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The term ‘dietary fibre’ was first coined in 1953, and from the 1970s onwards attempts to provide formal defini- tions have continued in light of the growing evidence of its associated health benefits1,2. In 2009, following nearly 20 years of discussions, the World Health Organization and Codex Alimentarius provided a globally dis- seminated and updated definition (Box 1). Analytical methods to quantify dietary fibre have evolved alongside the updated definitions, although data derived from these updated methods are not comprehensively available in all food composition databases (Box 1). Investigating the health effects of fibre is complicated by variations in the interventions. Studies can investi- gate synthetic fibres consisting of only one type of mol- ecule (for example, fructo- oligosaccharides), extracted fibres from naturally occurring plant sources consist- ing of one, or a limited number of fibres (for example, alginate or psyllium), single foods containing a limited number of naturally occurring fibres that are intrinsic and intact in plant cells (such as prunes or wholegrain cereals), and high- fibre diets consisting of a wide range of different naturally occurring fibres from a wide range of different foods. The variations in fibre interventions have created numerous challenges in interpreting and applying the findings. Firstly, in vitro and animal studies have frequently used synthetic or extracted fibres in supplemental form, but whose physicochemical char- acteristics such as molecular weight and bioaccessibility might be different when consumed as whole foods and as part of diets that can affect their functional properties, and secondly because high- fibre foods and diets contain other nutrients and food components (such as vitamins and polyphenols) that could be beneficial to health and, therefore, identifying the effect of fibre alone can be challenging. Dietary fibre has been shown in an extensive num- ber of epidemiological and interventional studies to have important associations with the development and management of various diseases and with mortality. For example, in 2015, the Scientific Advisory Committee on Nutrition (SACN)3 in the UK performed meta- analyses of epidemiological studies of fibre in the prevention of disease, and showed that for each increase in dietary fibre intake from food of 7 g per day there was a statisti- cally significantly reduced risk of cardiovascular disease (relative risk (RR) 0.91, 95% CI 0.88–0.94; P < 0.001), haemorrhagic plus ischaemic stroke (RR 0.93, 95% CI 0.88–0.98; P = 0.002), colorectal cancer (CRC; RR 0.92, 95% CI 0.87–0.97; P = 0.002), rectal cancer (RR 0.91, 95% CI 0.86–0.97; P = 0.007) and diabetes (RR 0.94, Dietary fibre in gastrointestinal health and disease Samantha K. Gill, Megan Rossi, Balazs Bajka and Kevin Whelan ✉ Abstract | Epidemiological studies have consistently demonstrated the benefits of dietary fibre on gastrointestinal health through consumption of unrefined whole foods, such as wholegrains, legumes, vegetables and fruits. Mechanistic studies and clinical trials on isolated and extracted fibres have demonstrated promising regulatory effects on the gut (for example, digestion and absorption, transit time, stool formation) and microbial effects (changes in gut microbiota composition and fermentation metabolites) that have important implications for gastrointestinal disorders. In this Review, we detail the major physicochemical properties and functional characteristics of dietary fibres, the importance of dietary fibres and current evidence for their use in the management of gastrointestinal disorders. It is now well- established that the physicochemical properties of different dietary fibres (such as solubility, viscosity and fermentability) vary greatly depending on their origin and processing and are important determinants of their functional characteristics and clinical utility. Although progress in understanding these relationships has uncovered potential therapeutic opportunities for dietary fibres, many clinical questions remain unanswered such as clarity on the optimal dose, type and source of fibre required in both the management of clinical symptoms and the prevention of gastrointestinal disorders. The use of novel fibres and/or the co- administration of fibres is an additional therapeutic approach yet to be extensively investigated. King’s College London, Department of Nutritional Sciences, London, UK. ✉e- mail: kevin.whelan@ kcl.ac.uk https://doi.org/10.1038/ s41575-020-00375-4 REvIEWS Nature reviews | GastroenteroloGy & HepatoloGy mailto:kevin.whelan@ kcl.ac.uk mailto:kevin.whelan@ kcl.ac.uk https://doi.org/10.1038/s41575-020-00375-4 https://doi.org/10.1038/s41575-020-00375-4 http://crossmark.crossref.org/dialog/?doi=10.1038/s41575-020-00375-4&domain=pdf 95% CI 0.90–0.97; P = 0.001). In 2019, a meta- analysis of 185 epidemiological cohort studies including just under 135 million person- years echoed these findings, showing that risk reduction is greatest when dietary fibre intake from food is between 25 g per day and 29 g per day. This higher fibre intake was associated with reduced risk of all- cause mortality (RR 0.85, 95% CI 0.79–0.91) and mortality from coronary heart disease (RR 0.69, 95% CI 0.60–0.81) and cancer (RR 0.87, 95% CI 0.79–0.95), and with lower incidence of coronary heart disease (RR 0.76, 95% CI 0.69–0.83), stroke (RR 0.78, 95% CI 0.69–0.88), type 2 diabetes mellitus (RR 0.84, 05% CI 0.78–0.90) and CRC (RR 0.84, 95% CI 0.78–0.89)4 compared with lower fibre intake. Both observational analyses highlight the critical importance of the quantity of fibre required to elicit health benefits5,6. These well- established asso- ciations between dietary fibre intake and health have resulted in the majority of countries recommending a daily intake for adults of 25–35 g per day. Despite this recommendation, the average intake of dietary fibre by adults worldwide remains low, typically under 20 g per day7. As well as disease prevention, dietary fibre has the potential to be used as a therapeutic intervention, in par- ticular for disorders of the gastrointestinal tract. National and international guidelines provide some recommen- dations in relation to dietary fibre in the treatment of gastrointestinal disorders such as irritable bowel syn- drome (IBS)8,9, inflammatory bowel disease (IBD)10 and diverticular disease11,12, and in the management of spe- cific gastrointestinal symptoms such as constipation12,13. However, these recommendations are often limited, fail- ing to provide specifics in terms of the type and dose of fibre, and are sometimes even conflicting. The limited number and quality of studies as well as the variations in the fibre interventions (including fibre type, source, dose and duration of treatment) represent key challenges to providing recommendations for the therapeutic use of dietary fibre in the treatment of gastrointestinal dis- orders. The potential of dietary fibre for gastrointesti- nal health and as a therapeutic agent in gastrointestinal disorders is attributed to its effect on nutrient diges- tion and absorption, improving glycaemic and lipae- mic responses, regulating plasma cholesterol through limiting bile salt resorption, influencing gut transit, and microbiota growth and metabolism. Mechanistic research has highlighted the diverse physico chemical characteristics of different dietary fibres, such as solubility, viscosity and fermentability, all of which determine their function in the upper and lower gastrointestinal tracts. The aim of this Review is to discuss the physicochem- ical and functional characteristics of dietary fibres and the effect of these factors on the clinical application of fibre in the management of gastrointestinal disorders, with a focus on studies in humans wherever possible. Physicochemical characteristics Themajority of dietary fibres are the structural polysac- charide components of plant cell walls (Fig. 1; TaBle 1). Cell walls contain multiple polysaccharides and the complexity in elucidating their functions results from the variety of sources and their functions within the cell. This aspect is most evident in the variation in their molecular structure, which includes the composition of the polymer subunits, but also extends to the poly- mer linkages and side- chains (esterification)14. These differences in molecular structure of dietary fibres can substantially alter their physicochemical properties and their behaviour in the gastrointestinal tract. For example, their resistance to intestinal digestion can result from the spatial orientation of polymer subunits, branching, or the presence of side- chains15. Food processing provides an additional level of com- plexity. Indeed, both milling and cooking can also be important determinants of the physicochemical char- acteristics of dietary fibres, improving starch digesti- bility and degradation of plant- derived compounds16. However, some digestible polysaccharides can also be classified as dietary fibre due to their inaccessibil- ity to digestive enzymes within the food matrix, such as type 1 resistant starch (RS-1; as in whole grains) or type 3 resistant starch (RS-3; retrograded), in which resistance can be conferred following cooking and cooling17. The consequence of these small variations in structure is that dietary fibres can have very different physicochemical characteristics (for example, viscos- ity and fermentability) that influence their functional effects (such as gut transit time or the microbiota) in the gastrointestinal tract. Fibre solubility. Solubility refers to the extent to which dietary fibres can dissolve in water. Unlike insoluble fibres that remain as discrete particles, soluble fibres have a high affinity for water18. In cases in which it is necessary to divide the dietary fibre content into soluble and insoluble fibre fractions, the enzymatic–gravimetric assay is often used for routine analysis (Association of Official Analytical Chemists method 2011.25). Examples of carbohydrate polymers whose structure affects their solubility are starch (amylose and amylo- pectin) and cellulose. The former is composed of α- glucose monomers and the latter β- glucose. The cor- responding secondary structures result in starch being soluble (most of which is digested in the small intestine) and cellulose being insoluble (and therefore classified as dietary fibre)18. However, although β- glucose monomer Key points • Dietary fibre has been shown to have a number of important associations with the development and management of various diseases and with mortality in epidemiological and interventional studies. • Dietary fibre has physicochemical characteristics (for example, solubility, viscosity, fermentability) that determine its functionality in the gastrointestinal tract, including its effects on, for example, micronutrient availability, gut transit time, stool formation and microbial specificity. • Current dietary fibre recommendations are often limited and conflicting, and fail to provide specific types and doses in the treatment of gastrointestinal disorders including irritable bowel syndrome, inflammatory bowel disease, diverticular disease and functional constipation. • Future research that considers the influence of differing physicochemical characteristics on functionality will potentially maximize the effect of clinically meaningful symptom improvement in gastrointestinal disorders. www.nature.com/nrgastro R e v i e w s linkages can result in β(1,4)- cellulose being insoluble, they can result in β(1,3)(1,4)- glucan (mixed linkages in β- glucan) being soluble19. Similarly, branching of the polymer structure, such as in amylopectin, β- glucan or inulin, can also affect solubility. Interestingly, the branching in amylopectin can result in increased solu- bility, whereas branching in β- glucan decreases solubility. Additionally, some fibres, such as pectin or methyl cellu- lose, contain side- chains along the polymer that provide resistance to digestion20 whilst also increasing solubility21. The majority of current evidence has focused on solu- bility as a characteristic of fibre in relation to its effect on the upper gastrointestinal tract through the regulation of gastric emptying and nutrient absorption. Indeed, early in vitro studies of isolated fibres allowed the distinction between those that primarily affect small intestinal lipid and glucose absorption and those that primarily affect colonic function such as stool bulking and reduced tran- sit time (insoluble fibres such as cellulose, wheat bran and lignin)22. Thus, classifying fibres based upon solubil- ity was for many decades used to allude to differentiation of their functional properties. However, in 2003 the Food and Agriculture Organization of the United Nations proposed that these conventionally classified terms relating to solubility should be phased out for a num- ber of reasons23. Firstly, measuring and classifying fibre solubility in vitro is method- dependent. Secondly, the varying pH conditions within the gastrointestinal tract (such as stomach versus colon) and between individuals might affect fibre solubility in vivo24,25. Thirdly, solubil- ity alone does not predict the physiological effects of fibre and, therefore, its functional properties. For exam- ple, both psyllium (soluble) and cellulose (insoluble) have been shown to improve glycaemic control, transit time and stool output, albeit via different mechanisms. Glycaemic control in humans is improved by psyllium26 through a mechanism involving increased viscosity of intestinal contents, whereas in rats, cellulose has been shown to affect glycaemia via inhibition of starch diges- tion by binding α- amylase27, thereby reducing glucose absorption28. A further challenge to the use of fibre solubility as an indicator of functionality is that, in reality, whole fibrous foods are often a complex mix of soluble and insoluble fibres (for example, resistant starch, hemicelluloses, cel- lulose and lignin) and, therefore, simultaneously exert different physiological effects in the gastrointestinal tract. For example, apples contain soluble (pectins) and insoluble (cellulose) fibre fractions. It has been suggested that the effects of both soluble (that is, swelling via water absorption) and insoluble (that is, bulking) fibres in the ileum might activate the ileal brake (negative feed- back mechanism that results in inhibition of gastro- intestinal motility and secretion) via mediators such as glucagon- like peptide 1 (GLP1) and GLP2 according to animal research29. Nonetheless, although solubility per se is a poor indicator of physiological function in isolation, it has a profound effect on other factors that have since gained recognition for their specific physiological and microbial actions in the gastrointestinal tract such as viscosity and fermentability. Fibre viscosity. Viscosity is the degree of resistance to flow. It is generally associated with soluble dietary fibres (such as gums, pectins, β- glucans and psyllium) and relates to the ability of a fibre, when hydrated, to thicken in a concentration- dependent manner30. Some forms of fibre, such as pectins, have the capacity to form gel networks. In the gastrointestinal tract, this process can begin in the mouth and continues throughout the digestive tract31. There are several physicochemical char- acteristics that contribute to the viscosity potential of fibre, including the length and structure of the polymer as well as its charge. These factors affect the ‘type’ of gel formed and the critical concentration required for the formation of a viscoelastic gel. Broadly, viscous fibres can be categorized into two groups: random coil poly- saccharidesand ordered assembly polymers. Random coil polysaccharides increase viscosity through entan- glement, thereby restricting the flow of the surround- ing solvent32. Examples include the neutral polymers β- glucans, psyllium and guar galactomannan, in which generally the longer the polymer (that is, the higher the molecular weight), the greater the entanglement that occurs and, therefore, the lower the concentration required to increase viscosity33. By contrast, ordered assembly polymers, such as some pectins and alginate, form a gel network in the presence of divalent ions (that is, Ca2+)33. Increasing gut luminal viscosity has been sug- gested to have multiple health benefits. Consumption of viscous dietary fibre has been shown to alter transit time Box 1 | Definition of dietary fibre and approaches to its chemical analysis Dietary fibre definition • Dietary fibre as defined by the World Health Organization and Codex Alimentarius (collection of internationally recognized standards, guidelines and codes of practice) includes all carbohydrates that are neither digested nor absorbed in the small intestine and have a degree of polymerization (DP) of ten or more monomeric units205,206. • The Codex Alimentarius dietary fibre definition has been adopted by many countries and this has encouraged international consistency in nutrition labelling, food composition tables and published research. • There is flexibility in the definition enabling regional authorities to include carbohydrates with a DP of three to nine monomeric units in the fibre definition. Subsequently, the European Food Safety Authority (EFSA)5 and the FDA6 adopted the wider definition of dietary fibre to include all carbohydrates that are neither digested nor absorbed in the small intestine and have a DP of three or more monomeric units. • Both EFSA and the FDA specify that synthetic and extracted fibres that are not intrinsic to plant cells must also demonstrate physiological effects to human health prior to being declared a dietary fibre. • Codex- defined fibre includes non- starch polysaccharides such as cellulose, hemicelluloses and pectins, resistant starch and non- digestible oligosaccharides such as inulin and oligofructose, as well as lignins. Thus, foods high in dietary fibre include wholegrains, legumes, vegetables, fruits, nuts and seeds. Dietary fibre analysis • Analytical methods to quantify dietary fibre have evolved alongside the updated definitions. • The Association of Official Analytical Chemists (AOAC) method (2011.25) is considered the most reflective of the current Codex definition, capturing and enabling quantification of most dietary fibre entities, including total dietary fibre and its insoluble and soluble fractions by an enzymatic–gravimetric assay, and molecular weight by size exclusion chromatography or high- performance liquid chromatography. • Some food databases still include some fibre values derived from outdated AOAC methods that do not reflect current Codex fibre definitions. Nature reviews | GastroenteroloGy & HepatoloGy R e v i e w s in the upper gut, including decreasing gastric emptying rate and modulating small intestinal transit34. Increased luminal viscosity has been suggested to play a part in major regulatory effects of dietary fibre consumption, including delaying digestion, decreasing postprandial glycaemia35 and lipaemia36–38 and increasing satiety in humans39. The effect of the viscoelastic properties in the small intestine are less well defined, particularly as the effect of digestive secretions that dilute luminal contents are difficult to replicate and test in vivo. Indeed, a study investigating the effects of simulated gastric and small intestine digestion in vitro on the thickening abil- ity of six soluble fibres from different sources found substantial differences in their viscosity profiles. For example, xanthan gum retained viscosity more than all the other fibres40. Viscosity remains the accepted model for the cholesterol- lowering capacity of β- glucan. Increased luminal viscosity decreases diffusion of bile salts, preventing their resorption in the distal ileum41. Malabsorbed primary bile salts entering the colon can be de- conjugated by bacterial hydrolases to produce secondary bile acids, which have been shown to increase the risk of CRC through induction of epithelial cell hyperproliferation and increased oxidative DNA dam- age in vitro42. Although the mechanism remains unclear, as does the interaction between bile acids and dietary fibre43, this elevated CRC risk is not observed in vivo. Indeed there is substantial epidemiological evidence suggesting the opposite: that diets high in fibre are pro- tective against CRC in humans44. Additionally, in vitro studies have suggested that dietary fibres (for example, rice bran fibre, cellulose) might interact with digestive enzymes, inhibiting the rate of nutrient digestion27,45,46. An additional mechanism has been proposed, whereby an interaction between dietary fibres and the mucus layer results in localized increases in viscosity adjacent to the brush border in pigs47,48 regulating nutrient dif- fusion across it. In the colon, increases in luminal vis- cosity and water- holding capacity can in turn influence colonic bulk and transit time. The colonic contrac- tions moving luminal content between compartments might also reduce localized viscosity by shear thinning and alter colonic transit, particularly with fibres that are able to form disordered networks when hydrated (such as pectins). The consequences of these changes are likely to influence the extent of fermentation occur- ring in the colon, indeed with greater understanding of the physico chemical properties, it might be possible to affect microbiome composition49. There are several mathematical equations and mod- els, as well as rheological measurements to determine the viscosity of a solution. While the two most common analytical techniques of rheometry (measures the flow of a fluid) and viscometry (measures the viscosity of a fluid) are effective at determining viscosity of isolated Digested Cooked starches Cell wallStarch granules Soluble fibres • Pectin • β-Glucan • Galactomannan Insoluble fibres • Cellulose • Hemicellulose • Lignin Gelatinized (soluble) Resistant starch • RS-1: whole or partially milled • RS-2: granules (high amylose) • RS-3: retrograded (cooked and cooled) • RS-4: chemically modified • RS-5: starch–lipid complexes Raw starches Ungelatinized (insoluble) Fig. 1 | physicochemical characteristics of dietary fibre and their location within the plant cell. Polysaccharides that contribute to the dietary fibre definition can be divided into two broad categories: non- starch polysaccharides that are a main component of plant cell walls, and resistant starch (RS), the plant’s energy store and a major carbohydrate source in the human diet. Their chemical structure, interactions with other cell wall components, food processing and digestion can all influence their solubility, viscosity and fermentability. www.nature.com/nrgastro R e v i e w s fibre solutions, their validity in vivo remains equivocal as intestinal luminal contents are extremely heterogeneous and the effect of muscular contractions, peristalsis and mixing in the gastrointestinal tract cannot be replicated in vitro. Fibre fermentability. Observational studies have con- sistently shown differences in faecal microbiota com- position between industrialized and rural populations. These differences have been attributed to differences in the typical westernized diet consisting of foods that are highly refined and low in dietary fibre, particularly fermentable fibre50–55. Unlike mammalian cells, some species of the gut microbiota possess enzymes able to hydrolyse the chemical bonds within some dietary fibres within plant- based foods56. Interestingly, a number of specialist primarydegraders known as ‘keystone species’ have been identified within the large intestine57. These species have a superior ability to degrade certain dietary fibres and release energy on which other bacterial com- munities depend. For example, Ruminococcus bromii has been shown to specifically degrade certain types of resistant starch57. Examples of fermentable fibres include inulin- type fructans, galacto- oligosaccharides and resistant starch (TaBle 1). All natural plant fibres have some degree of fermentability, even cellulose and lignin (low ferment- ability), with only synthesized fibres such as methyl- cellulose being completely non- fermentable58 (TaBle 1). Fibre fermentability has traditionally been assessed using in vitro fermentation models of the digestive tract. Although this technique provides valuable mechanistic insights into fermentation patterns and behaviour of dif- ferent dietary fibres, the findings are not always reflected in vivo. For example in vitro models have indicated that psyllium is moderately fermented, whereas in vivo studies have demonstrated that it is poorly fermented59. This discrepancy is probably because the dilution and high- speed mechanical blending that occurs in vitro destroys the gel network, artificially exposing the fibres to enzymatic degradation. In vivo methods of measur ing fibre fermentability include quantification of short- chain fatty acids (SCFAs) in stools and hydrogen breath test- ing, although these also have limited interpretability, and breath testing in particular is subject to limited reproducibility60. Advances in MRI have enabled meas- urement of colonic gas volumes in response to differ- ent fibres in humans61,62. Although still in its infancy in terms of quantifying fermentation, MRI overcomes many of the limitations of the other methods and can non- invasively and simultaneously assess the water con- tent of the small intestine, colonic volumes and colonic gas volume63. Greater intake of dietary fibre, particularly from foods high in the fermentable fibres, has been associ- ated with higher stool SCFA concentrations in adults64. SCFAs have a number of key roles in the gastrointestinal tract. Animal studies have shown that SCFAs affect gas- trointestinal motility by stimulating colonic contractile activity through increasing the number of excitatory cholinergic neurons65. SCFAs also have a mediatory role, bridging communication between the mucosal micro- biota and the mucosal immune system, with preclini- cal evidence suggesting notable anti- inflammatory and immunomodulatory effects with relevance to inflam- matory disorders of the gut66. For example, SCFAs can influence intestinal adaptive immune responses through direct regulation of the size and function of the regu- latory T cell pool, including proliferative capacity and gene expression in mice67. In animal studies, SCFAs have also been implicated in maintaining intestinal barrier integrity68 and regulating appetite via several mech- anisms including the stimulation of gluconeogenesis in the liver69. Furthermore, SCFAs indirectly maintain gastrointestinal homeostasis via the reduction in lumi- nal pH70, which could be important in preventing colonization and inhibiting growth of acid- sensitive enteropathogens (Fig. 2). Table 1 | physicochemical characteristics of common dietary fibres Fibre type Common sources physicochemical characteristicsa solubility Viscosity Fermentability Cellulose All green plant cell walls Insoluble Non- viscous Low Lignins All green plant cell walls Insoluble Non- viscous Low Arabinoxylans Wheat, psylliumb Low to medium Medium Highb β- Glucans Oat, barley, fungi Low to medium Medium to high High Galactomannans Guar gum, fenugreek Medium to high Medium to high High Pectins Fruits, vegetables, legumes High Medium to high High Inulin Cereals, fruits, vegetables Medium to high Low to high High Galacto- oligosaccharides Pulses (e.g. beans, peas, lentils) High Low High Dextrins Cereals (e.g. wheat dextrins) High Non- viscous to low High Alginate Seaweed High High Low Methylcellulose Synthesized High High Non- fermentable Resistant Starch RS-1 (physically inaccessible) Whole grains, legumes, raw fruits, vegetables Insoluble Non- viscous High RS-2 (starch conformation) Cereals, raw legumes, raw fruits, vegetables Low Non- viscous High RS-3 (retrograded) Cooking and cooling of any starch source Low Non- viscous to low High RS-4 (chemically modified) Synthesized (e.g. acylated starches) Low to high Low to medium High RS-5 (starch– lipid complex) Synthesized (e.g. amylose and stearic acid) Low Low Low aPhysicochemical characteristics are not distinct entities but represent a continuum or gradient, and will vary depending on botanical origin, chemical structure and molecular weight, or whether the fibres are isolated or part of the cell wall matrix (Fig. 1). bDue to their structural features, wheat and psyllium sources of arabinoxylans are considered of only low fermentability. Nature reviews | GastroenteroloGy & HepatoloGy R e v i e w s Many factors can affect the rate, site and extent of fibre fermentation, including the composition of the microbiota (degradation capacity) with different micro- organisms shown to preferentially metabolize different fibres71 and the availability of other substrates (that is, proteins that have escaped digestion)72. Nonetheless, the key factor influencing fibre fermentability is thought to be its physicochemical characteristics (for example, sol- ubility, viscosity, accessibility). This has been shown in an in vitro fermentation study using healthy human stool samples from three donors to investigate the effect of 15 dietary fibres on SCFA production. Despite marked inter- individual differences in gut microbiota composi- tion between donors, SCFA production (concentrations and proportions) from the different fibres was reproduc- ible between samples. More specifically, rhamnose pro- duced the highest proportion of propionate followed by galactomannans, whereas fructans and other α- glucans and β- glucans produced the highest proportion of butyrate73. The effect of fermentable fibres on SCFA produc- tion has been consistently shown in vitro74–77. By con- trast, interpretation of human interventional studies is somewhat limited given that approximately 95% of SCFAs are absorbed by colonocytes, and therefore fae- cal SCFA concentrations only represent ~5% of the total SCFAs produced. Thus, faecal SCFAs better reflect the dynamic processes of both SCFA production and SCFA absorption, the former being affected by fibre source, colonic transit time and the gut microbiota and the latter being greatly affected by colonic transit time78. Reducing fermentable fibre intake might reduce bac- terial diversity. Several animal studies have shown that gut microbiota deprived of fermentable fibres shift to degrading and extracting alternative energy from the glycoprotein- rich mucus layer that acts as a protec- tive and mechanical barrier to pathogens79,80. Indeed, reduced availability of fermentable fibres leads to a thinner mucus layer81–83, which in turn might compro- mise intestinal epithelial integrity and increase pathogen susceptibility. Reduced availability of fermentable fibres also causes a shift from a stable microbial intestinal environment to one that is temporarily or permanently altered, often characterized by reduced bacterial diver- sity and richness, a state that is commonly referred to as dysbiosis84. A dysbiotic intestinal environment is a com- mon feature of a number of gastrointestinal disorders; for example, decreases in abundance of bifidobacteria85,86 and Firmicutes87–89 have been commonly observed in cohorts of people with IBS and IBD, respectively. The food matrix. The nature of the food matrix in which a dietary fibre is delivered will markedlyinfluence the extent of its physiological function. More specifically, the particle size and integrity of the plant cell walls affects the dissolution of soluble fibre90. This process has the potential to substantially affect luminal viscosity and reduce the rate of fermentation. Furthermore, the Fibre ↑ Solubility ↓ pH ↑ Viscosity → ↓ Glucose and lipid absorption rate Bile acids ↓ Reabsorption ↑ Stool bulk Microbial growth Dendritic cell Immunomodulation Inhibit pathogens ↓ pH Supports tight junction integrityLarge fibre particles T cell SCFA • Acetate • Propionate • Butyrate Liver Ca2+ ↑ Colonic muscular contraction Large intestineSmall intestine Intestinal epithelial cell Iron Phytate ↓ Gluconeogenesis ↑ Water binding Fig. 2 | Mechanisms by which different dietary fibres affect the gastrointestinal tract. There are several mechanisms by which the physicochemical characteristics (solubility, viscosity and fermentability) of dietary fibre might affect its functional properties in the gastrointestinal tract including influencing glucose and lipid absorption, contributing to stool output (frequency, consistency and weight) and stimulating changes in microbial composition and metabolite production including the production of short- chain fatty acids (SCFAs). www.nature.com/nrgastro R e v i e w s cell wall integrity can also encapsulate the intracellular starch91, therefore reducing digestion by endogenous enzymes and increasing the substrate available for microbial fermentation (RS-1; Fig. 1). Particle size can influence fibre fermentation, although to date, the majority of research has been con- ducted in vitro, with limited translational research inves- tigating the effects in humans. Reduced particle size of fibres has been associated with increased SCFA concen- trations in an in vitro fermentation system with human faecal inoculum92, suggesting greater bacterial fermen- tation. This outcome is likely to have been due to the fact that smaller particles have a greater external surface area exposed to bacterial enzymes. Similarly, the physical act of chewing and grinding high- fibre foods can have a notable role in particle size kinetics by increasing surface area and total pore volume as well as structural modifi- cation. For example, reducing the particle size of coconut residue from 1,127 μm to 550 μm led to an increase in hydration properties, including water- holding, retention and swelling capacity93. Equally, in human studies, the physical and mechanical effects of large and/or coarse insoluble fibre particles on the colonic mucosa has been shown to stimulate the secretion of water and mucus into the lumen, contributing to stool output (that is, consistency and weight)94,95. Porosity determines the degree to which enzymes or bacteria can diffuse into particles, which can substan- tially influence the fermentability of a fibre. Low porosity of a food matrix can result from maintenance of cell wall structures in the small intestine and, therefore, inability of digestive enzymes to access intracellular starch, lead- ing to increased RS-1, as is the case, for example, with whole chickpeas17. Low porosity of a food matrix in the large intestine can also impede fermentative degradation in humans96. Dietary fibre preparations high in insoluble fibres such as cellulose are likely to have low porosity, whereas those high in soluble fibres such as pectin have high porosity, and these differences in the porosity of fibres contribute to differences in their fermentability (TaBle 1). Functional characteristics of fibre Micronutrient bioavailability. Dietary fibre can influ- ence nutrient bioavailability beyond merely limit- ing micronutrient accessibility within a food matrix. Cereals containing dietary fibre (such as wheat) are a vital source of non- haem iron; however, other cereal components (for example, bran fractions) contain con- comitant factors such as phytate that reduce absorption of iron, zinc and calcium97. Additionally, in wheat, the aleurone contains the majority of the iron, but is encap- sulated by the cell walls (predominantly dietary fibre)98. Studies have shown that micro- milling to disrupt these structures results in increased mineral bioavailability in vitro99. In contrast to iron, several studies in humans have shown that consumption of specific fibres, such as fructans100 and galacto- oligosaccharides101, could increase absorption of dietary calcium. Based on exper- imental findings, the proposed mechanism involves decreased colonic pH resulting from SCFA produc- tion, which in turn can increase calcium solubility, thereby increasing passive transport of calcium across the intestine. The influence of dietary fibre consumption on vita- min absorption remains unclear. Several studies have demonstrated that some fibres improve absorption of some water- soluble and fat- soluble vitamins102,103, whereas others have shown no effect104. For example, a study in African Americans has shown that fibre can enhance the net colonic bacterial biosynthesis of B vita- mins such as folate105, whereas other studies in women have shown increased faecal excretion of vitamins following dietary fibre consumption106. The variety of fibre sources with varying physico- chemical properties demonstrates that further work is required. Gut transit time. Abnormal whole- gut transit times are found in some gastrointestinal disorders, which some types of fibre could normalize. For example, evidence from animal models demonstrates that, as found in rats, fermentable fibres can indirectly modulate contractile activity via production of SCFAs107, whereas, as found in dogs, non- fermentable fibres might contribute to stool weight that increases colonic volume and, there- fore, stimulates contractility108. Indeed, a systematic review and meta- analysis in healthy populations found that transit time decreased in a dose- dependent man- ner by 0.78 h per additional 1 g per day of wheat fibre109. Additionally, wheat fibre particle size has been shown to influence stool output, whereby coarse wheat fibre resulted in higher stool weight (mean 219.4 g per day) than fine wheat fibre (199 g per day) in one study of 21 healthy humans110. In the 1970s and 1980s, studies measuring gut transit time using radio- opaque markers and scintigraphy showed that dietary fibre interventions reduce gut transit time in humans111–114. One study in healthy humans showed a decrease in transit time with wheat bran sup- plementation from 70 h to approximately 46 h (reF.115). Insoluble, poorly fermented fibres (for example, wheat bran) have a greater effect on reducing gut transit time in healthy individuals and to a lesser extent in those with constipation116 than fermentable fibres that do not remain physically intact throughout the colon. More recently, studies investigating the use of a wire- less motility capsule that measures, among other things, transit time have been reported. Transit times measured with this device correlate with those obtained using radio- opaque markers and scintigraphy117,118 and the device has been shown to provide a more practical and less invasive method for determining gastric emptying time and whole gut transit time. For example, one con- trolled crossover trial in healthy individuals with back- ground fibre intakes of 14–15 g per day who consumed an additional 9 g per day of wheat bran or a low- fibre control diet for 3 days found that whole- gut transit time and colonic transit time were lower in those receiving wheat bran supplementation than in those receiving the control diet (−8.9 h and −10.8 h, respectively)119. Stool forming. For a dietary fibre to exert effects on stool output (that is, frequency, consistency and weight), it must possess certain physical characteristics. Wheat bran Nature reviews | GastroenteroloGy & HepatoloGy R e v i e w s supplementationhas been shown to increase stool fre- quency from 1 per day to 1.5 per day115, although the type of bowel movement (complete or spontaneous) was not reported, whereas further studies in healthy humans have shown that supplementation with a cellulose– pectin combination120 or psyllium121 and high- fibre breakfast cereals122 increase stool frequency. Both soluble, viscous fibres and insoluble, non- viscous fibres can contribute to improvements in stool consistency and stool weight (bulk). Soluble, viscous fibres (for example, psyllium) with a high water- holding capacity that are resistant to fermentation and form a viscoelastic substance in the gastrointestinal tract, con- tribute to softening hard stool and increasing stool bulk, making them easier to pass123,124. These properties also assist with diarrhoea by firming loose stools and slow- ing transit time125–127. By contrast, insoluble, non- viscous fibres (for example, coarse wheat bran) can contribute to improvements in stool consistency and stool weight via the mechanical stimulation of the intestinal mucosa95,128. Previous studies in adults with self- reported constipa- tion have shown improvements in stool consistency with increased consumption of rye bread129 and fibre bread130. Theoretically, fermentable fibres might con- tribute, in part, to stool weight via increasing microbial mass, but the effect size is limited compared with that of non- fermentable fibres. For example, results from six trials showed that RS-2 supplementation increased stool weight (+38 g per day, 95% CI 23–53 g per day; P < 0.001) at doses ranging from +21.5 to +37 g per day3. A review of interventional trials investigating outcomes in healthy humans concluded that fermentability deter- mines the role of fibre in total stool weight, with less fermentable fibres from cereals contributing most to stool weight131. Microbial specificity (prebiotics). Some fermentable fibres are also classed as prebiotics, a term whose defi- nition has been updated to “a substrate that is selectively utilized by host microorganisms conferring a health benefit”132. Examples of prebiotic fibres include the inulin- type fibres and galacto- oligosaccharides. Prebiotic fibres are known for their rapid fermenta- tive capacity and subsequent release of SCFAs, in par- ticular acetate, but selectively stimulate the growth of only a specific range of genera and/or species (that is, Bifidobacterium and Lactobacillus)133–135. This selectiv- ity is due to specific gene clusters within the bacterial genome that dictate the saccharolytic enzymes they produce and their phenotypic ability to selectively metabolize the prebiotic substrate136,137. The first landmark study demonstrating the prebio- tic effect in eight healthy volunteers found that supple- mentation with 15 g per day of oligofructose or inulin increased luminal bifidobacterial levels by almost one log10 (reF.138). Subsequent research has demonstrated a dose- dependent effect on luminal Bifidobacterium levels of oligofructose121 and galacto- oligosaccharides139 sup- plementation. Published in 2018, a systematic review and meta- analysis of 64 randomized controlled trials (RCTs) in humans demonstrated that fibre, and in par- ticular fructans and galacto- oligosaccharides and other candidate prebiotic fibres, increases the abundance of Bifidobacterium and Lactobacillus species133. However, large inter- individual variability in gut microbiota responses to dietary fibre have been reported140–144. A crossover RCT in 34 healthy partici- pants found that those with a habitually high dietary fibre intake had a greater gut microbial response to pre biotics (that is, increases in abundance of Bifidobacterium and Faecalibacterium, and decreases in Coprococcus, Dorea and Ruminococcus) compared with those with habitu- ally low dietary fibre intake, suggesting that individuals following a habitual high- fibre diet are more likely to benefit from an inulin- type fructan prebiotic145. Dietary fibre in gut disorders Given the substantial inter- condition and inter- individual variability in response to dietary fibre, there remains the complex challenge of unravelling which fibres are most appropriate for which gastrointestinal disorders. Consideration of the diverse physicochem- ical characteristics of fibre and how these translate to functional characteristics is fundamental to optimizing any clinical benefit (Fig. 3). Consideration should also be given to maintaining the balance between optimiz- ing symptom benefit (that is, management and main- tenance) and limiting symptom exacerbation (that is, tolerance). The manipulation of dietary fibre is a common approach in clinical practice for many gastro- intestinal disorders and is commonly recommended as first- line therapy in the management of several gastro- intestinal symptoms (TaBle 2), despite the limited num- ber of RCTs across gastrointestinal disorders, all of which used heterogeneous methodologies (for example, fibre type, amount, duration). Irritable bowel syndrome. IBS is a functional gastroin- testinal disorder characterized by recurrent abdominal pain and change in stool habit (that is, constipation, diar- rhoea or both), often alongside abdominal bloating and distension146. The mechanisms underpinning IBS symp- toms include visceral hypersensitivity, and alterations in gut–brain interactions, immune activation, gut motil- ity and the gut microbiota. Since the revised Rome IV criteria were introduced in 2016, estimated worldwide prevalence of IBS has decreased from 11.7% (Rome III) to 5.7% (Rome IV)147. Guidelines for fibre consumption in individuals with IBS vary. The National Institute for Health and Care Excellence8 in the UK recommends that resistant starch intake should be reduced, whereas the World Gastroenterology Organization Global Guidelines148 suggest that fibre- rich foods or fibre supplements (for example, psyllium) should be encouraged and that insolu ble fibres that might exacerbate symptoms should be limited. To date, a number of systematic reviews and meta- analyses have concluded that some fibres are beneficial in reducing IBS symptoms and improving stool frequency and consistency, although results are inconsistent with wide variation in responses149–151. Benefits seem to be limited to soluble fibre (RR of having continued symp- toms after supplementation 0.83, 95% CI 0.73–0.94)152, www.nature.com/nrgastro R e v i e w s compared with other fibres such as bran (RR 0.90, 95% CI 0.79–1.03). The ongoing changes in diagnostic cri- teria (for example, Rome Criteria for IBS), and lack of standardization in outcome measures between studies presents major challenges when attempting to com- pare findings of previous studies. Further rigorous and long- term RCTs are required, and there is an urgent need to assess the different functionalities of dietary fibres in subgroups of individuals with IBS (for exam- ple, specifically those with constipation- predominant IBS or diarrhoea- predominant IBS) to enable a better understanding of its therapeutic potential. Interestingly, a three- period, crossover mechanistic study revealed that despite similar physiological responses to prebio- tics between patients with IBS and healthy individuals as controls, only those with IBS experienced symptoms when challenged with 40 g of fructose or inulin whereas the healthy controls did not, suggesting that visceral hypersensitivity to colonic gas is involved in the induc- tion of symptoms, rather than excessive gas production per se153. A limited number of clinical trials investigating prebiotic supplementation (for example, oligofructose, fructo- oligosaccharide and β- galacto- oligosaccharides) ranging from 3.5 g per day to 20 g per day over 4–12 weeks have been conducted in IBS populations, with mixed results154–157. A systematic review and meta- analysis pub- lished in 2019 of 11 RCTsincluding 729 patients showed that although the abundance of bifidobacteria increased following prebiotic supplementation, there were no differences in response rates, or severity of abdominal pain, bloating, flatulence or quality of life158. Notably, subgroup analysis showed improvement in flatulence with lower prebiotic doses (≤6 g per day; standardized mean difference (SMD) −0.35, 95% CI −0.71 to 0.00; P = 0.05) and non- inulin- type fructans (for example, galacto- oligosaccharide, guar gum: SMD −0.34, 95% CI −0.66 to −0.01; P = 0.04). Although little current evidence exists for the use of prebiotics in IBS management158,159, emerging evidence suggests that second- generation can- didate prebiotics such as pectin and partially hydrolysed guar gum have bifidogenic properties160 with potential therapeutic use in IBS161, possibly due to their viscosity characteristics and, therefore, slower fermentation rate. Inflammatory bowel disease. IBD encompasses Crohn’s disease and ulcerative colitis, both chronic, relapsing gastrointestinal disorders of which the pathogenesis remains incompletely understood, although a dysreg- ulated mucosal inflammatory response in genetically susceptible individuals is responsible for the initiation and maintenance of IBD162. This process involves altera- tions in immunological factors (for example, T and B cell regulation) and microbial factors (for example, diversity and functionality of bacteria such as Faecalibacterium prausnitzii)163. The prevalence of IBD exceeds 0.3% across North America, Oceania and Europe164. The goal of IBD treatment is to halt disease progression, main- tain remission and prevent recurrence of inflammatory episodes. There continues to be debate on the clinical benefits of dietary fibre in IBD165 despite plausible mechanisms for its therapeutic potential, including the production of SCFAs (particularly butyrate) that could attenuate intes- tinal inflammation through upregulation or downregu- lation of cytokine expression (for example, IL-10, IFNγ ↑ V is co si ty ↑ Solubility ↑ F er me nt ab ilit y Physicochemical • Soluble • Non-viscous • Fermentable • e.g. Inulin, GOS Functional • SCFA production • Prebiotic Physicochemical • Soluble • Viscous • Fermentable • e.g. Pectin, galactomannan Functional • Nutrient bioavailability • SCFA production Physicochemical • Medium solubility • Medium viscosity • Low fermentability • e.g. Psyllium Functional • Nutrient bioavailability • Faster transit • Water holding Physicochemical • Insoluble • Non-viscous • Non-fermentable • e.g. Cellulose in wheat bran Functional • Faster transit • Stool bulking Fig. 3 | spectrum of physicochemical characteristics of dietary fibre. The physicochemical characteristics of fibre (solubility, viscosity and fermentability) form a continuum and work in concert to determine its functional properties in the gastrointestinal tract. The combination of these three physicochemical characteristics determines the functional effects of fibres in the gut. For example, fibres in the left- hand, bottom, near corner (insoluble, non- viscous, non- fermentable) have functions relating to gut transit time; fibres in the right- hand, bottom, far corner (soluble, non- viscous, fermentable) have functions relating to microbiome and fermentation; and fibres in the right- hand, top, far corner (soluble, viscous, fermentable) have functions relating to microbiome, fermentation and nutrient bioavailability. Fibres in intermediate positions would be predicted to have intermediate functional properties. GOS, galacto- oligosaccharides; SCFA, short- chain fatty acid. Nature reviews | GastroenteroloGy & HepatoloGy R e v i e w s and IL-1β) by colonic epithelial cells according to in vitro data67,166,167. A number of studies have found alterations in the gut microbiota (for example, reduced abundance of Bifidobacterium and Faecalibacterium prausnitzii) in patients with Crohn’s disease that might be amenable to prebiotic fibre supplementation168,169. Previous studies have generally found lower stool SCFA concentrations in patients with IBD than in healthy individuals170–172, suggesting a reduced fermentative capacity and an impairment in SCFA production in this patient group. Collectively, it is conceivable that fibre (dietary or sup- plement form) might prevent IBD, maintain or restore intestinal epithelial integrity in IBD, although studies in humans of fibre in the prevention, maintenance and treatment of IBD are extremely limited165. In terms of the risk of developing IBD, a prospective cohort study in 170,776 women in the Nurses’ Health Cohort Study followed up over 26 years identified 269 and 338 cases of Crohn’s disease and ulcerative colitis, respectively173. Compared with women with the lowest energy- adjusted dietary fibre intake, intake in the high- est quintile (median of 24.3 g per day) was associated with a 40% reduction in risk of Crohn’s disease (hazard ratio for Crohn’s disease, 0.59, 95% CI 0.39–0.90), but not ulcerative colitis173. On the contrary, a meta- analysis of 14 case–control studies found an association between higher intakes of vegetables and lower risk of ulcerative colitis (OR 0.71, 95% CI 0.58–0.88), but not Crohn’s disease (OR 0.66, 95% CI 0.40–1.09), whereas a higher consumption of fruit was associated with lower risk of both ulcerative colitis (OR 0.69, 95% CI 0.49–0.96) and Crohn’s disease (OR 0.57, 95% CI 0.44–0.74)174. However, a large prospective study including 401,326 participants recruited from across eight European coun- tries found no associations between intakes of total fibre or fibre from specific sources and the development of IBD175; however, this study was in a population of peo- ple recruited in their middle age, beyond the age at which IBD commonly develops (mean age at recruit- ment 49.6–51.6 years, range 20–80 years). Furthermore, given the nature of these observational studies, recall bias is likely. Only a limited number of clinical trials investigating the use of fibre in the maintenance and treatment of IBD have been undertaken, and they have been summarized in a systematic review165. For maintenance of remission, of the four studies included in patients with ulcerative colitis (n = 213), two found positive effects on disease activity: one larger RCT found continued remission at 12 months across all groups (psyllium versus mesalamine Table 2 | Guidelines and recommendations for the use of fibre in gastrointestinal disorders Gastrointestinal disorder Dietary fibre recommendations level of evidence IBS- C Soluble fibre in supplement form (e.g. psyllium, methylcellulose, partially hydrolysed guar gum)8,12,148–150 Meta- analyses of RCTs Adjust fibre intake according to symptoms including adding naturally occurring sources (e.g. oats or linseeds)8 Professional consensus Ground linseeds (6–24 g per day); increase gradually over a 3- month period9 Small number of RCTs IBS- D Reduce intake of insoluble fibre, such as wholemeal or high- fibre flour and breads, cereals high in bran, and whole grains such as brown rice8 Systematic review of RCTs Soluble fibre in supplement form (e.g. psyllium)148,150,204 Meta- analyses of RCTs Adjust fibre intake according to symptoms8 Professional consensus Inflammatory bowel disease Encourage a varied diet to meet energy and nutrient requirements, including dietary fibre, including a wide variety of fruit and vegetables, cereals, grains, nuts and seeds10 Professional consensus Consider limiting fibre and fibrous foods in patients with strictures12 Professional consensus Dietary fibre should not be restricted, unless intestinal obstruction12 Professional consensus Ulcerative colitis might be more amenable to fibre supplement interventions than Crohn’s disease165 Systematic review of RCTs Diverticular disease Low- fibre diet during active diverticulitis to ‘minimize irritation’12Professional consensus High- fibre diet from mixed sources to prevent diverticulitis Observational studies and professional consensus Functional constipation Encourage gradual increases (weeks rather than days) in fibre (or by adding fibre supplements) to minimize gastrointestinal discomfort including bloating and flatulence aiming for 20–30 g per day, being aware that beneficial effects might be seen after several weeks12,13 Meta- analyses of RCTs Encourage whole- fibre foods with additional components with laxating effects (e.g. sorbitol) such as prunes or apricots13 Small number of RCTs and professional consensus High- dose psyllium (>15 g/day)124 Meta- analysis of RCTs Guidelines are based upon research and professional consensus, but frequently the evidence is not from high- quality clinical trials. IBS- C, irritable bowel syndrome with constipation; IBS- D, irritable bowel syndrome with diarrhoea; RCTs, randomized controlled trials. www.nature.com/nrgastro R e v i e w s versus psyllium plus mesalamine), whereas a smaller unblinded RCT found a lower rate of treatment failure at 12 months for psyllium plus mesalamine (28%) ver- sus mesalamine alone (35%). Four studies in patients with Crohn’s disease (n = 465) found equivalence in the number of patients with deteriorating disease at 24 months between the high- fibre group (mean intake 27 g per day) and the low- fibre group (mean intake 15 g per day), one study found negative outcomes in patients consuming a high- fibre diet (33.4 ± 1.8 g per day, of which 2.9 ± 0.3 g per day was from raw fruit and vegeta- bles) with markedly higher treatment failure and shorter time to relapse (1.4 versus 2.8 months) than patients consuming a low- fibre exclusion diet165. By contrast, an observational cohort study in 1,619 patients with IBD found that a higher fibre intake was associated with reduced risk of flare in those with Crohn’s disease (adjusted OR 0.58, 95% CI 0.37–0.90), but not in those with ulcerative colitis (adjusted OR 1.82, 95% CI 0.92– 3.60), although intakes were measured using a 26- item self- reported, retrospective dietary survey176. For treat- ment of active disease, the systematic review included five trials in patients with ulcerative colitis (n = 114) and showed positive effects of fibre (for example, germinated barley, combined oligofructose–inulin) on disease activ- ity. Although five trials in patients with Crohn’s disease (n = 193) showed no positive effect of fibre, three studies showed equivalent effects of a high- fibre diet compared with another dietary intervention in cohorts with active, inactive or mixed disease stages165. Collectively, based on these results, although there is limited evidence for the value of dietary fibre in the maintenance or treatment of IBD, dietary fibre should not be unnecessarily restricted in patients with IBD, unless intestinal strictures are present and there is risk of obstruction. Overall, the results suggest that ulcerative colitis might be more amenable to dietary fibre inter- ventions than Crohn’s disease, potentially due to the formation of SCFAs at the site of disease165. Historically, it has been common in clinical practice to recommend reducing high- fibre foods during relapse, although this practice is not evidence- based, and patients should be monitored in regard to their tolerance to fibre during both remission and relapse. Diverticular disease. Diverticular disease refers to herniation of the mucosa and submucosa through the muscular layer of the colonic wall177. The pathogenesis of diverticular disease relates to colonic smooth muscle overactivity, thickening of the colonic wall and/or genet- ics, in addition to lifestyle factors such as fibre intake and physical activity, although associations remain inconsistent178. The incidence of diverticular disease is highest in economically developed countries with cases continuing to increase, and is strongly associated with age, with a prevalence of 5% in those under 40 years and up to 65% in those over 65 years179. Although the majority of patients with diverticular disease remain asymptomatic (~80%), inflammation of a diverticulum presents as diverticulitis that can vary in duration and severity, but can be complicated by fistulae, abscesses, obstruction and perforation180. A prospective cohort study in 46,295 men investigat- ing the risk of developing diverticular disease, found a positive association between a Western dietary pattern and an increased risk of diverticulitis, in particular, a higher consumption of red meat and lower consump- tion of dietary fibre181. Similar results were found in the Million Women Study including 690,075 women in the UK whereby the relative risk of diverticular disease for a 5 g per day greater fibre intake was 0.86 (95% CI 0.84–0.88). Notably, the source of fibre seemed to influ- ence disease risk whereby an additional 5 g per day of fibre from fruit (RR 0.81, 95% CI 0.77–0.86; P < 0.01) or cereals (RR 0.84, 95% CI 0.81–0.88; P < 0.01) was associ- ated with significant reductions in risk, an additional 5 g per day of fibre from vegetables was not associated with risk (RR 1.03, 95% CI 0.93–1.14; P = 0.634) whereas an additional 1 g per day of fibre from potatoes was asso- ciated with a greater risk (RR 1.04, 95% CI 1.02–1.07; P = 0.002)182. By contrast, one observational case–control study in 2,104 participants undergoing colonoscopy found that a high- fibre diet was not protective against diverticular disease183; in fact, those with the highest quartile of fibre intake showed an increased prevalence of diverticular disease (prevalence ratio 1.30, 95% CI 1.13–1.50). However, it is important to note that dietary intake was measured up to 12 weeks following colon- oscopy and it is not possible to exclude alterations in diet as a consequence, rather than a cause, of the diverticular disease diagnosis. Overall, a meta- analysis of five pro- spective cohort studies (19,282 cases, 865,829 partici- pants) found a reduced risk of diverticular disease, with a relative risk of 0.74 (95% CI 0.71–0.78) for every addi- tional 10 g per day of total fibre intake184. Again, the level of protection varied with the fibre source, with an addi- tional 10 g per day of fibre from fruit providing the great- est protection (RR 0.56, 95% CI 0.37–0.84), followed by cereals (RR 0.74, 95% CI 0.67–0.81) and vegetables (RR 0.80, 95% CI 0.45–1.44)184. The proposed mechanisms by which fibre reduces the risk of diverticular disease include increased stool bulk, decreased colonic pressure and therefore reduced herniation. In terms of fibre being used in the management of acute diverticulitis, there is no consensus on fibre intake. Some guidelines suggest a low- fibre diet to ‘minimize irritation’12 and a gradual increase to 20–30 g per day through diet or as fibre supplements once inflammation has resolved185. These recommendations are often used in clinical practice, although they are based on physio- logical rationale or uncontrolled studies, and not robust clinical trials. A systematic review published in 2018 rec- ommended that patients with uncomplicated diverticu- litis should be placed on a liberalized diet (for example, solid food, no bowel rest or nil by mouth), as opposed to dietary restrictions, and a high- fibre diet that meets individualized nutrient requirements, with or without fibre supplementation. However, it was recognized that recommendations were based on a limited number of low- quality studies186. In terms of fibre being used in the management of uncomplicated diverticular disease, a systematic review from 2012 (reF.187) found only three RCTs of sufficient quality, although they yielded inconsistent Nature reviews | GastroenteroloGy & HepatoloGy R e v i e w s findings188–190. In 2019, a systematic review of nine con- trolled or uncontrolled trials in patients with asymp- tomatic orsymptomatic uncomplicated diverticular disease identified only one study investigating the effect of a high- fibre diet with bran on the risk of developing diverticulitis, but this study did not have a control group against which to compare the risk191. In the remaining studies, fibre supplementation improved stool weight (mean difference, MD, +42 g per day; P < 0.00001) but did not affect gastrointestinal symptoms (SMD −0.13; P = 0.16) or gut transit time (MD −3.70; P = 0.32)191. Overall, in those with diverticular disease there is lim- ited evidence for an effect of fibre in preventing acute diverticulitis. Functional constipation. Functional constipation is one of the most common functional bowel disorders and is characterized by symptoms of difficult or infre- quent stool passage, or incomplete defaecation, with- out structural cause146. Unlike IBS in which abdominal pain must be present, functional constipation does not have abdominal pain as a predominant symptom, and although not considered to be a serious condition, it can lead to complications such as faecal impaction, bowel perforation and haemorrhoids146, and the symp- toms experienced are varied and place a burden on the patient192. At present, there are limited data available on the pathophysiology of functional constipation, although lifestyle factors, including low fibre intake and low levels of physical activity are associated with the presence of constipation and may play a role in its aetiology192. The majority of studies have focused on chronic constipa- tion, the estimated global prevalence of which is 14%123, although variations in symptoms used in self- reporting constipation result in varying numbers presenting to their doctor193. A number of large cohort studies have shown positive associations between high intakes of dietary fibre and stool frequency194,195. A systematic review and meta- analysis of seven RCTs concluded that fibre is effective in treating chronic constipation in adults compared with placebo. For example, fibre (dietary; for example, wheat bran) and in supplement form (for example, psyllium) including prebiotics (for example, inulin) was associated with increased stool frequency (SMD 0.39, 95% CI 0.03–0.76; P = 0.03) and more normalized stool consistency (SMD 0.35, 95% CI 0.04–0.65; P = 0.02). In particular, subgroup analysis suggested that a high dose (>15 g per day) of psyllium was the most effective in increasing stool frequency and improving stool consistency124. However, fibre can induce other gastrointestinal symptoms such as flatulence (compared with placebo: SMD 0.56, 95% CI 0.12–1.00; P = 0.01). This meta- analysis further highlights the importance of choosing fibres with the most appropriate physicochemical characteristics to provide the preferred functional benefit. For exam- ple, non- viscous, highly fermentable fibres such as prebiotic fibres (inulin and galacto- oligosaccharides) did not consistently have any benefit over placebo in increasing stool frequency and stool consistency. This is because these fibres are almost completely fermented in the colon so that and their water‐holding capacity is lost. By contrast, viscous and poorly fermented fibres such as psyllium retain their physicochemical charac- teristics (such as high- water holding and gel- forming capacity) throughout the gastrointestinal tract59. Indeed, although insoluble fibres containing large and/or coarse particles can provide a regulatory benefit94,196, there are fibres (wheat dextrin and finely ground wheat bran) that have been shown to contribute only to the dry mass of stool, resulting in decreased stool water content and a constipating effect, potentially exacerbating symptoms in those with constipation197. This finding might, in part, explain the disparities in the findings of previous studies showing laxative effects of insoluble fibre198. The effect of different quantities of different fibres on health have been previously highlighted3. One review that summarized the research of Burkitt, who advocated the intake of >50 g per day of dietary fibre for preven- tion of chronic disease (for example, colon cancer)199, noted that fibre intakes of >35 g per day seem to be more effective in reducing chronic disease than lower intakes. Moreover, it has been suggested that the mini- mal effects of fibre supplementation on health outcomes shown in many of the intervention trials in humans to date could simply reflect the insufficient quantity of fibre supplement provided in these studies199. Future research Fibre co- administration. Currently, extracted and isolated fibres (such as inulin or psyllium) from vari- ous sources are commonly added to food products to enrich the fibre content, in order to assist people in achieving the dietary recommendations for dietary fibre. It is plausible that co- administration of different fibres (for example, combined isolated fibres) might provide a ‘dual treatment’ by driving different func- tionalities that target separate gastrointestinal features (that its, the correction of dysbiosis, and normalization of stool form and transit time), potentially maximizing the effect of clinically meaningful symptom improve- ment. Yet, to date, there is limited research in the area of co- administration. A 3- week randomized crossover block design study in 19 healthy volunteers found that wheat bran plus resistant starch (12 g per day and 22 g per day, respectively) produced greater benefits (such as increased stool output, reduced transit time, reduced faecal pH (a proxy for luminal pH, for which lower values are associated with the suppression of potentially pathogenic microorganisms), and increased concentra- tions of acetate and butyrate) than wheat bran (12 g per day) alone200. Furthermore, a study in animals demon- strated that wheat bran combined with resistant starch versus wheat bran alone can shift fermentation distally, thus potentially improving the luminal environment and providing protective effects further along the colon201. In addition, an in vitro study using faecal microbiota from healthy donors to compare degradation profiles of single fibres (arabinoxylan, chondroitin sulfate, galac- tomannan, polygalacturonic acid, xyloglucan) versus a combination of these showed slower utilization of some soluble dietary fibres when present in a mixture, www.nature.com/nrgastro R e v i e w s suggesting that this strategy could be used as a means of delivering fibres to the more distal regions of the colon202. Further research is required to determine whether fibre combinations might be efficacious in the management of gastrointestinal and other disorders. As our under- standing of the physicochemical characteristics of dietary fibre advances, co- administration of known fibres with different functional characteristics is likely to offer greater therapeutic utility. Natural fibres. Natural sources of dietary fibre are increasingly used as they often contain many differ- ent fibres. For this reason, they might hold some of the benefits of co- administration, have synergistic effects and offer diverse functional characteristics that could offer therapeutic potential in the management of a range of gastrointestinal disorders. Examples of novel plant- based fibres include prickly pear, galactoman- nan, plantain peel, ivy gourd, Gnetum africanum, yacon root, Moringa oleifera, which have unique combinations of different fibres and are rich sources of other bioac- tive compounds, such as polyphenols, that have poten- tial anti- inflammatory and antibacterial properties203. However, there are a limited number of studies of natural fibres in the management of gastrointestinal disorders. Conclusions Manipulating and/or increasing fibre intake is a promising therapeutic strategy in the prevention and management of many gastrointestinal disorders. Physicochemical characteristicssuch as solubility, viscosity and fermen- tability drive different functionalities in the gastro- intestinal tract, and therefore underpin their therapeutic potential. Current guidelines and recommendations reflect earlier studies that have used a wide range of die- tary fibres with different physicochemical and functional characteristics. The lack of consistency and reporting of these characteristics in studies to date has limited the clinical utility of dietary fibre for managing gastrointes- tinal disorders. There is an urgent need for well- designed RCTs to determine which physicochemical character- istics, and therefore which fibre sources, and in what doses and durations are optimal for clinically mean- ingful gastrointestinal health benefits. 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