Advance nutrition essay

INVITED COMMENTARY

Dietary Fiber and Gastrointestinal Disease: an Evolving Story

John O’Grady1 & Fergus Shanahan1

Published online: 8 November 2018 # Springer Science+Business Media, LLC, part of Springer Nature 2018

Overview

Denis Burkitt, working in Africa in the 1970s, was one of the first to suggest a link between a diet deficient in fiber and gastrointestinal disease [1, 2]. While initially embraced by gastroenterologists and applied to a diversity of gastrointesti- nal ailments, subsequent studies were discouraging, could not confirm many of the putative clinical benefits of fiber, and enthusiasm waned [3]. This was, in part, due to simplistic concepts of fiber-related health benefits which are being supplanted with enhanced understanding of the physiological properties of different types of fiber. For example, the solubil- ity, viscosity, and fermentation properties of fiber are now known to be determinants of the favorable impact of fiber on host metabolism [4]. Moreover, advances in microbiome sci- ence have affirmed the importance of gut microbiota in fiber fermentation and host metabolism [5]. It seems likely that, in the future, the efficacy criteria for assessing fiber supplements will be metabolic parameters rather than traditional markers of gastrointestinal disease. This brief commentary reflects the changing role of fiber in irritable bowel syndrome, inflamma- tory bowel disease, diverticulosis, and colorectal cancer, and recommends that future studies should adopt microbial anal- yses and switch toward metabolic targets in the host.

Irritable Bowel Syndrome

When recommended by gastroenterologists without heed to the specific properties of the type of fiber, the inescapable truth has been that many patients with irritable bowel

syndrome (IBS) complain that fiber exacerbates their symp- toms. It has emerged that the effects of fiber in IBS are, in part, determined by the solubility, viscosity, and fermentation prop- erties of individual fibers [4, 6]. Pain and bloating may be exacerbated by readily fermentable short-chain fibers due to rapid and excessive gas production [7]. This may account for some of the benefit experienced by a subset of patients with a temporary diet low in fermentable oligosaccharides, disaccha- rides, monosaccharides, and polyols (FODMAPs) [8, 9]. In contrast, longer-chain, soluble fibers with limited in vivo fer- mentation tend to improve overall symptoms for patients with IBS [7]. Psyllium, consisting of arabinoxylan and sourced from Plantago ovata [10], is a dietary fiber with each of these properties. Among patients with chronic diarrhea, psyllium improves stool consistency and urgency more effectively than loperamide, though both therapies reduce frequency of bowel motions [11]. Psyllium supplementation also improves bowel motion frequency and total stool output among patients with chronic constipation compared with docusate [12] or placebo [13, 14].

One potential mechanism by which fiber might improve some patients with IBS is a bifidogenic effect. The strain- specific efficacy of a bifidobacterium (B. infantis 35624) in IBS has been demonstrated by Whorwell and colleagues in a large placebo-controlled trial [15]. It is, therefore, noteworthy that GOS fiber supplementation in IBS significantly increases levels of bifidobacteria while reducing IBS-related symptoms [16]. Since patients with IBS tend to have lower levels of bifidobacteria compared with healthy controls [17, 18], die- tary fiber-microbe interactions may facilitate identification of a subset of patients likely to benefit most from fiber supplementation.

Inflammatory Bowel Disease

Early studies of fiber in inflammatory bowel disease (IBD), particularly Crohn’s disease, prioritized clinical response and

* John O’Grady [email protected]

1 Department of Medicine and APC Microbiome Ireland, University College Cork, National University of Ireland, Cork, Ireland

Current Gastroenterology Reports (2018) 20: 59 https://doi.org/10.1007/s11894-018-0667-0

remission with little evidence of benefit [19]. Moreover, re- stricted fiber intake reduces obstructive symptoms for patients with IBD-related strictures. Symptomatic improvement among this group of patients likely contributed to dubious low dietary fiber advice for all patients with IBD. Even in remission, patients with IBD consume less fiber than healthy controls [20]. While there is little current evidence for fiber in inducing or maintaining remission in IBD, there is no evi- dence for restricting fiber in the absence of stricturing disease [21].

The true benefit of fiber in the context of IBD may relate to its influence on the microbiota and in maintenance of mucosal integrity. In murine models, low fiber intake results in disrup- tion of the mucus layer by fiber-deprived microbiota which increases susceptibility to pathogens and inflammation [22]. Additional influences of fiber on mucosal homeostasis include the upregulation of interleukin (IL)-10, toll-like receptor (TLR) 2, and TLR4 expression [23, 24] by fructooligosaccha- ride (FOS) fiber. Furthermore, inulin fiber is associated with increased butyrate, as well as having a bifidogenic effect [25, 26]. Butyrate, a short-chain fatty acid (SCFA) produced by fermentation of fiber by microbiota, has anti-inflammatory and mucosal immune regulatory properties [27]. Recently, a reduced capacity of the microbiota for butyrate synthesis has been observed in Crohn’s disease and active ulcerative colitis, which may relate to reduced dietary fiber intake and contribute to the pathogenesis of IBD [28].

Whether such immunomicrobial exchanges can be thera- peutically exploited remains to be determined, but increasing fiber intake for patients with IBD is a significant challenge. Recommendations for patients with IBD to consume more dietary fiber may relate more to the metabolic benefits [4] rather than anti-inflammatory effects of fiber, since many pa- tients with IBD are now either overweight or obese [29, 30].

Diverticular Disease

Despite uncertainty due to a lack of high-quality data either to confirm or reject fiber as a management adjunct, high fiber diet remains part of many recommended guidelines for the management of diverticular disease [31]. This is probably be- cause reduced fiber intake has been associated with presence of diverticula, but dietary deficiency of fiber is unlikely to be the sole cause [31]. Other contributory factors include excess consumption of red meat, aging, loss of microbial diversity, and medical co-morbidity [31]. Furthermore, changes in the microbiota in close proximity to diverticula may be an impor- tant step in the inflammatory process [32] and is, perhaps, a clue to the combined influence of fiber and the microbiome in disease pathogenesis. To explore this, one study randomized 52 patients with uncomplicated diverticular disease to receive either high fiber diet with additional Lactobacillus paracasei

B21060 or high fiber diet alone [32]. Significant reductions in abdominal pain were seen in both treatment limbs, but only the patients receiving additional probiotic had a significant reduction in bloating. The lack of a placebo group limits in- terpretation, and larger, double-blind, placebo-controlled trials are required.

Reversal of diverticular disease by diet is an unrealistic proposition although modest reduction of symptoms with fi- ber in some patients may be achievable. The more likely role for fiber is in prevention. Prospective analysis, albeit uncon- trolled, observational, has been encouraging and suggests that fiber from cereal and fruit has a role in reducing risk of diver- ticulosis [33].

Colorectal Cancer

Proposed mechanisms for dietary fiber in the reduction of colorectal cancer risk have included dilution of fecal carcino- gens, quicker gut transit times, binding of carcinogenic bile acids, and alterations in microbiota composition and microbial metabolites, such as SCFA, production [34]. However, as with many early claims, the role of dietary fiber in colorectal cancer risk has been challenged because of insufficient evidence to suggest that increased fiber intake reduces the incidence or recurrence of adenomatous polyps [3]. Regardless, meta- and pooled analyses indicate an inverse relationship between fiber intake and risk of incident colorectal cancer [34–37], although this link is not evident for recurrent adenoma risk [38, 39]. Thus, fiber may have a role in reducing the incidence, but not recurrence, of colorectal adenoma and cancer. As with prevention of diverticulosis, an early and sustained fiber- enhanced diet needs scrutiny in prospective controlled trials.

Dietary fiber intake influences microbiota composition and, therefore, the effect of microbial metabolites on the host. For example, butyrate produced by fermentation of fiber by gut microbiota, modulates the immune system with potential anti-cancer impact [40]. With increasing attention on the com- positional variability of the microbiota as a risk factor for colorectal carcinogenesis, diet-microbe interactions may play a greater role in the future as preventative strategies long be- fore the onset of disease and well in advance of the current age at which screening is applied.

Conclusion

Contemporary dietary fiber intake (12–19 g/day) is a fraction of ancestral intake (up to 100 g/day), and even of recommend- ed current guideline intake (20–35 g/day) [10, 41]. Reasons for this include changes in agricultural practices, socio- economic and cultural developments [41], and poor under- standing of health roles of fiber. Modern fiber science is re-

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examining the variable properties and physiological effects of different fiber types on the microbiota and on host metabolism and immunity [42–44]. Since the composition of the microbi- ota may predict those who are likely to benefit from fiber supplementation, the prospect and promise of personalized fiber diets may be realized [45]. While fiber may have modest benefit in prevention of certain gastrointestinal diseases, met- abolic outcomes such as weight regulation and lipid and glu- cose metabolism may be a more fruitful area for exploration in the future.

Funding The authors are funded in part by Science Foundation Ireland (APC/SFI/12/RC/2273) in the form of a research center, APC Microbiome Ireland.

Compliance with Ethical Standards

Conflict of Interest John O'Grady is funded through APC Microbiome Ireland. Fergus Shanahan is a co-founder, shareholder in Atlantia Food Clinical Trials, 4D Pharma Cork Ltd., Alimentary Health Ltd. He is the director of the APC Microbiome Ireland, a research center funded in part by Science Foundation Ireland (APC/SFI/12/RC/2273).

Ashley Thomas, Silvio de Melo Jr., and Bruno Ribeiro declare no conflict of interest.

Human and Animal Rights and Informed Consent This article does not contain any studies with human or animal subjects performed by any of the authors.

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