Consistent Prebiotic Effect on Gut Microbiota With Altered FODMAP Intake in Patients with Crohn's Disease: A Randomised, Controlled Cross-Over Trial of Well-Defined Diets.

OBJECTIVES: Altering FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) intake has substantial effects on gut microbiota. This study aimed to investigate effects of altering FODMAP intake on markers of colonic health in patients with Crohn's disease. METHODS: After evaluation of their habitual diet, 9 patients with clinically quiescent Crohn's disease were randomised to 21 days of provided low or typical ("Australian") FODMAP diets with ≥21-day washout in between. Five-day fecal samples were collected at the end of each diet and analyzed for calprotectin, pH, short-chain fatty acids (SCFA) and bacterial abundance. Gastrointestinal symptoms were recorded daily. RESULTS: Eight participants collected feces and were adherent to the diets. FODMAP intake differed across the three dietary periods with low

Adherence to the gluten-free diet can achieve the therapeutic goals in almost all patients with coeliac disease: A 5-year longitudinal study from diagnosis.

BACKGROUND: Key aims of treatment of coeliac disease are to heal the intestinal mucosa and correct nutritional abnormalities. AIM: We aim to determine prospectively the degree of success and time course of achieving those goals with a gluten-free diet. METHODS: Ninety-nine patients were enrolled at diagnosis and taught the diet. The first 52 were reassessed at 1 year and 46 at 5 years, 25 being assessed at the three time points regarding dietary compliance (dietitian-assessed), coeliac serology, bone mineral density and body composition analysis by dual energy X-ray absorptiometry, and intestinal histology. RESULTS: Mean age (range) was 40 (18-71) years and 48 (76%) were female. Dietary compliance was very good to excellent in all but one. Tissue transglutaminase IgA was persistently elevated in 44% at 1 year and 30% at 5 years and were poorly predictive of mucosal disease. Rates of mucosal remission (Marsh 0) and response (Marsh 0/1) were 37% and 54%, and 50% and 85% at 1 and 5 years, respectively. Fat mass increased significantly over the first year in those with normal/reduced body mass index. Lean body mass indices more slowly improved irrespective of status at diagnosis with significant improvement at 5 years. Bone mass increased only in those with osteopenia or osteoporosis, mostly in year 1. CONCLUSION: Dietary compliance is associated with a high chance of healing the intestinal lesion and correction of specific body compositional abnormalities. The time course differed with body fat improving within 1 year, and correction of the mucosal lesion and improvement in lean mass and bone mass taking longer.

Diets that differ in their FODMAP content alter the colonic luminal microenvironment.

OBJECTIVE: A low FODMAP (Fermentable Oligosaccharides, Disaccharides, Monosaccharides And Polyols) diet reduces symptoms of IBS, but reduction of potential prebiotic and fermentative effects might adversely affect the colonic microenvironment. The effects of a low FODMAP diet with a typical Australian diet on biomarkers of colonic health were compared in a single-blinded, randomised, cross-over trial. DESIGN: Twenty-seven IBS and six healthy subjects were randomly allocated one of two 21-day provided diets, differing only in FODMAP content (mean (95% CI) low 3.05 (1.86 to 4.25) g/day vs Australian 23.7 (16.9 to 30.6) g/day), and then crossed over to the other diet with ≥21-day washout period. Faeces passed over a 5-day run-in on their habitual diet and from day 17 to day 21 of the interventional diets were pooled, and pH, short-chain fatty acid concentrations and bacterial abundance and diversity were assessed. RESULTS: Faecal indices were similar in IBS and healthy subjects during habitual diets. The low FODMAP diet was associated with higher faecal pH (7.37 (7.23 to 7.51) vs. 7.16 (7.02 to 7.30); p=0.001), similar short-chain fatty acid concentrations, greater microbial diversity and reduced total bacterial abundance (9.63 (9.53 to 9.73) vs. 9.83 (9.72 to 9.93) log10 copies/g; p<0.001) compared with the Australian diet. To indicate direction of change, in comparison with the habitual diet the low FODMAP diet reduced total bacterial abundance and the typical Australian diet increased relative abundance for butyrate-producing Clostridium cluster XIVa (median ratio 6.62; p<0.001) and mucus-associated Akkermansia muciniphila (19.3; p<0.001), and reduced Ruminococcus torques. CONCLUSIONS: Diets differing in FODMAP content have marked effects on gut microbiota composition. The implications of long-term reduction of intake of FODMAPs require elucidation. TRIAL REGISTRATION NUMBER: ACTRN12612001185853.

The role of FODMAPs in irritable bowel syndrome.

PURPOSE OF REVIEW: Irritable bowel syndrome (IBS) is a condition affecting approximately 10-15% of Western populations. The Rome III criteria are applied to many studies to validate the diagnosis of IBS. The low fermentable oligo, di, monosaccharides and polyol (FODMAP) diet has been the subject of many robust clinical trials and is now used as the primary dietary therapy internationally. This review examines the current evidence for the role of the low FODMAP diet in IBS. RECENT FINDINGS: Detailed commentary on original research involving FODMAPs and IBS symptoms from 2013 to 2014 is provided. SUMMARY: The low FODMAP diet has been shown to be an efficacious therapy for reduction of functional gastrointestinal symptoms seen in IBS. Recent publications provide randomized controlled trial and prospective observational evidence in support of the diet for symptom management. The low FODMAP diet appears to be superior to a gluten-free diet in people with self-reported nonceliac gluten sensitivity. Although the low FODMAP diet has not been shown to reduce the prebiotic effect in the colon, total colonic bacterial load was reduced. Further research investigating the potential health implications of both this and the nutritional adequacy of the liberalized low FODMAP diet is required.

Characterization of Adults With a Self-Diagnosis of Nonceliac Gluten Sensitivity.

Background: Nonceliac gluten sensitivity (NCGS), occurring in patients without celiac disease yet whose gastrointestinal symptoms improve on a gluten-free diet (GFD), is largely a self-reported diagnosis and would appear to be very common. The aims of this study were to characterize patients who believe they have NCGS. Materials and Methods: Advertising was directed toward adults who believed they had NCGS and were willing to participate in a clinical trial. Respondents were asked to complete a questionnaire about symptoms, diet, and celiac investigation. Results: Of 248 respondents, 147 completed the survey. Mean age was 43.5 years, and 130 were women. Seventy-two percent did not meet the description of NCGS due to inadequate exclusion of celiac disease (62%), uncontrolled symptoms despite gluten restriction (24%), and not following a GFD (27%), alone or in combination. The GFD was self-initiated in 44% of respondents; in other respondents it was prescribed by alternative health professionals (21%), dietitians (19%), and general practitioners (16%). No celiac investigations had been performed in 15% of respondents. Of 75 respondents who had duodenal biopsies, 29% had no or inadequate gluten intake at the time of endoscopy. Inadequate celiac investigation was common if the GFD was initiated by self (69%), alternative health professionals (70%), general practitioners (46%), or dietitians (43%). In 40 respondents who fulfilled the criteria for NCGS, their knowledge of and adherence to the GFD were excellent, and 65% identified other food intolerances. Conclusions: Just over 1 in 4 respondents self-reporting as NCGS fulfill criteria for its diagnosis. Initiation of a GFD without adequate exclusion of celiac disease is common. In 1 of 4 respondents, symptoms are poorly controlled despite gluten avoidance.

A diet low in FODMAPs reduces symptoms of irritable bowel syndrome.

BACKGROUND & AIMS: A diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) often is used to manage functional gastrointestinal symptoms in patients with irritable bowel syndrome (IBS), yet there is limited evidence of its efficacy, compared with a normal Western diet. We investigated the effects of a diet low in FODMAPs compared with an Australian diet, in a randomized, controlled, single-blind, cross-over trial of patients with IBS. METHODS: In a study of 30 patients with IBS and 8 healthy individuals (controls, matched for demographics and diet), we collected dietary data from subjects for 1 habitual week. Participants then randomly were assigned to groups that received 21 days of either a diet low in FODMAPs or a typical Australian diet, followed by a washout period of at least 21 days, before crossing over to the alternate diet. Daily symptoms were rated using a 0- to 100-mm visual analogue scale. Almost all food was provided during the interventional diet periods, with a goal of less than 0.5 g intake of FODMAPs per meal for the low-FODMAP diet. All stools were collected from days 17-21 and assessed for frequency, weight, water content, and King's Stool Chart rating. RESULTS: Subjects with IBS had lower overall gastrointestinal symptom scores (22.8; 95% confidence interval, 16.7-28.8 mm) while on a diet low in FODMAPs, compared with the Australian diet (44.9; 95% confidence interval, 36.6-53.1 mm; P < .001) and the subjects' habitual diet. Bloating, pain, and passage of wind also were reduced while IBS patients were on the low-FODMAP diet. Symptoms were minimal and unaltered by either diet among controls. Patients of all IBS subtypes had greater satisfaction with stool consistency while on the low-FODMAP diet, but diarrhea-predominant IBS was the only subtype with altered fecal frequency and King's Stool Chart scores. CONCLUSIONS: In a controlled, cross-over study of patients with IBS, a diet low in FODMAPs effectively reduced functional gastrointestinal symptoms. This high-quality evidence supports its use as a first-line therapy. CLINICAL TRIAL NUMBER: ACTRN12612001185853.

Short-chain carbohydrates and functional gastrointestinal disorders.

Carbohydrates occur across a range of foods regularly consumed including grains such as wheat and rye, vegetables, fruits, and legumes. Short-chain carbohydrates with chains of up to 10 sugars vary in their digestibility and subsequent absorption. Those that are poorly absorbed exert osmotic effects in the intestinal lumen increasing its water volume, and are rapidly fermented by bacteria with consequent gas production. These two effects alone may underlie most of the induction of gastrointestinal symptoms after they are ingested in moderate amounts via luminal distension in patients with visceral hypersensitivity. This has been the basis of the use of lactose-free diets in those with lactose malabsorption and of fructose-reduced diets for fructose malabsorption. However, application of such dietary approaches in patients with functional bowel disorders has been restricted to observational studies with uncertain efficacy. As all dietary poorly absorbed short-chain carbohydrates have similar and additive effects in the intestine, a concept has been developed to regard them collectively as FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) and to evaluate a dietary approach that restricts them all. In patients with irritable bowel syndrome, there is now an accumulating body of evidence, based on observational and comparative studies, and on randomized-controlled trials that supports the notion that FODMAPs trigger gastrointestinal symptoms in patients with functional bowel disorders, and that a diet low in FODMAPs offers considerable symptom relief in the majority of patients who use it.

Design of clinical trials evaluating dietary interventions in patients with functional gastrointestinal disorders.

Clear guiding principles for the design and conduct of dietary intervention trials in functional gastrointestinal disorders (FGID) are lacking. This narrative review examines the specific challenges associated with the design and reporting in dietary intervention trials. Dietary intervention trials need to address the collinearity between food, nutrients, and bioactive components that obscure the relationship between food and their effects in the gut. Randomized, double-blinded, placebo-controlled studies remain the gold standard for dietary trials, but are limited by difficulties in adequate masking of study food or inappropriate choice of placebo food/diets. Provision of study diets as the preferred delivery method can somewhat address these limitations, although allowing good adherence compared with education-based dietary interventions. Issues associated with participant expectancies and dietary behaviors can alter the true effectiveness of a diet. In addition, failure to adjust for or report baseline intake of nutrients of interest can reduce their magnitude of benefit. Bias in subjective reports and choice of measurement tools can preclude accurate assessment of food-intake data. In the design of elimination and rechallenge studies, sufficient time period and adequate exclusion of dietary triggers are essential to ensure symptoms are well-controlled before rechallenging. The route and frequency of challenging, design of test food, and/or placebo should match the aims of the rechallenge phase. Long-term efficacy data of such therapeutic diets has been poorly documented in most studies. Standardized guidelines that address many of the challenges outlined above are suggested to strengthen the quality of evidence for dietary therapies in FGID.

Food choice as a key management strategy for functional gastrointestinal symptoms.

Recognition of food components that induce functional gut symptoms in patient's functional bowel disorders (FBD) has been challenging. Food directly or indirectly provides considerable afferent input into the enteric nervous system. There is an altered relationship between the afferent input and perception/efferent response in FBD. Defining the nature of food-related stimuli may provide a means of minimizing such an input and gut symptoms. Using this premise, reducing the intake of FODMAPs (fermentable oligo-, di-, and mono-saccharides and polyols)--poorly absorbed short-chain carbohydrates that, by virtue of their small molecular size and rapid fermentability, will distend the intestinal lumen with liquid and gas--improves symptoms in the majority of patients. Well-developed methodologies to deliver the diet via dietician-led education are available. Another abundant source of afferent input is natural and added food chemicals (such as salicylates, amines, and glutamates). Studies are needed to assess the efficacy of the low food chemical dietary approach. A recent placebo-controlled trial of FODMAP-poor gluten provided the first valid evidence that non-celiac gluten intolerance might actually exist, but its prevalence and underlying mechanisms require elucidation. Food choice via the low FODMAP and potentially other dietary strategies is now a realistic and efficacious therapeutic approach for functional gut symptoms.

Gluten causes gastrointestinal symptoms in subjects without celiac disease: a double-blind randomized placebo-controlled trial.

OBJECTIVES: Despite increased prescription of a gluten-free diet for gastrointestinal symptoms in individuals who do not have celiac disease, there is minimal evidence that suggests that gluten is a trigger. The aims of this study were to determine whether gluten ingestion can induce symptoms in non-celiac individuals and to examine the mechanism. METHODS: A double-blind, randomized, placebo-controlled rechallenge trial was undertaken in patients with irritable bowel syndrome in whom celiac disease was excluded and who were symptomatically controlled on a gluten-free diet. Participants received either gluten or placebo in the form of two bread slices plus one muffin per day with a gluten-free diet for up to 6 weeks. Symptoms were evaluated using a visual analog scale and markers of intestinal inflammation, injury, and immune activation were monitored. RESULTS: A total of 34 patients (aged 29-59 years, 4 men) completed the study as per protocol. Overall, 56% had human leukocyte antigen (HLA)-DQ2 and/or HLA-DQ8. Adherence to diet and supplements was very high. Of 19 patients (68%) in the gluten group, 13 reported that symptoms were not adequately controlled compared with 6 of 15 (40%) on placebo (P=0.0001; generalized estimating equation). On a visual analog scale, patients were significantly worse with gluten within 1 week for overall symptoms (P=0.047), pain (P=0.016), bloating (P=0.031), satisfaction with stool consistency (P=0.024), and tiredness (P=0.001). Anti-gliadin antibodies were not induced. There were no significant changes in fecal lactoferrin, levels of celiac antibodies, highly sensitive C-reactive protein, or intestinal permeability. There were no differences in any end point in individuals with or without DQ2/DQ8. CONCLUSIONS: "Non-celiac gluten intolerance" may exist, but no clues to the mechanism were elucidated.

Evidence-based dietary management of functional gastrointestinal symptoms: The FODMAP approach.

BACKGROUND AND AIM: Functional gastrointestinal symptoms are common and their management is often a difficult clinical problem. The link between food intake and symptom induction is recognized. This review aims to describe the evidence base for restricting rapidly fermentable, short-chain carbohydrates (FODMAPs) in controlling such symptoms. METHODS: The nature of FODMAPs, their mode of action in symptom induction, results of clinical trials and the implementation of the diet are described. RESULTS: FODMAPs are widespread in the diet and comprise a monosaccharide (fructose), a disaccharide (lactose), oligosaccharides (fructans and galactans), and polyols. Their ingestion increases delivery of readily fermentable substrate and water to the distal small intestine and proximal colon, which are likely to induce luminal distension and induction of functional gut symptoms. The restriction of their intake globally (as opposed to individually) reduces functional gut symptoms, an effect that is durable and can be reversed by their reintroduction into the diet (as shown by a randomized placebo-controlled trial). The diet has a high compliance rate. However it requires expert delivery by a dietitian trained in the diet. Breath hydrogen tests are useful to identify individuals who can completely absorb a load of fructose and lactose so that dietary restriction can be less stringent. CONCLUSIONS: The low FODMAP diet provides an effective approach to the management of patients with functional gut symptoms. The evidence base is now sufficiently strong to recommend its widespread application.

Measurement of short-chain carbohydrates in common Australian vegetables and fruits by high-performance liquid chromatography (HPLC).

Fermentable oligo-, di-, and monosaccharides and polyols (FODMAPs) are short-chain carbohydrates that can be poorly absorbed by the small intestine and may have a wide range of effects on gastrointestinal processes. FODMAPs include lactose, fructose in excess of glucose, fructans and fructooligosaccharides (FOS, nystose, kestose), galactooligosaccharides (GOS, raffinose, stachyose), and sugar polyols (sorbitol, mannitol). This paper describes an analytical approach based on HPLC with ELSD that quantifies the major FODMAPs in 45 vegetables and 41 fruits. Sorbitol and/or mannitol were measured in 18 vegetables (range = 0.09-2.96 g/100 g of fw), raffinose and/or stachyose in 7 vegetables (0.08-0.68 g/100 g of fw), and nystose and/or kestose in 19 vegetables (0.02-0.71 g/100 g of fw). Apple, pear, mango, clingstone peach, and watermelon all contained fructose in excess of glucose. Sorbitol was measured in 15 fruits (0.53-5.99 g/100 g of fw), mannitol was found in 2 fruits, and nystose or kestose was measured in 8 fruits. Understanding the importance of dietary FODMAPs will be greatly assisted by comprehensive food composition data.

Strategies to manage gastrointestinal symptoms complicating enteral feeding.

Diarrhea and abdominal distension are common complications associated with enteral feeding. Often the cause is unknown, the enteral formula is blamed and changes to the mode of delivery or formula are instituted. However, the evidence base for many strategies used is limited. Altering the osmolality and temperature of the formula and/or the rate of infusion are commonly practiced but evidence for their benefit is largely anecdotal. Preventing microbial contamination of the feed is important and clear guidelines exist to achieve this. The formulation itself can be modified. While the addition of fiber is well supported theoretically, outcome data are less convincing. Avoidance of osmotically active, poorly absorbed short-chain carbohydrates in the formula (often used as the major carbohydrate source) is a new tactic to minimize diarrhea. It has compelling theoretical support, but requires further investigation. A methodical clinical approach to gastrointestinal complications of enteral feeding is warranted and an algorithm for management is proposed.

Dietary triggers of abdominal symptoms in patients with irritable bowel syndrome: randomized placebo-controlled evidence.

BACKGROUND & AIMS: Observational studies suggest dietary fructose restriction might lead to sustained symptomatic response in patients with irritable bowel syndrome (IBS) and fructose malabsorption. The aims of this study were first to determine whether the efficacy of this dietary change is due to dietary fructose restriction and second to define whether symptom relief was specific to free fructose or to poorly absorbed short-chain carbohydrates in general. METHODS: The double-blinded, randomized, quadruple arm, placebo-controlled rechallenge trial took place in the general community. The 25 patients who had responded to dietary change were provided all food, low in free fructose and fructans, for the duration of the study. Patients were randomly challenged by graded dose introduction of fructose, fructans, alone or in combination, or glucose taken as drinks with meals for maximum test period of 2 weeks, with at least 10-day washout period between. For the main outcome measures, symptoms were monitored by daily diary entries and responses to a global symptom question. RESULTS: Seventy percent of patients receiving fructose, 77% receiving fructans, and 79% receiving a mixture reported symptoms were not adequately controlled, compared with 14% receiving glucose (P < or = 0.002, McNemar test). Similarly, the severity of overall and individual symptoms was significantly and markedly less for glucose than other substances. Symptoms were induced in a dose-dependent manner and mimicked previous IBS symptoms. CONCLUSIONS: In patients with IBS and fructose malabsorption, dietary restriction of fructose and/or fructans is likely to be responsible for symptomatic improvement, suggesting efficacy is due to restriction of poorly absorbed short-chain carbohydrates in general.

Pilot study on the effect of reducing dietary FODMAP intake on bowel function in patients without a colon.

BACKGROUND: Poorly absorbed short-chain carbohydrates (FODMAPs) in the diet should, by virtue of their osmotic effects, increase fecal output following colectomy and ileal pouch formation or ileorectal anastomosis (IRA). The aim was to perform a proof-of-concept evaluation of this hypothesis. METHODS: Fifteen patients (13 pouch, 2 IRA) had dietary and symptomatic evaluation before and during a low FODMAP diet. Carbohydrate malabsorption was evaluated by breath tests. Pouchitis was assessed clinically/endoscopically or by fecal lactoferrin. RESULTS: Of 8 patients with a breath hydrogen response to lactulose, 7 had fructose malabsorption, 3 with lactose malabsorption, and 1 had lactose malabsorption alone. Five of 7 studied retrospectively improved stool frequency (from median 8 to 4 per day; P = 0.02), this being sustained over 0.5-3 years of follow-up. Five of 8 patients completed a prospective arm of the study. One patient had sustained improvement in stool frequency and 1 had reduced wind production. Overall, none of 8 patients who had pouchitis improved. In contrast, median daily stool frequency fell from 8 to 4 (P = 0.001) in the 7 without pouchitis. The degree of change in FODMAP intake also predicted response. There was a tendency for pouchitis to be associated with low baseline FODMAP intake. CONCLUSIONS: There is a high prevalence of carbohydrate malabsorption in these patients. Reduction of the intake of FODMAPs may be efficacious in reducing stool frequency in patients without pouchitis, depending on dietary adherence and baseline diet.

Fructan and free fructose content of common Australian vegetables and fruit.

Fructans are not digested in the small intestines of humans. While many health benefits have been attributed to these carbohydrates, they can cause gastrointestinal symptoms in some individuals. We measured the total fructans in 60 vegetables and 43 fruits using the Megazyme fructan assay. Vegetables with the highest quantity of fructans included garlic, artichoke, shallots, leek bulb, and onions (range, 1.2-17.4 g/100 g fw). Fruits with low, but detectable, fructans included longon, white peach, persimmon, and melon (range, 0.21-0.46 g/100 g fw). The fructan assay was modified to provide an estimate of the average chain length (degree of polymerization) for high fructan vegetables. d-Fructose can also be malabsorbed in the small intestine of humans, so the d-fructose content in some foods was measured to supplement the current food tables. Research in this area will be facilitated through the availability of more comprehensive food composition data.

Fructose malabsorption and symptoms of irritable bowel syndrome: guidelines for effective dietary management.

Dietary fructose induces abdominal symptoms in patients with fructose malabsorption, but there are no published guidelines on its dietary management. The objective was to retrospectively evaluate a potentially successful diet therapy in patients with irritable bowel syndrome and fructose malabsorption. Tables detailing the content of fructose and fructans in foods were constructed. A dietary strategy comprising avoidance of foods containing substantial free fructose and short-chain fructans, limitation of the total dietary fructose load, encouragement of foods in which glucose was balanced with fructose, and co-ingestion of free glucose to balance excess free fructose was devised. Sixty-two consecutively referred patients with irritable bowel syndrome and fructose malabsorption on breath hydrogen testing underwent dietary instruction. Dietary adherence and effect on abdominal symptoms were evaluated via telephone interview 2 to 40 months (median 14 months) later. Response to the diet was defined as improvement of all symptoms by at least 5 points on a -10- to 10-point scale. Forty-eight patients (77%) adhered to the diet always or frequently. Forty-six (74%) of all patients responded positively in all abdominal symptoms. Positive response overall was significantly better in those adherent than nonadherent (85% vs 36%; P<0.01), as was improvement in individual symptoms (P<0.01 for all symptoms). This comprehensive fructose malabsorption dietary therapy achieves a high level of sustained adherence and good symptomatic response.