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Gut Microbial Metabolites and Biochemical Pathways Involved in Irritable Bowel Syndrome: Effects of Diet and Nutrition on the Microbiome.
James, SC, Fraser, K, Young, W, McNabb, WC, Roy, NC
The Journal of nutrition. 2020;(5):1012-1021
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Abstract
The food we consume and its interactions with the host and their gut microbiota affect normal gut function and health. Functional gut disorders (FGDs), including irritable bowel syndrome (IBS), can result from negative effects of these interactions, leading to a reduced quality of life. Certain foods exacerbate or reduce the severity and prevalence of FGD symptoms. IBS can be used as a model of perturbation from normal gut function with which to study the impact of foods and diets on the severity and symptoms of FGDs and understand how critical processes and biochemical mechanisms contribute to this impact. Analyzing the complex interactions between food, host, and microbial metabolites gives insights into the pathways and processes occurring in the gut which contribute to FGDs. The following review is a critical discussion of the literature regarding metabolic pathways and dietary interventions relevant to FGDs. Many metabolites, for example bile acids, SCFAs, vitamins, amino acids, and neurotransmitters, can be altered by dietary intake, and could be valuable for identifying perturbations in metabolic pathways that distinguish a "normal, healthy" gut from a "dysfunctional, unhealthy" gut. Dietary interventions for reducing symptoms of FGDs are becoming more prevalent, but studies investigating the underlying mechanisms linked to host, microbiome, and metabolite interactions are less common. Therefore, we aim to evaluate the recent literature to assist with further progression of research in this field.
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Irritable bowel syndrome and diet: where are we in 2018?
Dimidi, E, Rossi, M, Whelan, K
Current opinion in clinical nutrition and metabolic care. 2017;(6):456-463
Abstract
PURPOSE OF REVIEW The aim is to review the most recent advances in the evidence supporting the use of various dietary interventions for the management of irritable bowel syndrome (IBS). RECENT FINDINGS There is insufficient evidence of the effect of fibres other than psyllium in IBS, whereas the recent studies on prebiotics suggest a limited effect in IBS. Recent probiotic trials continue to provide varying results, with some probiotic strains exhibiting beneficial effects, whereas others show no effect. Recent trials have also confirmed the clinical effectiveness of a diet low in fermentable oligosaccharides, disaccharides, monosaccharides and polyols (i.e. low FODMAP diet) in IBS. Although gluten sensitivity has also been recently investigated, its presence cannot be confirmed yet because of the presence of other potential contributing compounds in wheat. Studies also suggest a potential beneficial effect of peppermint oil, which warrants further research. SUMMARY It is clear that a low FODMAP diet has a beneficial effect in a majority of patients with IBS. Probiotics also have great potential in the management of IBS; however, it is still unclear which strains and doses are the most beneficial. Further research is needed on the effect of different fibres, or combinations of fibres, in IBS.
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The role of bile acids in the pathogenesis of bowel diseases.
Panek-Jeziorna, M, Mulak, A
Postepy higieny i medycyny doswiadczalnej (Online). 2017;(1):737-746
Abstract
Bile acids not only play a cardinal role in the digestion and absorption of fat and fat-soluble vitamins, but also significantly affect gastrointestinal motor, sensory and secretory functions, intestinal barrier permeability and the regulation of the inflammatory response. The results of recent studies have revealed complex interactions between bile acids and the gut microbiota. In addition, bile acids also play a role of signaling molecules regulating the activity of lipid and glucose metabolic pathways, as well as a role of ligands for transcription factors. Genetic factors associated with the regulation of bile acid synthesis, transport and action may significantly influence gastrointestinal function and predispose to diarrhea resulting from bile acid malabsorption. Methods used in the diagnosis of bile acid malabsorption include 75selenium-homotaurocholic acid test, serum C4 and fibroblast growth factor 19 (FGF19), as well as fecal bile acid levels. The paper presents the latest data on the role of bile acid in the pathogenesis of irritable bowel syndrome, inflammatory bowel diseases and colorectal cancer. Advances in the treatment of disturbances in bile acids absorption and synthesis are also presented. A better understanding of molecular mechanisms regulating bile acid action may have implication for colorectal cancer prevention.
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Serotonergic reinforcement of intestinal barrier function is impaired in irritable bowel syndrome.
Keszthelyi, D, Troost, FJ, Jonkers, DM, van Eijk, HM, Lindsey, PJ, Dekker, J, Buurman, WA, Masclee, AA
Alimentary pharmacology & therapeutics. 2014;(4):392-402
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Abstract
BACKGROUND Alterations in serotonergic (5-HT) metabolism and/or intestinal integrity have been associated with irritable bowel syndrome (IBS). AIMS To assess the effects of the precursor of 5-HT, 5-hydroxytryptophan (5-HTP), on mucosal 5-HT availability and intestinal integrity, and to assess potential differences between healthy controls and IBS patients. METHODS Fifteen IBS patients and 15 healthy volunteers participated in this randomised double-blind placebo-controlled study. Intestinal integrity was assessed by dual-sugar test and by determining the mucosal expression of tight junction proteins after ingestion of an oral bolus of 100 mg 5-HTP or placebo. Mucosal serotonergic metabolism was assessed in duodenal biopsy samples. RESULTS 5-HTP administration significantly increased mucosal levels of 5-HIAA, the main metabolite of 5-HT, in both healthy controls (7.1 ± 1.7 vs. 2.5 ± 0.7 pmol/mg, 5-HTP vs. placebo, P = 0.02) and IBS patients (20.0 ± 4.8 vs. 8.1 ± 1.3 pmol/mg, 5-HTP vs. placebo, P = 0.02), with the latter group showing a significantly larger increase. Lactulose/L-rhamnose ratios were significantly lower after administration of 5-HTP (P < 0.05) in healthy controls and were accompanied by redistribution of zonula occludens-1 (ZO-1), pointing to reinforcement of the barrier. In IBS, expression of the tight junction proteins was significantly lower compared to healthy controls, and 5-HTP resulted in a further decrease in occludin expression. CONCLUSIONS Oral 5-HTP induced alterations in mucosal 5-HT metabolism. In healthy controls, a reinforcement of the intestinal barrier was seen whereas such reaction was absent in IBS patients. This could indicate the presence of a serotonin-mediated mechanism aimed to reinforce intestinal barrier function, which seems to dysfunction in IBS patients.
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The role of FODMAPs in irritable bowel syndrome.
Shepherd, SJ, Halmos, E, Glance, S
Current opinion in clinical nutrition and metabolic care. 2014;(6):605-9
Abstract
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.
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An update on the use and investigation of probiotics in health and disease.
Sanders, ME, Guarner, F, Guerrant, R, Holt, PR, Quigley, EM, Sartor, RB, Sherman, PM, Mayer, EA
Gut. 2013;(5):787-96
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Abstract
Probiotics are derived from traditional fermented foods, from beneficial commensals or from the environment. They act through diverse mechanisms affecting the composition or function of the commensal microbiota and by altering host epithelial and immunological responses. Certain probiotic interventions have shown promise in selected clinical conditions where aberrant microbiota have been reported, such as atopic dermatitis, necrotising enterocolitis, pouchitis and possibly irritable bowel syndrome. However, no studies have been conducted that can causally link clinical improvements to probiotic-induced microbiota changes. Whether a disease-prone microbiota pattern can be remodelled to a more robust, resilient and disease-free state by probiotic administration remains a key unanswered question. Progress in this area will be facilitated by: optimising strain, dose and product formulations, including protective commensal species; matching these formulations with selectively responsive subpopulations; and identifying ways to manipulate diet to modify bacterial profiles and metabolism.
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Metabolic and toxicological considerations for the latest drugs used to treat irritable bowel syndrome.
Mozaffari, S, Nikfar, S, Abdollahi, M
Expert opinion on drug metabolism & toxicology. 2013;(4):403-21
Abstract
INTRODUCTION The high prevalence of irritable bowel syndrome (IBS), a chronic gastrointestinal (GI) disorder, its lack of satisfactory effective drugs and its complicated pathophysiology lead to the demand of new therapeutic agents. During a new drug development process, the pharmacokinetic profiling is of a great considerable importance comparable to drug's efficacy. This involves the drug's absorption, distribution, metabolism and excretion, all of which are crucial to its usefulness. In addition, the toxicological profile and possible adverse reactions of the drug should be identified. Also its interactions should be identified at different phases of trials. Several pharmacokinetic studies are carried out to achieve drugs with the best absorption and bioavailability and the least adverse effects and lowest toxicity. AREAS COVERED To make an update on new clinically introduced drugs for IBS and their dynamics and kinetics data, the present systematic review was accomplished. All relevant bibliographic databases were searched from the year 2003 up to May 2012 to identify all clinical trials that evaluated the potential efficacy of a novel agent in IBS. EXPERT OPINION Some evaluated drugs, such as ramosetron (5-HT3 antagonist) and pexacerfont (CRF1 receptor antagonist), have shown some benefits in diarrhea-predominant IBS (D-IBS), while, prucalopride and mosapride (5-HT4 agonist) with prokinetic effect were found useful in constipation-predominant IBS (C-IBS). Besides, dexloxiglumide, lubiprostone and linaclotide have shown beneficial effects in C-IBS patients. Melatonin regulates GI tract motility and, asimadoline, gabapentin and pregabalin show reduction of pain threshold and visceral hypersensitivity. Glucagon-like peptide analog, calcium-channel blockers and neurokinin receptor antagonists have shown benefits in pain attacks. More time is required to indicate both efficacy and safety in long-term treatment due to multifactorial pathophysiology, variations in individual responses and insufficient assessment methods, which limit the right decision-making process about the efficacy and tolerability of these new drugs.
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The colonic microbiota and colonic disease.
Shanahan, F
Current gastroenterology reports. 2012;(5):446-52
Abstract
The colonic ecosystem differs from that in the proximal gut in several important respects. The colonic microbiota represents the largest population of microbes colonizing humans from birth. Constraints on bacterial numbers, composition, and interaction with the host involve not only the innate and acquired immune system, but also the colonic mucin structure. While the microbiota provides beneficial protective, trophic, nutritional, and metabolic signals for the host, it may become a risk factor for disease depending on context and host susceptibility. Technological advances including DNA-based high-throughput compositional analysis have linked changes in the indigenous microbiota with several human diseases. In some instances, these findings have the potential to serve as new biomarkers of risk of disease. In this overview, recent advances are focused upon in relation to irritable bowel syndrome, inflammatory bowel disease, and colon cancer. The possibility that the therapeutic solution to some of these disorders may reside within the microbiota will also be addressed.
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Bacterial metabolic 'toxins': a new mechanism for lactose and food intolerance, and irritable bowel syndrome.
Campbell, AK, Matthews, SB, Vassel, N, Cox, CD, Naseem, R, Chaichi, J, Holland, IB, Green, J, Wann, KT
Toxicology. 2010;(3):268-76
Abstract
Lactose and food intolerance cause a wide range of gut and systemic symptoms, including gas, gut pain, diarrhoea or constipation, severe headaches, severe fatigue, loss of cognitive functions such as concentration, memory and reasoning, muscle and joint pain, heart palpitations, and a variety of allergies (Matthews and Campbell, 2000; Matthews et al., 2005; Waud et al., 2008). These can be explained by the production of toxic metabolites from gut bacteria, as a result of anaerobic digestion of carbohydrates and other foods, not absorbed in the small intestine. These metabolites include alcohols, diols such as butan 2,3 diol, ketones, acids, and aldehydes such as methylglyoxal (Campbell et al., 2005, 2009). These 'toxins' induce calcium signals in bacteria and affect their growth, thereby acting to modify the balance of microflora in the gut (Campbell et al., 2004, 2007a,b). These bacterial 'toxins' also affect signalling mechanisms in cells around the body, thereby explaining the wide range of symptoms in people with food intolerance. This new mechanism also explains the most common referral to gastroenterologists, irritable bowel syndrome (IBS), and the illness that afflicted Charles Darwin for 50 years (Campbell and Matthews, 2005a,b). We propose it will lead to a new understanding of the molecular mechanism of type 2 diabetes and some cancers.
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Irritable bowel syndrome: can nutrient manipulation help?
Cabré, E
Current opinion in clinical nutrition and metabolic care. 2010;(5):581-7
Abstract
PURPOSE OF REVIEW To describe the evidences for the usefulness of dietary manipulations (including the use of probiotics and prebiotics) in the management of irritable bowel syndrome (IBS). RECENT FINDINGS Exclusion diets do not have a role in the management of these patients except in the case of malabsorbed sugars (lactose, fructose). However, recent work suggests that excluding these sugars is more effective in non-IBS than in IBS patients. Also, the first small open series on the use of very low (20 g/day) carbohydrate diet (VLCD) in IBS has been published with promising results. However, safety concerns do not allow us to recommend them. In the period of review, further evidence has been provided on the role of psyllium in IBS. Also, the available evidence on the use of probiotics in IBS has been meta-analyzed. SUMMARY IBS patients should eat a balanced diet without restrictions, and (except for malabsorbed sugars) exclusion diets are not useful in most of them. The role of VLCD remains to be established. The concept that increasing fiber intake is useful for IBS may not be true for all patients, and hydrophilic colloids (e.g. psyllium) are preferred. There is growing evidence for the effectiveness of probiotics in IBS.