables and fruits. Subsequently, this Western diet is often reported as a predisposing factor in the development of IBD.10 Evidence for the role of nutrition in IBD can be found in children with CD who receive exclusive enteral nutrition (EEN) as their primary induction therapy. EEN has been proven to be equally effective in inducing clinical remission when compared to steroid treatment. Since steroids have adverse effects in children including reducing their growth, EEN is preferred to steroids for induction treatment in children.11,12 Remarkably, in adults, tube feeding is often reserved for severely ill patients since adherence is generally low. Recently, a dietary treatment (partial enteral nutrition in combination with a Crohn’s Disease Exclusion Diet13) was proven to be a useful strategy in patients who failed biological treatment. Furthermore, specific carbohydrate diets,14–16 a semi-vegetarian diet,17 and an anti-inflammatory diet18 seem to be beneficial too. In addition, several food items are considered to be potential risk factors (fat, sodium19, red and processed meat10,20) or protective factors (fiber, fruit, vegetables, fish oil and nuts20) for the development and progression of IBD.
Despite ongoing efforts,21,22 evidence-based dietary guidelines for clinical practice are lacking. Hence, physicians find no reliable answer to the question of patients: “What should I eat?”.23 Noteworthy, 60% of patients indicated diet to be either more or equally important compared to their drug therapy.24 Subsequently, 69% of patients reported that they modify their diet to alleviate disease symptoms.25 However, patients’ dietary knowledge is often based on personal experiences (81%)24 rather than being properly regulated by a physician or dietician. Unsupervised dietary modifications create a risk for overly restrictive diets26 and nutrient deficiencies24,27 which potentially cause an unintentional deterioration of disease course. Obviously, nutritional change is often a complementary therapeutic strategy for IBD patients whereas habitual intake is relatively simple to adapt. Why is it then, that in practice no dietary advice is given on a daily basis? The problem lays in the complexity of nutritional research. First, due to the variety and complexity of the diet exposure itself. A diet consists of multiple food items consumed in a variety of concentrations (portion sizes), preparations (i.e. baking, cooking, grilling, steaming, etc.), combinations (dishes containing multiple products) and at different time points (breakfast, lunch, diner, snack time, etc.). On top of that, all food items consist of multiple nutrients which can be classified as macronutrients, micronutrients and trace elements. Moreover, food items also contain emulsifiers and food additives. Each food item has a unique constitution which has been described for a subset of food items in the Dutch Food Composition Table (NEVO Table).28 All constituents have potential short- and long-term individual effects on the body plus additional effects when interacting with other components of the diet. Furthermore, constituents of the diet are being metabolized in the body, potentially creating new metabolites that might have an effect on the body too. To summarize, diet is a large exposure which changes over time and in its constituents, making it challenging to study diet in a constructive way.
Secondly, nutritional research is complex due to the interaction of multiple pathophysiological factors. As mentioned before, IBD is a multifactorial disorder, meaning that other factors
besides diet (i.e. environment, lifestyle, microbiome, immune response, genetics) play a role in the etiology and pathophysiology of those diseases. Due to a variation in those pathophysiological factors, foods potentially have different interactions in individuals. For example, the microbiome is thought to be influenced by the food one takes in and vice versa how food is being digested is thought to be influenced by the microbiome. Differences in microbiome diversity are established in IBD (unknown whether it is cause or response) and are associated with certain food items. For example, Bolte et al.29 found that a plant-based diet was associated with increased abundances of short chain fatty acid (SCFA) producing bacteria and fermentation pathways. Furthermore, they showed that a pattern characterized by intake of plant protein, vegetables, fruits, cereals, nuts, wine and fish was associated with increased abundance of Roseburia hominis, Fecalibacterium prausnitzii and Bifidobacteria and carbohydrate fermenting pathways. These varieties in microbiota abundance between individuals might attribute to a different interaction with foods. On top of the fact that diet as an exposure is already large and continually changing (first reason), these additional varieties due to the interaction between pathophysiological factors are creating more heterogeneity in disease course, which makes it complex to study the effect of nutrition.
Thirdly, nutritional research is complex due to measuring difficulties and bias. Diet changes over time and in its constituents, therefore it is difficult to develop proper assessment tools capturing it. Currently, two types of assessment tools can be distinguished: tools measuring short-term (intake on a given day) or long-term (usual intake, i.e., long-run daily average) dietary intake. The short-term tools can be divided into 24-hour recalls and food records, and the long-term tools into food frequency questionnaires (FFQs) and screeners.30 Each tool has its own strengths and pitfalls.30 When assessing diet, you always rely on the memory of participants (except when using a food record) what makes these tools subjective to recall bias. Furthermore, reactivity can occur which is a change in behavior due to participants being made aware that their dietary intake is or will be assessed. This is called the Hawthorne effect. Several steps need to be taken to achieve evidence-based dietary guidelines for clinical practice. Hence, it should be considered how to address the abovementioned issues; the complexity of diet as a large and continually changing exposure, the interaction of diet with other pathophysiological factors and the fact that dietary assessment tools are constrained. One of the steps that needs to be taken is to further clarify the role of nutrition as
pathophysiological factor in IBD (Part I). IBD is thought to be triggered and maintained
by an interplay of multiple pathophysiological factors (i.e. genetics, immune dysregulation, gut dysbiosis, environmental factors, etc.). Let’s reverse this hypothetical model and “tip the IBD scale to the good side”; the role that these factors play in the pathophysiology should be converted in order to be deployed in therapy or in future prevention of these diseases. For example, if it is discovered what dietary elements (e.g. nutrients, food items, diets) have a negative effect, patients can eliminate those or at least reduce their intake as a form of complementary therapy. Furthermore, if one is able to clarify what dietary elements have a positive effect, patients can optimize those effects by increasing their intake. Currently, many patients fail drug therapy and in long-term therapy with biologicals loss of response (up to
1
40%) is a significant issue.31 If you place this in the context of the model; drug therapy alone might not be sufficient to induce remission when the other pathophysiological factors are not optimized. It should be mentioned that some factors, for example genetics, cannot be modified and create a (minimal) susceptibility to developing diseases or flares. However, refining modifiable factors such as diet could potentially empower drug therapy. This model takes diet into account as a fluctuating exposure which has interactions with other factors. Having that said, managing dietary intake and other risk factors become an essential element of this model.
Another step that needs to be taken is to optimize dietary assessment tools and adapt those tools to the population that is being researched (Part II). Take the FFQ, this tool usually is self-administered and takes about 30-60 minutes to fill out (on paper or digital). An FFQ adequately captures past long-term diet32 and collects data on frequencies of a selected number of specific foods and beverages during a specified period of time (week, month or year). Limitations are that detailed product information is lacking (e.g. brand) and that it is based on a predefined list of food items. Nevertheless, an FFQ is often the method of choice in large cohort studies because it is cheap and easy to administer.32 This tool is normally developed for the general population. IBD patients experiment with their food intake to alleviate symptoms, they avoid certain food items and take in alternative products instead.33 Whereas an FFQ is designed for the general population, it does not incorporate those alternative food items and thus neglects an important part of the habitual intake of IBD patients. Such facts should be taken into account when developing new tools including an IBD-specific FFQ.
Another suggested step includes providing high-quality evidence (Part III). The hierarchy of evidence pyramid34 shows that randomized controlled trials (RCTs) and systematic reviews and meta-analyses of RCTs are providing the highest-quality evidence. At present, high-quality studies in the field of nutrition, especially RCTs, are sparse. The lower high-quality studies often deliver the evidence that is needed as input for an RCT. Nevertheless, not every element of the diet can be proven to be effective in such studies before one can start conducting RCTs. As mentioned before, nutrition is a large and continually changing exposure and hence researching every element into detail before conducting RCTs is unwanted if we want to provide patients with dietary advice in the near future. Thus, the best-available evidence should be appraised and serve as input for dietary trials. Moreover, knowledge gaps should be identified and filled by qualitative research.
If the proposed steps are taken, one is on the right path to enable development of evidence-based dietary guidelines for IBD. Hence, the overall aim of this thesis is to contribute to the field by taking steps to further elucidate the role of nutrition in the pathophysiology of IBD, developing a new nutritional assessment tool and provide high-quality evidence.
THESIS OUTLINE
In Chapter 1, a general introduction into the topic “Towards dietary assessment and interventions for patients with Inflammatory Bowel Disease.” is given.
PART I – PATHOPHYSIOLOGICAL FACTORS
The first part of this thesis will focus on further clarifying the role nutrition plays in the pathophysiology of IBD. Since it is possible to modify diet, a role for dietary modifications is often proposed as complementary therapy for IBD.35 It is known that IBD patients often modify dietary habits to alleviate their disease symptoms.33 However, when unsupervised, these dietary habits can lead to overly restrictive diets and potential nutritional deficiencies. To better support patients in their nutritional journey to symptom relieve, first it should be identified whether parts of the diet are sub optimal in the context of disease or flare development. Therefore, studying the differences between and within patients and controls is necessary. In Chapter 2, it is hypothesized that patients have different dietary habits compared to controls. This was then studied by comparing the habitual dietary intake of IBD patients to population-based controls of the LifeLines DEEP cohort.
Chapter 3 focuses on specific dietary patterns which might form a risk in developing IBD. To
study this topic, dietary patterns were examined in the LifeLines cohort. These were evaluated by observing dietary patterns and linking these to developing UC or CD during a maximum follow-up period of 11 years.
To further deepen the knowledge of dietary habits of IBD patients, the differences in dietary intake between patient populations and within patients were studied. It was hypothesized that the differences in culture in two geographically distinct provinces in the Netherlands might influence the dietary intake of IBD patients. Furthermore, it was considered whether or not certain dietary patterns play a role in triggering disease flares. Hence, in Chapter 4, the dietary intake of IBD patients from Maastricht (South Limburg IBD cohort) and Groningen (1000IBD cohort) were compared. Moreover, it was evaluated if a certain dietary pattern increases the risk on flare occurrence. A two-year follow-up period of time was used in this study.
PART II – DIETARY ASSESSMENT TOOLS
In the second part of this thesis, the focus will be on the development of a new dietary assessment tool; the Groningen IBD specific Nutritional Questionnaires (GINQ). As described in the introduction, new tools are needed to better record the dietary intake of patients to get more reliable data to study the pathophysiology of IBD. Since IBD patients often experiment with their food intake, their intake differs from the general population for whom these tools are normally designed. Therefore, there is a need for a tool that properly assesses those dietary modifications as well. In Chapter 5, a new dietary intake tool (GINQ-FFQ) is introduced which aims to contribute to better assessment of dietary intake of this specific population.
1
PART III – HIGH-QUALITY EVIDENCE
The last part of this thesis will focus on high-quality evidence, meaning a systematic review and the set-up of a randomized placebo-controlled trial.
There are conflicting practice-based dietary recommendations given to IBD patients about the intake of dietary fiber. No specific quantity for types of dietary fibers is recommended by European countries. The goal of Chapter 6 is to establish if all types of dietary fiber have the same effect on IBD. Hence, the effect of intake of specific fibers in IBD patients which are reported in RCTs were assessed and are discussed in this systematic review. The available literature, studying types of fibers, was also graded on the risk of bias using the Cochrane Collaboration Risk of Bias Tool (RoB 2.0).36
More high-quality studies are needed to improve the body of currently available evidence. As mentioned in the introduction, one cannot wait to conduct RCTs until all elements of the diet are proven in other study set-ups to play a role in the pathophysiology of IBD. Therefore, the best-available evidence is used as input to develop the Groningen anti-inflammatory diet (GrAID) which will be assessed in an RCT. In Chapter 7, the study set-up is described. This randomized placebo-controlled trial aims to evaluate the effect of a three-month anti-inflammatory diet (GrAID) or a colon-delivered vitamin B2, B3, C supplement (ColoVit) compared to a placebo on the disease course of CD and microbiome parameters in patients and healthy controls. In this study, IBD will function as a model for other IMIDs in which the GrAID and ColoVit can potentially play a role too.
In Chapter 8, the main findings of these thesis will be summarized, and future perspectives will be discussed.
REFERENCES
1. Stange, E. F. et al. European evidence-based Consensus on the diagnosis and management of ulcerative colitis: Definitions and diagnosis. J.
Crohn’s Colitis 2, 1–23 (2008).
2. Van Assche, G. et al. The second European evidence-based Consensus on the diagnosis and management of Crohn’s disease: Definitions and diagnosis. J. Crohn’s Colitis 4, 7–27 (2010). 3. Kaplan, G. G. The global burden of IBD: from 2015 to 2025. Nat. Rev. Gastroenterol. Hepatol. 12, 720–727 (2015).
4. Molodecky, N. A. et al. Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review.
Gastroenterology 142, 46–54 (2012).
5. Spekhorst, L. M. et al. Cohort profile: Design and first results of the Dutch IBD Biobank: A prospective, nationwide biobank of patients with inflammatory bowel disease. BMJ Open 7, e016695 (2017).
6. Danese, S. et al. Extraintestinal manifestations in inflammatory bowel disease.
World J. Gastroenterol. 11, 7227–36 (2005).
7. Ananthakrishnan, A. N. et al. Environmental triggers in IBD: A review of progress and evidence.
Nature Reviews Gastroenterology and Hepatology 15,
39–49 (2018).
8. Ananthakrishnan, A. N. Epidemiology and risk factors for IBD. Nat. Rev. Gastroenterol. Hepatol. 12, 205–17 (2015).
9. Kuek, A., Hazleman, B. L. & Ostör, A. J. K. Immune-mediated inflammatory diseases (IMIDs) and biologic therapy: a medical revolution.
Postgrad. Med. J. 83, 251–60 (2007).
10. Gentschew, L. & Ferguson, L. R. Role of nutrition and microbiota in susceptibility to inflammatory bowel diseases. Mol. Nutr. Food Res. 56, 524–35 (2012).
11. Assa, A. & Shamir, R. Exclusive enteral nutrition for inducing remission in inflammatory bowel disease in paediatric patients. Current
Opinion in Clinical Nutrition and Metabolic Care 20,
384–389 (2017).
12. Ruemmele, F. M. et al. Consensus guidelines of ECCO/ESPGHAN on the medical management of pediatric Crohn’s disease. J. Crohn’s Colitis 8, (2014).
13. Boneh, R. S. et al. Dietary therapy with the Crohn’s disease exclusion diet is a successful strategy for induction of Remission in children and adults failing biological therapy. J. Crohn’s
Colitis 11, 1205–1212 (2017).
14. Cohen, A. B. et al. Symptoms of Inflammatory Bowel Disease. Dig. Dis. Sci. 58, 1322–1328 (2013). 15. Suskind, D. L., Wahbeh, G., Gregory, N., Vendettuoli, H. & Christie, D. Nutritional therapy in pediatric Crohn disease: the specific carbohydrate diet. J. Pediatr. Gastroenterol. Nutr. 58, (2014).
16. Suskind, D. L. et al. Clinical and Fecal Microbial Changes With Diet Therapy in Active Inflammatory Bowel Disease. Journal of Clinical
Gastroenterology 00, 1 (2016).
17. Chiba, M. et al. Lifestyle-related disease in Crohn’s disease: relapse prevention by a semi-vegetarian diet. World J. Gastroenterol. 16, 2484–95 (2010).
18. Olendzki, B. C. et al. An anti-inflammatory diet as treatment for inflammatory bowel disease: a case series report. Nutr. J. 13, 5 (2014).
19. Khalili, H. et al. Identification and Characterization of a Novel Association between Dietary Potassium and Risk of Crohn’s Disease and Ulcerative Colitis. Front. Immunol. 7, 554 (2016). 20. Hou, J. K., Abraham, B. & El-Serag, H. Dietary Intake and Risk of Developing Inflammatory Bowel Disease: A Systematic Review of the Literature. Am. J. Gastroenterol. 106, 563–573 (2011).
21. Brown, A. C., Rampertab, S. D. & Mullin, G. E. Existing dietary guidelines for Crohns disease and ulcerative colitis. Expert Rev. Gastroenterol.
Hepatol. 5, 411–425 (2011).
22. Levine, A. et al. Dietary Guidance From the International Organization for the Study of Inflammatory Bowel Diseases. Clin. Gastroenterol.
1
23. Lewis, J. D. & Abreu, M. T. Diet as a Trigger or Therapy for Inflammatory Bowel Diseases.
Gastroenterology 152, 398-414.e6 (2016).
24. De Vries, J. H. M., Dijkhuizen, M., Tap, P. & Witteman, B. J. M. Patient’s Dietary Beliefs and Behaviours in Inflammatory Bowel Disease. Dig.
Dis. 37, 131–139 (2019).
25. Kamp, K. J., Pennings, B., Javelli, D., Wyatt, G. & Given, B. Dietary patterns, beliefs and behaviours among individuals with inflammatory bowel disease: a cross-sectional study. J. Hum.
Nutr. Diet. 1–8 (2020). doi:10.1111/jhn.12786
26. Duff, W. et al. Non-pharmacological therapies for inflammatory bowel disease: Recommendations for self-care and physician guidance. World J. Gastroenterol. 24, 3055–3070 (2018).
27. Weisshof, R. & Chermesh, I. Micronutrient deficiencies in inflammatory bowel disease.
Current Opinion in Clinical Nutrition and Metabolic Care 18, 576–581 (2015).
28. National Institute for Public Health and Environment. Dutch Food Composition Dataset
(NEVO). (EuroFIR AISBL, 2013).
29. Bolte, L. et al. Towards anti-inflammatory dietary recommendations based on the relation between food and the gut microbiome composition in 1423 individuals - Congress Abstract. United
Eur. Gastroenterol. J. 7, Supplement (2019).
30. National Cancer Institute. Comparing Dietary Assessment Instruments. Dietary
Assessment Primer 1 (2020). Available at: https://
dietassessmentprimer.cancer.gov/profiles/table. html. (Accessed: 24th September 2020)
31. Yanai, H. & Hanauer, S. B. Assessing response and loss of response to biological therapies in IBD. Am. J. Gastroenterol. 106, 685–698 (2011).
32. Willett, W. C. Nutritional Epidemiology. Oxford
University Press (Oxford, 1998). doi:10.1093/ISBN
33. Limdi, J. K., Aggarwal, D. & McLaughlin, J. T. Dietary Practices and Beliefs in Patients with Inflammatory Bowel Disease. Inflamm. Bowel Dis. 22, 164–170 (2015).
34. Yetley, E. A. et al. Options for basing Dietary Reference Intakes (DRIs) on chronic disease endpoints: report from a joint US-/Canadian-sponsored working group. Am. J. Clin. Nutr. 105, 249S-285S (2017).
35. Brotherton, C. S., Taylor, A. G., Bourguignon, C. & Anderson, J. G. A high-fiber diet may improve bowel function and health-related quality of life in patients with Crohn disease. Gastroenterol. Nurs. 37, 206–16 (2014).
36. Higgins, J. P. T. et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ 343, (2011).
