Some useful links

There is plenty of basic information on dietary therapy throughout the Internet. If you are interested in the latest medical findings you should consult the global database PUBMED of the medical publications. Below are examples of IBS-related studies:

Diet in Irritable Bowel Syndrome (IBS): Interaction with Gut Microbiota and Gut Hormones.

Diet plays an important role not only in the pathophysiology of irritable bowel syndrome (IBS), but also as a tool that improves symptoms and quality of life. The effects of diet seem to be a result of an interaction with the gut bacteria and the gut endocrine cells. The density of gut endocrine cells is low in IBS patients, and it is believed that this abnormality is the direct cause of the symptoms seen in IBS patients. The low density of gut endocrine cells is probably caused by a low number of stem cells and low differentiation progeny toward endocrine cells. A low fermentable oligo-, di-, monosaccharide, and polyol (FODMAP) diet and fecal microbiota transplantation (FMT) restore the gut endocrine cells to the level of healthy subjects. It has been suggested that our diet acts as a prebiotic that favors the growth of a certain types of bacteria. Diet also acts as a substrate for gut bacteria fermentation, which results in several by-products. These by-products might act on the stem cells in such a way that the gut stem cells decrease, and consequently, endocrine cell numbers decrease. Changing to a low-FODMAP diet or changing the gut bacteria through FMT improves IBS symptoms and restores the density of endocrine cells.

KEYWORDS: IBS, diet, fecal microbiota transplantation, gut endocrine cells, gut microbiota

Cytidine Diphosphate-Ribitol Analysis for Diagnostics and Treatment Monitoring of Cytidine Diphosphate-L-Ribitol Pyrophosphorylase A Muscular Dystrophy.

Many muscular dystrophies currently remain untreatable. Recently, dietary ribitol has been suggested as a treatment for cytidine diphosphate (CDP)-L-ribitol pyrophosphorylase A (CRPPA, ISPD), fukutin (FKTN), and fukutin-related protein (FKRP) myopathy, by raising CDP-ribitol concentrations. Thus, to facilitate fast diagnosis, treatment development, and treatment monitoring, sensitive detection of CDP-ribitol is required. An LC-MS method was optimized for CDP-ribitol in human and mice cells and tissues. CDP-ribitol, the product of CRPPA, was detected in all major human and mouse tissues. Moreover, CDP-ribitol concentrations were reduced in fibroblasts and skeletal muscle biopsies from patients with CRPPA, showing that CDP-ribitol could serve as a diagnostic marker to identify patients with CRPPA with severe Walker-Warburg syndrome and mild limb-girdle muscular dystrophy (LGMD) phenotypes. A screen for potentially therapeutic monosaccharides revealed that ribose, in addition to ribitol, restored CDP-ribitol concentrations and the associated O-glycosylation defect of α-dystroglycan. As the effect occurred in a mutation-dependent manner, we established a CDP-ribitol blood test to facilitate diagnosis and predict individualized treatment response. Ex vivo incubation of blood cells with ribose or ribitol restored CDP-ribitol concentrations in a patient with CRPPA LGMD. Sensitive detection of CDP-ribitol with LC-MS allows fast diagnosis of patients with severe and mild CRPPA myopathy. Ribose offers a readily testable dietary therapy for CRPPA myopathy, with possible applicability for patients with FKRP and FKTN myopathy. Evaluation of CDP-ribitol in blood is a promising tool for the evaluation and monitoring of dietary therapies for CRPPA myopathy in a patient-specific manner.

Early nutrition and gut microbiome: interrelationship between bacterial metabolism, immune system, brain structure and neurodevelopment.

Disturbances of diet during pregnancy and early postnatal life may impact colonization of gut microbiota during early life, which could influence infant health, leading to potential long-lasting consequences later in life. This is a non-systematic review that explores the recent scientific literature to provide a general perspective of this broad topic. Several studies have shown that gut microbiota composition is related to changes in metabolism, energy balance and immune system disturbances, through interaction between microbiota metabolites and host receptors by the gut-brain axis. Moreover, recent clinical studies suggest that an intestinal dysbiosis in gut microbiota may result in cognitive disorders and behavioral problems. Furthermore, recent research in the field of brain imaging focused on the study of the relationship between gut microbial ecology and large-scale brain networks, which will help to decipher the influence of the microbiome on brain function and potentially will serve to identify multiple mediators of the gut-brain axis. Thus, knowledge about optimal nutrition by modulating gut microbiota-brain axis activity, will allow a better understanding of the molecular mechanisms involved in the crosstalk between gut microbiota and the developing brain during critical windows. In addition, this knowledge will open new avenues for developing novel microbiota-modulating based diet interventions during pregnancy and early life to prevent metabolic disorders, as well as neurodevelopmental deficits and brain functional disorders.

KEYWORDS: Gut microbiota, early nutrition programing, immune system, metabolism, neurodevelopment

Two South Indian Children with KCNT1-Related Malignant Migrating Focal Seizures of Infancy - Clinical Characteristics and Outcome of Targeted Treatment with Quinidine.

KCNT1 gene encodes a sodium-gated potassium channel subunit that plays an important role in regulating excitability in neurons. Quinidine is a partial antagonist of this channel. We report the clinical characteristics of two south Indian children with KCNT1 -related epileptic encephalopathy. Both of them had very high seizure burden which were resistant to antiepileptic and dietary therapy. Pharmacological response to quinidine in these children is described. Case 1 had 30% reduction in seizure burden at 20 mg/kg/day and 80% reduction at 36 mg/kg/day; case 2 had 30% reduction at 20 mg/kg/day. Serial electrocardiography was used to monitor the cardiotoxicity. Serum quinidine levels were not measured due to nonavailability. A critical review on the current status of targeted treatment of KCNT1 -related epileptic encephalopathies with quinidine is attempted.

KEYWORDS: Epileptic encephalopathy, KCNT1, quinidine

Polyphenol intake and differentiated thyroid cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

Polyphenols are bioactive compounds with several anticarcinogenic activities; however, human data regarding associations with thyroid cancer (TC) is still negligible. Our aim was to evaluate the association between intakes of total, classes and subclasses of polyphenols and risk of differentiated TC and its main subtypes, papillary and follicular, in a European population. The European Prospective Investigation into Cancer and Nutrition cohort included 476,108 men and women from 10 European countries. During a mean follow-up of 14 years, there were 748 incident differentiated TC cases, including 601 papillary and 109 follicular tumors. Polyphenol intake was estimated at baseline using validated center/country-specific dietary questionnaires and the Phenol-Explorer database. In multivariable-adjusted Cox regression models, no association between total polyphenol and the risks of overall differentiated TC, papillary or follicular TC were found. No associations were observed either for flavonoids, phenolic acids or the rest of classes and subclasses of polyphenols. After stratification by body mass index (BMI), an inverse association between the intake of polyphenols and phenolic acids and differentiated TC risk in subjects with BMI ≥ 25 was observed. In conclusion, our study showed no associations between dietary polyphenol intake and differentiated TC risk; although further studies are warranted to investigate the potential protective associations in overweight and obese individuals.

KEYWORDS: EPIC, cohort, flavonoids, intake, polyphenols, thyroid cancer

Natural Hydrogen Sulfide Donors from Allium sp. as a Nutraceutical Approach in Type 2 Diabetes Prevention and Therapy.

Type 2 diabetes mellitus (DM) is a socially relevant chronic disease with high prevalence worldwide. DM may lead to several vascular, macrovascular, and microvascular complications (cerebrovascular, coronary artery, and peripheral arterial diseases, retinopathy, neuropathy, and nephropathy), often accelerating the progression of atherosclerosis. Dietary therapy is generally considered to be the first step in the treatment of diabetic patients. Among the current therapeutic options, such as insulin therapy and hypoglycemic drugs, in recent years, attention has been shifting to the effects and properties-that are still not completely known-of medicinal plants as valid and inexpensive therapeutic supports with limited side effects. In this review, we report the relevant effects of medicinal plants and nutraceuticals in diabetes. In particular, we paid attention to the organosulfur compounds (OSCs) present in plant extracts that due to their antioxidant, hypoglycemic, anti-inflammatory, and immunomodulatory effects, can contribute as cardioprotective agents in type 2 DM. OSCs derived from garlic ( Allium sp.), due to their properties, can represent a valuable support to the diet in type 2 DM, as outlined in this manuscript based on both in vitro and in vivo studies. Moreover, a relevant characteristic of garlic OSCs is their ability to produce the gasotransmitter H 2 S, and many of their effects can be explained by this property. Indeed, in recent years, several studies have demonstrated the relevant effects of endogenous and exogenous H 2 S in human DM, including by in vitro and in vivo experiments and clinical trials; therefore, here, we summarize the effects and the underlying molecular mechanisms of H 2 S and natural H 2 S donors.

KEYWORDS: H2S, OSCs, diabetes, garlic, inflammation, nutraceuticals, oxidative stress, phytochemicals, plants

Effect of Three Diets (Low-FODMAP, Gluten-free and Balanced) on Irritable Bowel Syndrome Symptoms and Health-Related Quality of Life.

Several studies have reported some efficacy of diets low in fermentable carbohydrates (Fermentable Oligo-, Di-, Monosaccharides and Polyols (FODMAPs)) in Irritable Bowel Syndrome (IBS). There is no evidence of its superiority compared to gluten-free and balanced diets in improving IBS patients' quality of life (QoL). The aim of this study is to assess whether different diets can improve QoL in IBS. Forty-two patients with IBS, according to Rome IV criteria, were enrolled. Low-FODMAP, gluten-free and balanced diets were proposed to each patient in the same succession. Each diet was followed for 4 weeks. The Bristol Stool Scale, the Visual Analogue Scale (VAS) for bloating and abdominal pain, and the SF12 questionnaire for health-related quality of life were applied at the beginning and at the end of each diet. Twenty-eight of the forty-two patients completed all the three diets. All the three diets reduced symptom severity, bloating and abdominal pain, and improved quality of life; 3% of patients expressed a preference for the low-FODMAP diet, 11% for the gluten-free and 86% for the balanced diet. The balanced diet improves QoL and VAS pain, provides an adequate quantity of FODMAPs and is more appreciated by patients. For these reasons, the balanced diet could be recommended to patients with irritable bowel syndrome.

KEYWORDS: FODMAPs, IBS, balanced diet, diet, diet treatment, gluten-free diet, irritable bowel syndrome, quality of life

Food Intolerances.

Food intolerances are estimated to affect up to 20% of the population but complete understanding of diagnosis and management is complicated, given presentation and non-immunological mechanisms associated vary greatly. This review aims to provide a scientific update on common food intolerances resulting in gastrointestinal and/or extra-intestinal symptoms. FODMAP sensitivity has strong evidence supporting its mechanisms of increased osmotic activity and fermentation with the resulting distention leading to symptoms in those with visceral hypersensitivity. For many of the other food intolerances reviewed including non-coeliac gluten/wheat sensitivity, food additives and bioactive food chemicals, the findings show that there is a shortage of reproducible well-designed double-blind, placebo-controlled studies, making understanding of the mechanisms, diagnosis and management difficult. Enzyme deficiencies have been proposed to result in other food sensitivities including low amine oxidase activity resulting in histamine intolerance and sucrase-isomaltase deficiency resulting in reduced tolerance to sugars and starch. Lack of reliable diagnostic biomarkers for all food intolerances result in an inability to target specific foods in the individual. As such, a trial-and-error approach is used, whereby suspected food constituents are reduced for a short-period and then re-challenged to assess response. Future studies should aim to identify biomarkers to predict response to dietary therapies.

KEYWORDS: dietary therapy, food hypersensitivity, food intolerance, functional gastrointestinal disorders

Impaired cell surface expression and digestive function of sucrase-isomaltase gene variants are associated with reduced efficacy of low FODMAPs diet in patients with IBS-D.

KEYWORDS: enzyme function, intestinal function, irritable bowel syndrome, low FODMAP diet, protein trafficking, sucrase-isomaltase gene variants

A Dietary Intervention with Reduction of Starch and Sucrose Leads to Reduced Gastrointestinal and Extra-Intestinal Symptoms in IBS Patients.

Patients with irritable bowel syndrome (IBS) exhibit low-grade inflammation and increased gut permeability. Dietary sugar has been shown to contribute to low-grade inflammation and increased gut permeability, and to correlate with gastrointestinal (GI) symptoms. The aim of the present study was to examine the effect of a starch- and sucrose-reduced diet (SSRD) on gastrointestinal (GI) and extra-intestinal symptoms in IBS. One hundred and five IBS patients, with irritable bowel syndrome-symptom severity scale (IBS-SSS) > 175, were randomized to SSRD for 4 weeks or continued ordinary eating habits. The visual analog scale for irritable bowel syndrome (VAS-IBS), IBS-SSS, and 4-day food diaries were collected at baseline and after 2 and 4 weeks. After the intervention, one-third of the patients did not fulfill the criteria for IBS/functional gastrointestinal disorder. Half of the participants changed from moderate/severe disease to no/mild disease according to IBS-SSS. Comparisons between the groups showed decreased weight and sweet cravings, and parallel decreases in total IBS-SSS and extra-intestinal IBS-SSS scores, in the intervention group compared to controls. When calculating separate extra-intestinal symptoms, belching, muscle/joint pain, urinary urgency, and tiredness were decreased after introduction of SSRD compared to controls. In conclusion, SSRD improves both GI and extra-intestinal symptoms in IBS.

KEYWORDS: diet, extra-intestinal symptoms, gastrointestinal symptoms, irritable bowel syndrome, starch, sucrose

Trust and distrust in relation to food risks in Spain: An approach to the socio-cultural representations of pregnant and breastfeeding women through the technique of free listing.

In this paper, we explore the socio-cultural representations of trust and distrust in relation to food risks among pregnant and breastfeeding women. We have conducted a study based on an analysis of cultural domains in order to understand how mothers incorporate different social meanings and explore the most important categories they use when talking about trust/distrust in relation to food. We use the technique of free listings to analyse the main shared items or elements regarding trust and distrust in food among these mothers. Through an analysis of cultural domains that refers to concepts and themes related to trust and distrust of foods that are important to these women, and through the study of shared knowledge about these domains, we examine their socio-cultural representations related to health and diet of the 65 free listings on trust and the 64 on distrust collected from mothers. The pregnant and breastfeeding women who participated in the free listings cite foods they trust or distrust based on the specific properties they perceive them to have or other characteristics related to their origin, their handling, processing and distribution. Additionally, trust/distrust often depends on the qualities they attribute to the product. This paper shows aspects of the socio-cultural representations of food risks in periods in the life cycle of women -pregnancy and breastfeeding-characterized by a risk discourse where the precautionary principle is frequently used to manage uncertainty. These results might help the development of public health campaigns as well as adapting the messages of the health authorities to the general population.

KEYWORDS: Breastfeeding, Distrust, Food risk, Free listings, Pregnancy, Trust

A Journey of Dietary Therapies for Epilepsy in Iran: Diet Restriction in the Ancient Era to the Ketogenic Diet in the Modern Period.

Epilepsy, in children, is a common neurological problem for referral to child neurology clinics. The prevalence of nonfebrile seizure in children, is estimated from 5.2 to 8.1 per 1000. Also, the prevalence of epilepsy in Iran estimated about 5 %; it means 4 million people of Iranian population live with epilepsy in Iran. Although antiseizure drugs (ASDs) are the essential treatment modalities in most children, more than 30% of epileptic children have intractable seizures or they suffer from drug adverse effects secondary to these medications. Because only a limited number of epileptic patients benefit from surgical therapy using the additional therapeutic options is inevitable. There are many available nonpharmacologic proven therapies for refractory seizures that Dietary therapy ( Ketogenic Diet) is one of the important therapeutic options in this group. In this review, we will discuss the different features of pediatric epilepsy dietary therapies (Especially the Ketogenic Diet) in Iran and also the history of epilepsy in ancient Iran, utilization, effectiveness, side effects, tolerability, and acceptability as well as ongoing and future programs.

KEYWORDS: Children, Diet Restriction, History, Ketogenic Diet

Second Asian Consensus on Irritable Bowel Syndrome.

There has been major progress in our understanding of the irritable bowel syndrome (IBS), and novel treatment classes have emerged. The Rome IV guidelines were published in 2016 and together with the growing body of Asian data on IBS, we felt it is timely to update the Asian IBS Consensus. Key opinion leaders from Asian countries were organized into 4 teams to review 4 themes: symptoms and epidemiology, pathophysiology, diagnosis and investigations, and lifestyle modifications and treatments. The consensus development process was carried out by using a modified Delphi method. Thirty-seven statements were developed. Asian data substantiate the current global viewpoint that IBS is a disorder of gut-brain interaction. Socio-cultural and environmental factors in Asia appear to influence the greater overlap between IBS and upper gastrointestinal symptoms. New classes of treatments comprising low fermentable oligo-, di-, monosacharides, and polyols diet, probiotics, non-absorbable antibiotics, and secretagogues have good evidence base for their efficacy. Our consensus is that all patients with functional gastrointestinal disorders should be evaluated comprehensively with a view to holistic management. Physicians should be encouraged to take a positive attitude to the treatment outcomes for IBS patients.

KEYWORDS: Asia, Constipation, Diarrhea, Intestines, Irritable bowel syndrome

Is Bacillus coagulans supplementation plus low FODMAP diet superior to low FODMAP diet in irritable bowel syndrome management?

The aim of this study was to assess the superiority of low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) diet plus Bacillus coagulans supplementation to low FODMAP diet alone in the reduction of irritable bowel syndrome (IBS) symptoms. In this randomized clinical trial, fifty IBS patients who met Rome IV criteria for IBS were randomly assigned to receive a low FODMAP diet plus either a probiotic or a placebo capsule for 8 weeks. Probiotic capsules contained 10 9 B. coagulans spores and 400 mg inulin, while placebo capsules consisted of 500 mg rice starch. Significant improvements were observed in abdominal pain intensity and frequency, abdominal distension, satisfaction with bowel habits, quality of life, defecation consistency, and patient-reported severity score in both groups; however, only improvement in severity score was significantly higher in probiotic group compared with placebo group. Moreover, the frequency of patients with clinical improvement in IBS-symptom severity scale (IBS-SSS) was significantly more in probiotic group compared to placebo group. Our results indicate that the addition of probiotic supplement containing B. coagulans to the low FODMAP diet might be superior to low FODMAP diet in alleviating IBS symptoms.

KEYWORDS: Bacillus coagulans, IBS, Irritable bowel syndrome, Low FODMAP diet

Blood pressure and risk of cancer in the European Prospective Investigation into Cancer and Nutrition.

Several studies have reported associations of hypertension with cancer, but not all results were conclusive. We examined the association of systolic (SBP) and diastolic (DBP) blood pressure with the development of incident cancer at all anatomical sites in the European Prospective Investigation into Cancer and Nutrition (EPIC). Hazard ratios (HR) were estimated using multivariable Cox proportional hazards models, stratified by EPIC-participating centre and age at recruitment, and adjusted for sex, education, smoking, body mass index, physical activity, diabetes and dietary (in women also reproductive) factors. The study included 307,318 men and women, with an average follow-up of 13.7 years and 39,298 incident cancers. We confirmed the expected positive association with renal cell carcinoma: HR=1.12 per 10mmHg higher SBP and HR=1.23 for DBP. We additionally found positive associations for esophageal squamous cell carcinoma (SCC): HR=1.16 (SBP), HR=1.31 (DBP), weaker for head and neck cancers: HR=1.08 (SBP), HR=1.09 (DBP) and, similarly, for skin SCC, colon cancer, post-menopausal breast cancer and uterine adenocarcinoma (AC), but not for esophageal AC, lung SCC, lung AC, or uterine endometroid cancer. We observed weak inverse associations of SBP with cervical SCC: HR=0.91 and lymphomas: HR=0.97. There were no consistent associations with cancers in other locations. Our results are largely compatible with published studies and support weak associations of blood pressure with cancers in specific locations and morphologies. This article is protected by copyright. All rights reserved.

KEYWORDS: Europe, association, cancer, cohort, epidemiology, hypertension, morphology, risk factors

Irritable bowel syndrome: how can symptoms and quality of life be improved with diet?

This article aims to review the current scientific evidence of dietary approaches to control the symptoms of irritable bowel syndrome (IBS). In the last decade, there was an important evolution in the study of the low fermentable oligo, di, mono-saccharides and polyols (FODMAP) diet (LFD). Current scientific evidence suggests a significant efficacy in the overall control of symptoms. LFD seems to be effective in improving quality of life. Recent studies suggest that LFD is effective and nutritionally well tolerated also in the long term, and longer adherence may contribute to greater effectiveness in improving depression. There is insufficient scientific evidence for the recommendation of gluten exclusion in IBS therapy, and some authors still suggest that the efficacy of this approach results from the limited ingestion of fructans. There is a promising efficacy of pre, pro, and symbiotic supplements, but there is no consensus on the most appropriate and effective strains in each case. Given the poor evidence and the pathophysiological variability of IBS, the interest of each therapeutic option should be always evaluated individually. Nevertheless, LFD is currently the dietary approach with a higher degree of scientific evidence.

Review article: biological mechanisms for symptom causation by individual FODMAP subgroups - the case for a more personalised approach to dietary restriction.

Due to the paucity of targeted therapy for irritable bowel syndrome (IBS), many patients turn to dietary modifications for symptom management. The combination of five subgroups of poorly absorbed and rapidly fermented carbohydrates-fructans, galacto-oligosaccharides, lactose, excess fructose and polyols-are thought to trigger gastrointestinal symptoms and are referred to collectively as "FODMAPs". To examine the biological plausibility and mechanisms by which foods high in specific FODMAP subgroups cause symptoms, and to use this information to explore the possibility of targeting select dietary components to allow for a more personalised approach to dietary adjustment METHODS: Recent literature was analysed via search databases including Medline, PubMed and Scopus. Lactose, fructans and galacto-oligosaccharides have strong biologic plausibility for symptom generation due to lack of hydrolases resulting in distention from osmosis and rapid fermentation. However, excess fructose and polyols may only cause symptoms in specific individuals when consumed in high doses, but this remains to be established. There is evidence to suggest that certain patient characteristics such as ethnicity may predict response to lactose, but differentiation of other subgroups is difficult prior to dietary manipulation. While some clear mechanisms of action for symptom generation have been established, further research is needed to understand which patients will respond to specific FODMAP subgroup restriction. We suggest that clinicians consider in some patients a tailored, personalised "bottom-up" approach to the low-FODMAP diet, such as dietary restriction relevant to the patients' ethnicity, symptom profile and usual dietary intake.

Canadian Association of Gastroenterology Clinical Practice Guideline for the Management of Irritable Bowel Syndrome (IBS).

Irritable bowel syndrome (IBS) is one of the most common gastrointestinal (GI) disorders, affecting about 10% of the general population globally. The aim of this consensus was to develop guidelines for the management of IBS. A systematic literature search identified studies on the management of IBS. The quality of evidence and strength of recommendations were rated according to the Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach. Statements were developed through an iterative online platform and then finalized and voted on by a multidisciplinary group of clinicians and a patient. Consensus was reached on 28 of 31 statements. Irritable bowel syndrome is diagnosed based on symptoms; serological testing is suggested to exclude celiac disease, but routine testing for C-reactive protein (CRP), fecal calprotectin or food allergies is not recommended. A trial of a low fermentable oligosaccharides, disaccharides, monosaccharides, polyols (FODMAP) diet is suggested, while a gluten-free diet is not. Psyllium, but not wheat bran, supplementation may help reduce symptoms. Alternative therapies such as peppermint oil and probiotics are suggested, while herbal therapies and acupuncture are not. Cognitive behavioural therapy and hypnotherapy are suggested psychological therapies. Among the suggested or recommended pharmacological therapies are antispasmodics, certain antidepressants, eluxadoline, lubiprostone, and linaclotide. Loperamide, cholestyramine and osmotic laxatives are not recommended for overall IBS symptoms. The nature of the IBS symptoms (diarrhea-predominant or constipation-predominant) should be considered in the choice of pharmacological treatments. Patients with IBS may benefit from a multipronged, individualized approach to treatment, including dietary modifications, psychological and pharmacological therapies.

KEYWORDS: Clinical practice guidelines, Constipation, Diarrhea, Irritable bowel syndrome

Reproductive and lifestyle factors and circulating sRANKL and OPG concentrations in women: Results from the EPIC cohort.

Except for a documented increase in osteoprotegerin (OPG) concentrations with older age, data on determinants of soluble Receptor Activator of Nuclear Factor κB (sRANKL) and OPG concentrations in women are limited. We evaluated reproductive and lifestyle factors as potential sources of variation in circulating sRANKL and OPG concentrations in pre- and postmenopausal women. This study includes 2016 controls (n=1552 postmenopausal, n=757 using postmenopausal hormone therapy (PMH)) from a breast cancer case-control study nested in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Serum sRANKL was measured using an enzyme-linked immunosorbent assay, serum OPG using an electrochemiluminescent assay. Generalized linear models were used to evaluate associations between these analytes and reproductive and lifestyle factors. Older age at blood collection was associated with lower sRANKL concentrations in postmenopausal women and higher OPG concentrations in all women. Longer duration of OC use among premenopausal women and postmenopausal PMH users was associated with higher OPG. In postmenopausal non-PMH users, sRANKL concentrations were lower with longer duration of OC use and current (vs. never) smoking. sRANKL concentrations were higher among women with higher BMI. The evaluated factors accounted for 12% of the variation in sRANKL concentrations and 21% of the variation in OPG concentrations. Circulating sRANKL and OPG concentrations are minimally impacted by hormone-related factors in pre- and postmenopausal women. This study suggests circulating concentrations of sRANKL and OPG are unlikely to be strongly modified by hormone-related reproductive and lifestyle factors.

The impact of dietary fermentable carbohydrates on a postinflammatory model of irritable bowel syndrome.

A low fermentable carbohydrate (FODMAP) diet is used in quiescent inflammatory bowel disease when irritable bowel syndrome-like symptoms occur. There is concern that the diet could exacerbate inflammation by modifying microbiota and short-chain fatty acid (SCFA) production. We examined the effect of altering dietary FODMAP content on inflammation in preclinical inflammatory models. C57BL/6 mice were given 3% dextran sodium sulfate (DSS) in drinking water for 5 days and recovered for 3 weeks, or 5 days. Following recovery, DSS-treated or control mice were randomized to 2-week low- or high-FODMAP diets. Diets mimicked human consumption containing fructose, sorbitol, galacto-oligosaccharide, and fructan. Colons were assessed for myeloperoxidase (MPO) activity and histological damage. Supernatants were generated for perforated patch-clamp recordings and cytokine measurement. Cecum contents were analyzed for microbiota, SCFA, and branched-chain fatty acids (BCFA). Data were analyzed by two-way ANOVA with Bonferroni. Inflammatory markers were higher in the positive-control compared with negative-control and postinflammatory groups, but no differences occurred between the two diets within each treatment, or the perforated patch-clamp recordings. Microbiota clustered mainly based on DSS exposure. No difference in SCFA content occurred. Higher total BCFA occurred with the low-FODMAP diet in positive-control and postinflammatory groups. In this preclinical study, reducing dietary FODMAPs did not exacerbate nor mitigate inflammation. Microbiota profile changes were largely driven by inflammation rather than diet. Low FODMAP intake caused a shift toward proteolytic fermentation following inflammation.

KEYWORDS: di-, dietary therapy, fermentable oligo-, fermentation patterns, inflammation, mono-saccharides and polyols