Irritable bowel syndrome (IBS), with its key features of abdominal pain and disturbed bowel habit, is thought by both patients and clinicians to be strongly influenced by diet. However, the ...complexities of diet have made identifying specific food intolerances difficult. Eating disorders can masquerade as IBS and may need specialist treatment. While typical food allergy is readily distinguished from IBS, the mechanisms of gut-specific adverse reactions to food are only just being defined. These may include gut-specific mast cell activation as well as non-specific activation by stressors and certain foods. Visceral hypersensitivity, in some cases mediated by mast cell activation, plays a key part in making otherwise innocuous gut stimuli painful. Rapidly fermented poorly absorbed carbohydrates produce gaseous distension as well as short-chain fatty acids and lowering of colonic pH which may cause symptoms in IBS patients. Limiting intake of these in low FODMAP and related diets has proven popular and apparently successful in many patients. Existing diet, colonic microbiota and their metabolic products may be helpful in predicting who will respond. Wheat intolerance may reflect the fact that wheat is often a major source of dietary FODMAPs. It may also be either a forme fruste of coeliac disease or non-specific immune activation. Wheat exclusion can be successful in some of these patients. More research is needed to fully understand the mechanisms of food intolerances and how to best ameliorate them in a personalised medicine approach to diet in IBS.
How do FODMAPs work? Spiller, Robin
Journal of gastroenterology and hepatology,
March 2017, Letnik:
32, Številka:
S1
Journal Article
Recenzirano
Odprti dostop
Many patients report symptoms come on after eating, and experience with exclusion diets suggests that certainly poorly absorbed but rapidly fermentable carbohydrates may be responsible. While ...monomeric and short chain carbohydrate polymers exert osmotic forces and trap water in the small bowel with acceleration of transit, the longer polymer polymers such as inulin pass through the small bowel unaltered but are fermented in the colon where they may cause distension and symptoms. Recent developments in magnetic resonance imaging confirm the importance of fructose in stimulating small bowel water secretion and its negation by the presence of glucose. Fructans have no impact on the small intestine but cause colonic distension and symptoms including bloating.
The acute phase of IBD with inflamed gut and often ulcerated mucosa is clearly different from the apparently normal mucosa characteristic of IBS. However, more detailed assessment has detected immune ...activation, increased gut permeability, increased mucosal serotonin availability, abnormalities of enteric nerve structure and function, and dysbiosis in gut microbiota in IBS - all features seen in IBD. Furthermore, as treatments for inflammation in IBD have become more effective it is now apparent that ∼1 in 3 patients with IBD in remission from inflammation still have persistent abnormalities of sensation, motility and gut microbiota, which might cause IBS-like symptoms. This Perspective explores the overlap between IBS and IBD and their treatments, proposing future directions for research in this stimulating area.
It is increasingly perceived that gut host-microbial interactions are important elements in the pathogenesis of functional gastrointestinal disorders (FGID). The most convincing evidence to date is ...the finding that functional dyspepsia and irritable bowel syndrome (IBS) may develop in predisposed individuals following a bout of infectious gastroenteritis. There has been a great deal of interest in the potential clinical and therapeutic implications of small intestinal bacterial overgrowth in IBS. However, this theory has generated much debate because the evidence is largely based on breath tests which have not been validated. The introduction of culture-independent molecular techniques provides a major advancement in our understanding of the microbial community in FGID. Results from 16S rRNA-based microbiota profiling approaches demonstrate both quantitative and qualitative changes of mucosal and faecal gut microbiota, particularly in IBS. Investigators are also starting to measure host-microbial interactions in IBS. The current working hypothesis is that abnormal microbiota activate mucosal innate immune responses which increase epithelial permeability, activate nociceptive sensory pathways and dysregulate the enteric nervous system. While we await important insights in this field, the microbiota is already a therapeutic target. Existing controlled trials of dietary manipulation, prebiotics, probiotics, synbiotics and non-absorbable antibiotics are promising, although most are limited by suboptimal design and small sample size. In this article, the authors provide a critical review of current hypotheses regarding the pathogenetic involvement of microbiota in FGID and evaluate the results of microbiota-directed interventions. The authors also provide clinical guidance on modulation of gut microbiota in IBS.
Despite being one of the most common conditions leading to gastroenterological referral, irritable bowel syndrome (IBS) is poorly understood. However, recent years have seen major advances. These ...include new understanding of the role of both inflammation and altered microbiota as well as the impact of dietary intolerances as illuminated by magnetic resonance imaging (MRI), which has thrown new light on IBS. This article will review new data on how excessive bile acid secretion mediates diarrhea and evidence from post infectious IBS which has shown how gut inflammation can alter gut microbiota and function. Studies of patients with inflammatory bowel disease (IBD) have also shown that even when inflammation is in remission, the altered enteric nerves and abnormal microbiota can generate IBS-like symptoms. The efficacy of the low FODMAP diet as a treatment for bloating, flatulence, and abdominal discomfort has been demonstrated by randomized controlled trials. MRI studies, which can quantify intestinal volumes, have provided new insights into how FODMAPs cause symptoms. This article will focus on these areas together with recent trials of new agents, which this author believes will alter clinical practice within the foreseeable future.
Ingestion of poorly digested, fermentable carbohydrates (fermentable oligo-, di-, mono-saccharides and polyols; FODMAPs) have been implicated in exacerbating intestinal symptoms and the reduction of ...intake with symptom alleviation. Restricting FODMAP intake is believed to relieve colonic distension by reducing colonic fermentation but this has not been previously directly assessed. We performed a randomised controlled trial comparing the effect of a low FODMAP diet combined with either maltodextrin or oligofructose on colonic contents, metabolites and microbiota.
A parallel randomised controlled trial in healthy adults (n = 37). All subjects followed a low FODMAP diet for a week and supplemented their diet with either maltodextrin (MD) or oligofructose (OF) 7g twice daily. Fasted assessments performed pre- and post-diet included MRI to assess colonic volume, breath testing for hydrogen and methane, and stool collection for microbiota analysis.
The low FODMAP diet was associated with a reduction in Bifidobacterium and breath hydrogen, which was reversed by oligofructose supplementation. The difference in breath hydrogen between groups post-intervention was 27ppm (95% CI 7 to 50, P<0.01). Colonic volume increased significantly from baseline in both groups (OF increased 110ml (19.6%), 95% CI 30ml to 190ml, P = 0.01; MD increased 90ml (15.5%), 95% CI 6ml to 175ml, P = 0.04) with no significant difference between them. Colonic volumes correlated with total breath hydrogen + methane. A divergence in Clostridiales abundance was observed with increased abundance of Ruminococcaceae in the maltodextrin group, while in the oligofructose group, Lachnospiraceae decreased. Subjects in either group with high methane production also tended to have high microbial diversity, high colonic volume and greater abundance of methanogens.
A low FODMAP diet reduces total bacterial count and gas production with little effect on colonic volume.
The objective of this study was to investigate whether ingestion of fructose and fructans (such as inulin) can exacerbate irritable bowel syndrome (IBS) symptoms. The aim was to better understand the ...origin of these symptoms by magnetic resonance imaging (MRI) of the gut.
A total of 16 healthy volunteers participated in a four-way, randomized, single-blind, crossover study in which they consumed 500 ml of water containing 40 g of either glucose, fructose, inulin, or a 1:1 mixture of 40 g glucose and 40 g fructose. MRI scans were performed hourly for 5 h, assessing the volume of gastric contents, small bowel water content (SBWC), and colonic gas. Breath hydrogen (H2) was measured and symptoms recorded after each scan.
Data are reported as mean (s.d.) (95% CI) when normally distributed and median (range) when not. Fructose increased area under the curve (AUC) from 0-5 h of SBWC to 71 (23) l/min, significantly greater than for glucose at 36 (11-132) l/min (P<0.001), whereas AUC SBWC after inulin, 33 (17-106) l/min, was no different from that after glucose. Adding glucose to fructose decreased AUC SBWC to 55 (28) l/min (P=0.08) vs. fructose. Inulin substantially increased AUC colonic gas to 33 (20) l/min, significantly greater than glucose and glucose+fructose (both P<0.05). Breath H2 rose more with inulin than with fructose. Glucose when combined with fructose significantly reduced breath H2 by 7,700 (3,121-12,300) p.p.m./min relative to fructose alone (P<0.01, n=13).
Fructose but not inulin distends the small bowel with water. Adding glucose to fructose reduces the effect of fructose on SBWC and breath hydrogen. Inulin distends the colon with gas more than fructose, but causes few symptoms in healthy volunteers.
The rate and extent of drug dissolution and absorption from solid oral dosage forms is highly dependent upon the volumes and distribution of gastric and small intestinal water. However, little is ...known about the time courses and distribution of water volumes in vivo in an undisturbed gut. Previous imaging studies offered a snapshot of water distribution in fasted humans and showed that water in the small intestine is distributed in small pockets. This study aimed to quantify the volume and number of water pockets in the upper gut of fasted healthy humans following ingestion of a glass of water (240 mL, as recommended for bioavailability/bioequivalence (BA/BE) studies), using recently validated noninvasive magnetic resonance imaging (MRI) methods. Twelve healthy volunteers underwent upper and lower abdominal MRI scans before drinking 240 mL (8 fluid ounces) of water. After ingesting the water, they were scanned at intervals for 2 h. The drink volume, inclusion criteria, and fasting conditions matched the international standards for BA/BE testing in healthy volunteers. The images were processed for gastric and intestinal total water volumes and for the number and volume of separate intestinal water pockets larger than 0.5 mL. The fasted stomach contained 35 ± 7 mL (mean ± SEM) of resting water. Upon drinking, the gastric fluid rose to 242 ± 9 mL. The gastric water volume declined rapidly after that with a half emptying time (T 50%) of 13 ± 1 min. The mean gastric volume returned back to baseline 45 min after the drink. The fasted small bowel contained a total volume of 43 ± 14 mL of resting water. Twelve minutes after ingestion of water, small bowel water content rose to a maximum value of 94 ± 24 mL contained within 15 ± 2 pockets of 6 ± 2 mL each. At 45 min, when the glass of water had emptied completely from the stomach, total intestinal water volume was 77 ± 15 mL distributed into 16 ± 3 pockets of 5 ± 1 mL each. MRI provided unprecedented insights into the time course, number, volume, and location of water pockets in the stomach and small intestine under conditions that represent standard BA/BE studies using validated techniques. These data add to our current understanding of gastrointestinal physiology and will help improve physiological relevance of in vitro testing methods and in silico transport analyses for prediction of bioperformance of oral solid dosage forms, particularly for low solubility Biopharmaceutics Classification System (BCS) Class 2 and Class 4 compounds.
Irritable bowel syndrome (IBS) is a heterogeneous functional disorder with a multifactorial etiology that involves the interplay of both host and environmental factors. Among environmental factors ...relevant for IBS etiology, the diet stands out given that the majority of IBS patients report their symptoms to be triggered by meals or specific foods. The diet provides substrates for microbial fermentation, and, as the composition of the intestinal microbiota is disturbed in IBS patients, the link between diet, microbiota composition, and microbial fermentation products might have an essential role in IBS etiology. In this review, we summarize current evidence regarding the impact of diet and the intestinal microbiota on IBS symptoms, as well as the reported interactions between diet and the microbiota composition. On the basis of the existing data, we suggest pathways (mechanisms) by which diet components, via the microbial fermentation, could trigger IBS symptoms. Finally, this review provides recommendations for future studies that would enable elucidation of the role of diet and microbiota and how these factors may be (inter)related in the pathophysiology of IBS.
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