Continued disconnect between biomedical research and dietary fiber recommendations regarding inflammatory bowel diseases
Carol S. Brotherton,1 Richard Kellermayer2*
1George Mason University, School of Nursing, 4400 University Drive, MS 3C4, Fairfax, Virginia, United States of America, 22030; 2Texas Children’s Hospital, Section of Pediatric Gastroenterology, Department of Pediatrics, Baylor College of Medicine and USDA/ARS Children’s Nutrition Research Center, 6701 Fannin Street, Houston, Texas, United States of America, 77030.
*Richard Kellermayer is a physician scientist who has authored over 90 peer reviewed scientific papers, a great number of which focus on Crohn’s disease and ulcerative colitis. He aims to identify the nutritional and environmental reasons for inflammatory bowel disease development. Dr. Kellermayer is an active pediatric gastroenterologist clinician, striving to improve the lives of children and families suffering from Crohn’s disease and ulcerative colitis. He works at the Texas Children’s Hospital, Baylor College of Medicine in Houston, Texas.
The authors declined to resubmit this manuscript during the peer review process in 2015.
RK and CB, no conflicts of interest.
Abbreviations used: IBD, inflammatory bowel disease; CD, Crohn’s disease; UC, ulcerative colitis; IL, interleukin; PCR, polymerase chain reaction; TNF- α , tumor necrosis factor-α.
Dietary fiber remains an important aspect of inflammatory bowel disease (IBD) research today, but the direction of focus has shifted from conventional fiber restriction recommendations to the anti-inflammatory effects of fiber in the gut. Our aims were to review recent fiber/IBD research and to compare fiber recommendations aimed at individuals who search the internet for IBD diet information. Research articles were identified through a PubMed search conducted on April 9, 2015, using the search terms ‘fiber’ and ‘inflammatory bowel disease,’ limited to the previous 5 years. Reviewed articles reported findings from original research in which the title and abstract indicated that fiber was a main focus of an interventional study. Internet websites were identified using a Google search on the phrase, “inflammatory bowel disease and diet,” and the websites appearing on the first page of results were reviewed for fiber information. All 20 reviewed studies tested fiber as a therapeutic agent to reduce gut inflammation – hypothesizing and demonstrating a range of beneficial effects and few adverse events, including investigations of high insoluble fiber diets during active disease. No study hypothesized any anti-inflammatory benefits from overall fiber restriction. The fiber recommendations found in the 13 reviewed websites strongly emphasize fiber restriction. Missing entirely was a layperson-friendly presentation of the scientific concept of dietary fiber as an anti-inflammatory therapeutic agent with implications for chronic bowel inflammation. The effect of dietary fiber on gut inflammation is an under-developed concept in lay literature. There is a need to provide more intense education about dietary fiber, and to update fiber recommendations to help patients safely make informed decisions regarding fiber consumption.
Keywords: dietary fiber, diet, inflammatory bowel disease, Crohn’s disease, ulcerative colitis, short-chain fatty acids, butyrate, cellulose, wheat bran, microbiome
Inflammatory bowel diseases (IBD), primarily Crohn’s disease (CD) and ulcerative colitis (UC), are chronic forms of intestinal inflammation with unknown etiology. The incidence of the disorders has dramatically risen over the past century, especially in the developed world (1, 2). IBD often causes recurring episodes of life-altering symptoms including abdominal pain, intestinal bleeding, and liquid stools. Many patients with IBD use dietary interventions as a complement to pharmacologic therapies, hoping to restore and maintain intestinal health. However, despite aggressive and multi-pronged approaches, it remains difficult for many patients to induce sustainable remission, and symptom flares commonly occur throughout life.
Among the many dietary alterations aimed at reducing gut inflammation and IBD symptoms, dietary fiber was an early focus. Dietary fiber remains an important aspect of IBD research today, but the directions in this respect have shifted from conventional fiber restriction recommendations to a focus on the anti-inflammatory effects of fiber in the gut (3). As IBD emerged throughout the 20th century, fiber restriction was thought to reduce gut inflammation (4-7), and recommendations often linked the terms ‘non-digestible,’ ‘irritating,’ and ‘inflammatory,’ as if these characteristics are interchangeable. Today, researchers appreciate that many non-digestible food components are anti-inflammatory, because microbes have the capacity to metabolize non-digestible food components and produce fatty acids that down-regulate immune responses (8).
The purpose of this review is to compare current gut inflammation/fiber research to dietary fiber information and recommendations aimed at individuals who search the internet for IBD related diet information. In a 2012 survey of patients with long-standing IBD (n = 271), 80 to 89% of respondents regarded dietary information as “very important,” yet only 8 to 16% believed they received adequate guidance (9). In the same cohort, 64% of responders regarded websites as “very acceptable” sources of health information (9). Therefore, it is reasonable to think that individuals with IBD are using the internet to supplement diet information received from health care providers. The question here is whether the 21st century thrust of gut inflammation/fiber research findings is having an impact on the dietary fiber information that is readily available in a layperson’s search of internet websites that address the topic of IBD and diet.
Biomedical research on dietary fiber in IBD
Search strategy. Articles were identified through a PubMed search conducted on April 9, 2015, using the search terms ‘fiber’ and ‘inflammatory bowel disease.’ Publication dates were limited to the previous 5 years.
Article selection. All abstracts generated by the PubMed search were reviewed, and the full article was pulled and reviewed if the abstract met the following criteria: 1) the article reports results from original research that used an interventional design; 2) the study was conducted in IBD patients, on their microbiome, or in an animal, cell line model of IBD; and 3) the title and abstract indicated that fiber was a main focus of the investigation (fiber in general, fiber by a specific name, or fiber referred to as a prebiotic alone or in combination with probiotics).
Data extraction. Data extracted from the studies included the following: standard reference information, country, type of fiber tested, type of sample (humans, animals, or fecal microbiome), rationale for the study, hypotheses, outcome measures, conclusions, and adverse events.
Characteristics of included studies. One hundred and twenty three articles were retrieved in the PubMed search, and 20 articles met the above criteria for review (11 in an animal or cell line model (10-20), 8 in humans (21-28), and 1 in fecal samples from individuals with IBD (29). In addition to five studies conducted in the U.S.A. (13, 16, 20, 22, 28), the effects of fiber on gut inflammation were also investigated during the last 5 years in Canada (10, 12, 13, 18), the U.K. (27), Italy (26), Belgium (23), Denmark (29), Spain (11, 15), Japan (14, 21, 24), Thailand (17), Algeria (19), and Iran (25). All 20 reviewed studies tested fiber as a therapeutic agent to reduce gut inflammation, hypothesizing that provision of fiber produces beneficial effects. No study was found that hypothesized any anti-inflammatory benefits from overall fiber restriction.
Types of fibers tested. Most studies tested a fiber supplement, without changing the overall diet consumed by the individuals or animals. The exceptions were three studies that tested high fiber diets, without a pharmaceutically-prepared fiber supplement. A Japanese intervention tested a lacto-ovo-vegetarian dietary pattern containing 32.4 grams of dietary fiber in 2000 kilo calories (21). Two U.S. studies examined a diet in which whole grains replaced refined grains and participants regularly included Kellogg’s All-Bran Bran Buds®, a grocery store cereal that contains 39 grams of fiber per cup (22, 28).
Various fiber types were examined. Fifteen studies tested one or more soluble fibers (10-12, 14-19, 21, 23, 24, 26, 27, 29). Soluble fibers were either pharmaceutical preparations of oligosaccharides and/or inulin, or foods containing soluble fiber, such as ground flax, oats, and legumes. Most of these researchers based the rationale for their studies on known and/or hypothesized beneficial effects of metabolites that result from bacterial fermentation of fiber (10, 11, 18-21, 24, 27, 29). Some papers cited rationale based on known and/or hypothesized beneficial effects of fiber on the gut microbiota (14, 18) and/or modulation of the intestinal immune system (16, 17). One team highlighted the generally encouraging results of prebiotic (fiber) studies reported in the literature and the reluctance of patients “to undergo a new course of corticosteroids because of previous side effects” as the basis of their research (26).
In addition to examining the effects of soluble dietary fiber, six teams tested substantial amounts of insoluble fiber, either alone (13, 22, 25, 28), or in combination with soluble fibers (20, 21). The lacto-ovo-vegetarian diet tested in Japan contained more insoluble fiber than soluble fiber, 23.3 and 6.8 grams, respectively (21). This latter diet contains fiber “far in excess of the recommended amount for the Japanese population” (21). In a mouse model, Nagy-Szakal and colleagues (2013) examined the effects of diets containing differing amounts of cellulose, an insoluble fiber (13). In two samples of individuals with Crohn’s disease, wheat bran cereal was used: a highly-concentrated source of cellulose, an insoluble fiber (22, 28). In a sample of 41 patients with ulcerative colitis, germinated barley foodstuff (a supplement that consists mainly of insoluble dietary fibers) was tested against standard drug therapy alone (25). In interleukin (IL)-10-deficient mice, the anti-inflammatory effects of insoluble fiber were tested along with several soluble fibers against fructose-based inulin as the reference (20).
The stated rationale for testing therapeutic effects of insoluble and soluble fiber was similar: modulation of gut microbiota (13, 20-22, 25) and production of beneficial metabolites, such as butyrate and other short-chain fatty acids (20-22, 25). However, Nagy-Szakal and colleagues (2013) noted that fermentation of cellulose and production of short-chain fatty acids are limited for cellulose (13). Some of these authors referred to the association between low fiber Westernized diets and IBD prevalence as rationale to investigate the beneficial effects of fiber on gut inflammation, with specific reference to the early epidemiologic work of Denis Burkitt (13, 21, 22, 28), whose writings incriminated lack of cereal fiber as the culprit in the rise of chronic digestive diseases of civilization (30).
Outcome measures. Outcome measures varied widely between the studies. These in clinical studies included the following: remission rate after 2 years (21); Inflammatory Bowel Disease Questionnaire and partial Harvey Bradshaw Index scores (22); real-time polymerase chain reaction (PCR) analysis of the microbiome in fecal samples (23); endoscopic scores, using Matts classification (24); myeloperoxidase analysis of lavage solution collected during colonoscopy preparation (24); serum levels of tumor necrosis factor-α (TNF- α), IL-6, and IL-8 (25); disease activity scores, using the Rachmilewitz disease activity index (26); percentage of patients achieving clinical response and clinical remission, using the Crohn’s Disease Activity Index (score decrease ≥70 and score ≤150, respectively) (27); cytokine production by intestinal dendritic cells, using mucosal biopsies (27); quantification of Bifidobacteria and Faecalibacterium prausnitzii in stool samples, using fluorescent in situ hybridization (27); and fecal calprotectin (27). One study collected and analyzed qualitative data using audio-recorded interviews that were conducted with CD patients before and after and the intervention (28).
Outcome measures in IBD animal models, cell line models, or in fecal samples from humans with IBD included the following: permeability to fluorescein isothiocyanate-dextran;(10) integrity of intercellular tight junctions, using immunofluorescence microscopy to measure intercellular tight junction protein zona occluden-1 (10); real-time PCR analysis of inflammatory markers (10); gene expression (10-12, 20); microbiome composition, using quantitative (q) PCR analysis of colonic contents (10, 11, 16, 18, 29); microbiome composition, using qPCR analysis of cecal contents (18); microbial diversity, using fluorescence in situ hybridization analysis (10); short-chain fatty acid concentrations in fecal samples (10, 11, 18, 29); short-chain fatty acid concentrations in cecal samples (18); analysis of the microbiome from mucosal samples (13); inflammatory gene expression (10); changes in body weight (10, 11, 13, 15); food and/or fluid intake (10, 11); stool consistency (14); hemoccult testing (14); colon macroscopic visible damage score (11, 16, 20); cecum macroscopic visible damage score (16); colon length (13, 14, 17, 19); colonic weight to length ratio (15); plasma cytokine concentrations, measured by enzyme-linked immunosorbent assay, including IL-6, IL-8, and TNF- α (12); proinflammatory cytokine expression in colonic mucosa, using real-time PCR, including IL-1β (14, 18), TNF-α (14, 17), and IL-6 (17); cytokine production in spleen and Peyer’s Patches (20); histological severity of intestinal inflammation (11, 13, 14, 17-20); myeloperoxidase activity (15, 17); inducible nitric oxide synthase expression (15); nitric oxide production (19); percentage of natural killer cells in the spleen and mesenteric lymph nodes (16); natural killer cell expression of chemokine receptors and L-selectin (16); IL-15 concentration in proximal colon tissue (16); nuclear factor kappa beta DNA binding activity (17); lipopolysaccharide- and TNF-α-induced inflammatory responses and mucosal barrier disruption in IEC (17); LPS binding to intestinal epithelial cells (17); TNF- α and H2O2-induced apoptosis in T84 cells (17); and pH of fecal contents (29).
Tolerability. Except for one clinical study (25), all of the human subjects recruited for these investigations included patients with active symptoms at baseline. Of the three studies that tested a diet that included fiber-containing foods, good tolerance was either overtly stated (22, 28) or implied (21). Of the five studies that tested a fiber supplement, an assessment of tolerance was not found in three studies (24-26). Two articles reported substantial intolerance to the fiber supplement tested (23, 27), both of which were soluble fiber supplements, specifically fructo-oligosaccharides (27) and oligofructose-enriched inulin (23). In these two studies, significantly more participants withdrew from the intervention groups due to side effects such as flatulence, borborygmi, and abdominal pain than from the respective control groups. Attrition rates were 32% (23) and 26% (27) in the intervention groups, compared to 12% (23) and 8% (27) in the control groups, p=0.07 and p=0.0018, respectively).
Adverse Events. Generally, few adverse events were found in these articles. In one study, there was an unexpected death of one mouse (19). In a sample of 103 patients with active CD at baseline, serious adverse events were reported in six patients; four of these participants were receiving the active intervention and two were receiving placebo; four events were related to disease deterioration, of which, three were in the intervention group (27). The remaining two adverse events in this study were an asthma attack in the intervention group and a car accident in the placebo group (27). No other adverse events were recorded.
Conclusions. The effect of fiber on gut inflammation is an immense and complex topic of research. It is beyond the scope of this paper to present a comprehensive review of the results and conclusions from 5 years of fiber/gut inflammation research. In general, current researchers hypothesized and have demonstrated a range of beneficial effects from fiber with respect to gut inflammation in animals and humans.
Recent biomedical research overwhelmingly favors dietary fiber in the setting of IBD. However, not every investigated mechanism was supported by the findings. At least two teams concluded that caution is needed when considering therapeutic use of fiber for IBD. Benjamin and colleagues (2011), reported high attrition in patients with active Crohn’s disease who were receiving fructo-oligosaccharide (a soluble fiber supplement). They recommended that fiber supplements should be investigated for IBD remission maintenance, instead of remission induction (27). Kuo and colleagues (2014), who found that prebiotic/probiotic supplementation increased proinflammatory gene expression in IL-10-null mice, recommend that disease and genetic background be considered before using prebiotic/probiotic supplementation.
IBD Diet Information on the Internet
Search strategy. On May 20, 2015, Google was used to search on the phrase ‘inflammatory bowel disease and diet.’ The search yielded more than 1.3 million listings. The first page of results was copied and pasted into a Word document for later analysis and a brief description of the websites. Links contained in the first page were followed and the linked webpages were copied and pasted into Word documents for later analysis. Subsequent links continued to be followed and pages copied and pasted for as long as the information was judged to be of interest to an individual trying to learn what to eat with IBD. Websites were assessed for the content of fiber information provided: information regarding a low fiber diet, information regarding a high fiber diet, absence of fiber information, or presence of other fiber information.
Initial results (first page of the resulting website list). Fourteen websites were listed on the first page of search results. The first three websites at the top of the list were labeled as advertisements; of these, two were sponsored by pharmaceutical companies and were included in analysis. The third advertisement was excluded, because it was sponsored by a laboratory that diagnoses irritable bowel syndrome. The fourth listing was labeled ‘Scholarly articles for inflammatory bowel disease and diet,’ under which three sub-links displayed the following partial titles: ‘Clinical epidemiology of inflammatory bowel disease,’ ‘Inflammatory bowel disease: etiology and…’, and ‘Diet and inflammatory bowel disease: a case-control…’ Of the remaining 10 websites in the list, two were sponsored by the Crohn’s and Colitis Foundation of America (CCFA), two were sponsored by WebMD, two were sponsored by the Mayo Clinic, and one was sponsored by each of the following: Health.com, Nutrition Journal, the University of California – San Francisco, and Wikihow. In Table 1, the complete list of websites is shown by title and web address, in the order that these appeared in the list.
Following the links. Websites with low fiber diet recommendations: Of the 13 websites reviewed, 10 recommend some form of fiber restriction for individuals with IBD. Some websites express overt caution against fiber in general – for example, the Mayo Clinic states that “high fiber foods, such as fresh fruits and vegetables and whole grains may make your symptoms worse” (#11), and health.com’s Tips for Living with IBD, #6 and # 7, are entitled, “Try a Reduced Fiber Diet” and “Avoid Roughage,” respectively. WebMD generally recommends avoiding “foods high in fiber,” “whole grains,” and “bran” (#10). One website more subtly steers individuals with IBD away from ingesting dietary fiber by listing and describing a “White Diet” under the heading of “Commonly Discussed Diets” for IBD (#2); furthermore, the site offers a grocery list of IBD-friendly foods such as white bread, white pasta, saltines, and white rice, but the list includes no whole grains (#2).
Other websites caution against fiber more selectively, by targeting fiber consumption during special circumstances, such as during flares (#5, 6, 8, and 14), after surgery (#8), in the presence of strictures (#8), or if fiber seems to “bother” the individual (#9). Some websites also express caution selectively, by recommending fiber-avoidance based on the type of fiber, encouraging the consumption of soluble fiber but recommending against the consumption of insoluble fiber (#7, 8, and 13), or recommending modification of the texture of fiber through blenderizing, grinding, or cooking (#13).
The scholarly article linked to Website #13 reports the findings from a study that tested an “anti-inflammatory” diet in individuals with IBD who were either refractory to pharmacological therapy or who had experienced inadequate resolution of IBD symptoms. The intervention diet places strong emphasis on the ingestion of foods with soluble fiber; however, concurrent emphasis was placed on avoiding “intact” fiber, reinforcing the above expressions of caution concerning some forms of fiber.(31)
Websites without low fiber diet recommendations. Recommendations to restrict dietary fiber were not found in three analyzed websites (#1, 4, and 12). Website #1 makes no statement regarding fiber for individuals with ulcerative colitis and simply states “experiment with fiber” for Crohn’s disease. Website #4, which has three scholarly articles sub-linked beneath the main title, provides almost no information about fiber. Only two of the articles mention fiber (1, 32), and the information is minimal and not geared to a general audience lacking understanding of epidemiological data analysis. In contrast to the first Mayo Clinic webpage that recommends a low fiber diet (#11), the Mayo Clinic webpage entitled, “Inflammatory Bowel Diseases – Treatment and Drugs” (#12) makes no mention of a low fiber diet to treat IBD. In fact, in the second Mayo Clinic website, fiber supplementation is suggested as an IBD treatment—under the heading “Anti-diarrheal medications,” two specific dietary fibers are listed: psyllium powder (a soluble fiber) and methylcellulose (an insoluble fiber).
Websites with an explanation of fiber benefits. An explanation of the known and hypothesized beneficial effects of dietary fiber in the gut was not found in any of the 13 reviewed websites. Only a few general statements of benefit from fiber were found, such as “fiber is essential for health and digestion” (#8) and statements regarding the need to restore fiber to the diet after flares subside or surgical sites heal (#5 and 8). The Mayo Clinic mentioned relief from diarrhea using the bulking action of soluble and insoluble fiber (#12), and the Nutrition Journal article (#13) referenced the potential for fiber to address dysbiosis associated with IBD. Missing from all 13 websites is a layperson-friendly presentation of the scientific concept of dietary fiber as an anti-inflammatory therapeutic agent with implications for chronic bowel inflammation.
The concepts around dietary fiber for individuals with IBD has dramatically changed since the early 1900s, when a low fiber diet was the standard dietary regimen for IBD (4-6). Yet, some recommendations against fiber found in this analysis still resemble the prior generalized anti-fiber messages. Only some of today’s websites present low fiber recommendations that are tempered, suggesting fiber be avoided only in certain circumstances and specifying types of fibers to be avoided. Notably, the Diet, Nutrition, and Inflammatory Bowel Disease 2013 brochure (Website #8) offers two sample meal plans that suggest daily fiber totals of 31 grams and 38 grams – a stark contrast to the low fiber recommendations that predominated dietary guidance prior to the advancement of IBD/fiber research in recent decades (4-7). Perhaps the clearest indication of the impact from decades of IBD/fiber research is that the Mayo Clinic has advanced to the point of listing fiber supplements, both soluble and insoluble, as medications to help relieve mild to moderate diarrhea associated with IBD (Website #12).
Despite clear progress, considering the 20 IBD/fiber intervention studies conducted during the past 5 years, it is concerning that web-based messages 1) have strong recommendations against insoluble fiber, and 2) suggest that fiber should be avoided when IBD symptoms are active. These messages indicate there has been an incomplete impact from recent advances in IBD/fiber research. Investigators are testing both soluble and insoluble fiber in individuals with active symptoms, and the findings are encouraging overall – tolerability has been good, with the most significant intolerance noted in two studies that tested soluble fiber supplements.
Three clinical studies included patients with active symptoms and focused primarily on consumption of ultra-high quantities of insoluble fiber (21, 22, 28), yet no adverse events were reported as a result of consuming ultra-high quantities of insoluble fiber in the presence of active IBD symptoms. In one study, maintenance of remission at 2 years was 100% for combined biologic and diet therapy, and maintenance of remission at 2 years was 92% for diet therapy alone (21). In another study, four of four participants randomized to receive an ultra-high insoluble fiber diet reported resolution of all abdominal pain and liquid stools by the end of the 4-week study; whereas, three of three participants randomized to receive standard IBD diet continued to have IBD symptoms, including abdominal pain and liquid stools throughout the study (22). In the third publication, participants who were interviewed after receiving information about the benefits of fiber (primarily insoluble fiber) reported that they began eating a daily serving of Kellogg’s All-Bran Bran Buds® and observed beneficial effects on gastrointestinal function throughout the 4-week study (28). Algieri and colleagues (2014) hypothesize that delayed fermentation of some fibers could account for greater tolerability and suggest greater effectiveness to benefit distal segments of bowel affected by IBD (11). Interestingly, insoluble fiber (specifically wheat bran) has been shown to shift the site of fermentation of resistant starch distally in pigs (33). Based on this biomedical research, we strongly recommend the supplementation of both soluble and insoluble fiber to the limit of tolerance in IBD patients, especially for the majority who have primarily inflammatory, non-complicated disease for years after diagnosis (34, 35). Widely accessible web based information, however, does not mirror these recommendations.
Most concerning from this analysis is that website readers will not learn that non-digestible food components have anti-inflammatory potential. Instead, readers of these websites will be cautioned about fiber and only receive rare encouragement to return to more ‘normal’ dietary habits during remission. Fewer than 3% of Americans eat the recommended amount of dietary fiber in most age and gender groups (36, 37). Consequently, without a firm understanding of the anti-inflammatory effects of fiber, it is doubtful that individuals with IBD who read these websites will be inspired to consume a healthy amount of fiber. Instead, readers may easily conclude that if a low fiber diet is supposed to help resolve a flare, then avoiding fiber indefinitely may help prevent a flare.
In conclusion, the effect of dietary fiber on gut inflammation is an under-developed concept in lay literature. Scientists, and even clinicians (23, 26) are demonstrating their confidence in fiber to improve IBD outcomes. Our website analysis suggests that there is a need to alert patients about this important paradigm shift, to provide more intense education about dietary fiber, and to update fiber recommendations to help patients safely make informed decisions regarding fiber consumption.
This analysis is limited by the small number of websites analyzed. More than 1.3 million websites were generated by the Google search, but only the websites on the first page were analyzed. Individuals searching for IBD/diet information may find very different fiber information than has been included in this analysis.
RK would like to acknowledge the Gutsy Kids Fund including philanthropic donation from the Karen and Brock Wagner family, and the support of the Houston Men of Distinction
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