Psyllium reduces inulin-induced colonic gas production in IBS: MRI and in vitro fermentation studies.

OBJECTIVE: Health-promoting dietary fibre including inulin often triggers gastrointestinal symptoms in patients with IBS, limiting their intake. Our aim was to test if coadministering psyllium with inulin would reduce gas production. DESIGN: A randomised, four-period, four-treatment, placebo-controlled, crossover trial in 19 patients with IBS. Subjects ingested a 500 mL test drink containing either inulin 20 g, psyllium 20 g, inulin 20 g+ psyllium 20 g or dextrose 20 g (placebo). Breath hydrogen was measured every 30 min with MRI scans hourly for 6 hours. Faecal samples from a subset of the patients with IBS were tested using an in vitro fermentation model. Primary endpoint was colonic gas assessed by MRI. RESULTS: Colonic gas rose steadily from 0 to 6 hours, with inulin causing the greatest rise, median (IQR) AUC(0-360 min) 3145 (848-6502) mL·min. This was significantly reduced with inulin and psyllium coadministration to 618 (62-2345) mL·min (p=0.02), not significantly different from placebo. Colonic volumes AUC(0-360 min) were significantly larger than placebo for both inulin (p=0.002) and inulin and psyllium coadministration (p=0.005). Breath hydrogen rose significantly from 120 min after inulin but not psyllium; coadministration of psyllium with inulin delayed and reduced the maximum increase, AUC(0-360 min) from 7230 (3255-17910) ppm·hour to 1035 (360-4320) ppm·hour, p=0.007.Fermentation in vitro produced more gas with inulin than psyllium. Combining psyllium with inulin did not reduce gas production. CONCLUSIONS: Psyllium reduced inulin-related gas production in patients with IBS but does not directly inhibit fermentation. Whether coadministration with psyllium increases the tolerability of prebiotics in IBS warrants further study. TRIAL REGISTRATION NUMBER: NCT03265002.

Role of the Microbiome in Regulating Bone Metabolism and Susceptibility to Osteoporosis.

The human microbiota functions at the interface between diet, medication-use, lifestyle, host immune development and health. It is therefore closely aligned with many of the recognised modifiable factors that influence bone mass accrual in the young, and bone maintenance and skeletal decline in older populations. While understanding of the relationship between micro-organisms and bone health is still in its infancy, two decades of broader microbiome research and discovery supports a role of the human gut microbiome in the regulation of bone metabolism and pathogenesis of osteoporosis as well as its prevention and treatment. Pre-clinical research has demonstrated biological interactions between the microbiome and bone metabolism. Furthermore, observational studies and randomized clinical trials have indicated that therapeutic manipulation of the microbiota by oral administration of probiotics may influence bone turnover and prevent bone loss in humans. In this paper, we summarize the content, discussion and conclusions of a workshop held by the Osteoporosis and Bone Research Academy of the Royal Osteoporosis Society in October, 2020. We provide a detailed review of the literature examining the relationship between the microbiota and bone health in animal models and in humans, as well as formulating the agenda for key research priorities required to advance this field. We also underscore the potential pitfalls in this research field that should be avoided and provide methodological recommendations to facilitate bridging the gap from promising concept to a potential cause and intervention target for osteoporosis.

ß-Galactooligosaccharide in Conjunction With Low FODMAP Diet Improves Irritable Bowel Syndrome Symptoms but Reduces Fecal Bifidobacteria.

INTRODUCTION: The low FODMAP diet (LFD) reduces symptoms and bifidobacteria in irritable bowel syndrome (IBS). ß-galactooligosaccharides (B-GOS) may reduce the symptoms and increase bifidobacteria in IBS. We investigated whether B-GOS supplementation alongside the LFD improves IBS symptoms while preventing the decline in bifidobacteria. METHODS: We performed a randomized, placebo-controlled, 3-arm trial of 69 Rome III adult patients with IBS from secondary care in the United Kingdom. Patients were randomized to a sham diet with placebo supplement (control) or LFD supplemented with either placebo (LFD) or 1.4 g/d B-GOS (LFD/B-GOS) for 4 weeks. Gastrointestinal symptoms, fecal microbiota (fluorescent in situ hybridization and 16S rRNA sequencing), fecal short-chain fatty acids (gas-liquid chromatography) and pH (probe), and urine metabolites (H NMR) were analyzed. RESULTS: At 4 weeks, adequate symptom relief was higher in the LFD/B-GOS group (16/24, 67%) than in the control group (7/23, 30%) (odds ratio 4.6, 95% confidence interval: 1.3-15.6; P = 0.015); Bifidobacterium concentrations (log10 cells/g dry weight) were not different between LFD and LFD/B-GOS but were lower in the LFD/B-GOS (9.49 [0.73]) than in the control (9.77 [0.41], P = 0.018). A proportion of Actinobacteria was lower in LFD (1.9%, P = 0.003) and LFD/B-GOS (1.8%, P < 0.001) groups than in the control group (4.2%). Fecal butyrate was lower in the LFD (387.3, P = 0.028) and LFD/B-GOS (346.0, P = 0.007) groups than in the control group (609.2). DISCUSSION: The LFD combined with B-GOS prebiotic produced a greater symptom response than the sham diet plus placebo, but addition of 1.4 g/d B-GOS did not prevent the reduction of bifidobacteria. The LFD reduces fecal Actinobacteria and butyrate thus strict long-term use should not be advised.

Volatile Organic Compounds in Feces Associate With Response to Dietary Intervention in Patients With Irritable Bowel Syndrome.

BACKGROUND & AIMS: Dietary interventions are effective in management of patients with irritable bowel syndrome (IBS), although responses vary. We investigated whether fecal levels of volatile organic compounds (VOCs) associate with response to dietary interventions in patients with IBS. METHODS: Adults who fulfilled the Rome III criteria for IBS were recruited to a 2x2 factorial randomized controlled trial. Patients were randomly assigned to a group counselled to follow a diet low in fructans, galacto-oligosaccharides, lactose, fructose, and polyols (low-FODMAP diet, n = 46) or a group that received placebo dietary advice (sham diet, n = 47) for 4 weeks. Patients from each group were also given either a multi-strain probiotic or placebo supplement. Response was defined as a reduction of 50 points or more on the validated IBS symptom scoring system. Fecal samples were collected from participants at baseline and end of the 4-week study period; VOCs were analyzed by a gas-chromatography sensor device. VOC profiles were determined using a pipeline involving wavelet transformation followed by feature selection based on random forest. A partial least squares classifier was constructed to classify VOC profiles by response and accuracies were determined using 10-fold cross-validation. RESULTS: Data from 93 patients who completed the study (63 female) were used in the final analysis. More patients responded to the low-FODMAP diet (37/46, 80%) than the sham diet (21/47, 45%) (P < .001), but there was no difference in response between patients given the probiotic (31/49, 63%) vs the placebo (27/44, 61%) (P = .850), with no interaction between the diet and supplement interventions. At baseline, VOC profiles contained 15 features that classified response to the low-FODMAP diet with a mean accuracy of 97% (95% CI, 96%-99%) and 10 features that classified response to probiotic with a mean accuracy of 89% (95% CI, 86%-92%). End of treatment models achieved similar predictive powers and accuracies. CONCLUSION: Fecal VOC profiling is a low cost, non-invasive tool that might be used to predict responses of patients with IBS to low-FODMAP diet and probiotics and identify their mechanisms of action. ISRCTN registry no: 02275221.

Irritable bowel syndrome and diet: where are we in 2018?

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.

Beyond Sodium, Phosphate and Potassium: Potential Dietary Interventions in Kidney Disease.

People with kidney disease are advised to restrict individual nutrients, such as sodium, potassium, and phosphate, in line with current best practice guidelines. However, there is limited evidence to support the efficacy of single nutrient strategies, and compliance remains a challenge for clinicians to overcome. Many factors contribute to poor compliance with dietary prescriptions, including conflicting priorities for single nutrient restriction, the arduous self-monitoring required, and the health-related knock-on effects resulting from targeting these nutrients in isolation. This paper reviews the evidence base for the overall pattern of eating as a potential tool to deliver a diet intervention in which all the nutrients and foods work cumulatively and synergistically to improve clinical outcomes. These interventions may assist in kidney disease management and overcome these innate challenges that single nutrient interventions possess. Healthy dietary patterns are typically plant-based and lower in sodium and animal proteins. These patterns may have numerous mechanistic benefits for cardiovascular health in kidney disease, most notably through the increase in fruit, vegetables, and plant-based protein, as well as improved gut health through the increase in dietary fiber. The evidence to date on optimal dietary patterns points toward use of a predominantly plant-based diet, and suggests its adoption may improve clinical outcomes in dialysis patients. However, clinical trials are needed to determine whether these diet interventions are feasible, safe, and effective in this patient population.

Fermentable oligosaccharide, disaccharide, monosaccharide and polyol content of foods commonly consumed by ethnic minority groups in the United Kingdom.

Dietary restriction of fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs) is an effective management approach for functional bowel disorders; however, its application is limited by the paucity of food composition data available for ethnic minority groups. The aim was to identify and measure the FODMAP content of these commonly consumed foods. According to their perceived importance to clinical practise, the top 20 ranked foods underwent FODMAP analysis using validated analytical techniques (total fructans, Megazyme hexokinase (HK) assay; all others, high-performance liquid chromatography (HPLC) with evaporative light scattering detectors). Of the 20 foods analysed, five were identified as significant sources of at least one FODMAP. Fructans and galacto-oligosaccharides were the major FODMAPs in these foods, including channa dal (0.13 g/100 g; 0.36 g/100 g), fenugreek seeds (1.11 g/100 g; 1.27 g/100 g), guava (0.41 g/100 g; not detected), karela (not detected; 1.12 g/100 g) and tamarind (2.35 g/100 g; 0.02 g/100 g). Broadening the availability of FODMAP composition data will increase the cultural application of low FODMAP dietary advice.

Left ventricular global longitudinal strain is associated with cardiovascular risk factors and arterial stiffness in chronic kidney disease.

BACKGROUND: Global longitudinal strain (GLS) has emerged as a superior method for detecting left ventricular (LV) systolic dysfunction compared to ejection fraction (EF) on the basis that it is less operator dependent and more reproducible. The 2-dimensional strain (2DS) method is easily measured and integrated into a standard echocardiogram. This study aimed to determine the relationship between GLS and traditional and chronic kidney disease (CKD)-related risk factors of cardiovascular disease (CVD) in patients with CKD. METHODS: A cross sectional study of patients with moderate CKD stages 3 and 4 (n = 136). Clinical characteristics, anthropometric, biochemical data including markers of inflammation [C-reactive protein (CRP)], uremic toxins [indoxyl sulphate (IS), p-cresyl sulphate (PCS)], and arterial stiffness [pulse wave velocity (PWV)] were measured. Inducible ischemia was detected using exercise stress echocardiogram. GLS was determined from 3 standard apical views using 2-dimensional speckle tracking and EF was measured using Simpson's rule. Associations between GLS and traditional and CKD-related risk factors were explored using multivariate models. RESULTS: The study population parameters included: age 59.4 ± 9.8 years, 58 % male, estimated glomerular filtration rate (eGFR) 44.4 ± 10.1 ml/min/1.73 m(2), GLS -18.3 ± 3.6 % and EF 65.8 % ± 7.8 %. This study demonstrated that GLS correlated with diabetes (r = 0.21, p = 0.01), history of heart failure (r = 0.20, p = 0.01), free IS (r = 0.24, p = 0.005) free PCS (r = 0.23, p = 0.007), body mass index (BMI) (r = 0.28, p < 0.001), and PWV (r = 0.24, p = 0.009). Following adjustment for demographic, baseline co-morbidities and laboratory parameters, GLS was independently associated with free IS, BMI and arterial stiffness (R(2) for model = .30, p < 0.0001). CONCLUSIONS: In the CKD cohort, LV systolic function assessed using GLS was associated with uremic toxins, obesity and arterial stiffness.

The Kidney-Gut Axis: Implications for Nutrition Care.

There is increasing clinical evidence that patients with chronic kidney disease (CKD) have a distinctly dysbiotic intestinal bacterial community, termed the gut microbiota, which in turn drives a cascade of metabolic abnormalities, including uremic toxin production, inflammation, and immunosuppression, that ultimately promotes progressive kidney failure and cardiovascular disease. As the gut microbiota is intimately influenced by diet, the discovery of the kidney-gut axis has created new therapeutic opportunities for nutritional intervention. This review discusses the metabolic pathways linking dysbiotic gut microbiota with adverse health outcomes in patients with CKD, as well as novel therapeutic strategies for targeting these pathways involving dietary protein, fiber, prebiotics, probiotics, and synbiotics. These emerging nutritional interventions may ultimately lead to a paradigm shift in the conventional focus of dietary management in CKD.

Prevalence of Phosphorus-Based Additives in the Australian Food Supply: A Challenge for Dietary Education?

OBJECTIVE: Phosphorus-based food additives may pose a significant risk in chronic kidney disease given the link between hyperphosphatemia and cardiovascular disease. The objective of the study was to determine the prevalence of phosphorus-based food additives in best-selling processed grocery products and to establish how they were reported on food labels. DESIGN: A data set of 3000 best-selling grocery items in Australia across 15 food and beverage categories was obtained for the 12 months ending December 2013 produced by the Nielsen Company's Homescan database. The nutrition labels of the products were reviewed in store for phosphorus additives. The type of additive, total number of additives, and method of reporting (written out in words or as an E number) were recorded. MAIN OUTCOME MEASURES: Presence of phosphorus-based food additives, number of phosphorus-based food additives per product, and the reporting method of additives on product ingredient lists. RESULTS: Phosphorus-based additives were identified in 44% of food and beverages reviewed. Additives were particularly common in the categories of small goods (96%), bakery goods (93%), frozen meals (75%), prepared foods (70%), and biscuits (65%). A total of 19 different phosphorus additives were identified across the reviewed products. From the items containing phosphorus additives, there was a median (minimum-maximum) of 2 (1-7) additives per product. Additives by E number (81%) was the most common method of reporting. CONCLUSION: Phosphorus-based food additives are common in the Australian food supply. This suggests that prioritizing phosphorus additive education may be an important strategy in the dietary management of hyperphosphatemia. Further research to establish a database of food items containing phosphorus-based additives is warranted.

SYNbiotics Easing Renal failure by improving Gut microbiologY (SYNERGY): a protocol of placebo-controlled randomised cross-over trial.

BACKGROUND: Emerging evidence suggests modulating the microbiota in the large bowel of patients with chronic kidney disease (CKD) through pre- and/probiotic supplementation may inhibit the development of key nephrovascular toxins. To date, quality intervention trials investigating this novel treatment in CKD are lacking. The aim of SYNERGY is to assess the effectiveness of synbiotics (co-administration of pre- and probiotics) as a potential treatment targeting the synthesis of uremic toxins, specifically, indoxyl sulphate (IS) and p-cresyl sulphate (PCS). METHODS/DESIGN: Thirty-seven patients with moderate to severe CKD (Stage IV and V, pre-dialysis) will be recruited to a double-blind, placebo-controlled, randomised cross-over trial. Patients will be provided with synbiotic therapy or placebo for 6 weeks, with a 4 week washout before cross-over. The primary outcome is serum IS, total and free (unbound) concentrations, measured using ultra-performance liquid chromatography. Secondary outcomes include serum PCS, total and free (unbound) concentrations; cardiovascular risk, measured by serum lipopolysaccharides, serum trimethylamine-N-oxide (TMAO) and inflammation and oxidative stress markers; kidney damage, measured by 24 hour proteinuria and albuminuria, estimated glomerular filtration rate and renal tubule damage (urinary kidney injury molecule-1); patients' self assessed quality of life; and gastrointestinal symptoms. In addition, the effects on the community structure of the stool microbiota will be explored in a subset of patients to validate the mechanistic rationale underpinning the synbiotic therapy. DISCUSSION: IS and PCS are two novel uremic toxins implicated in both cardiovascular disease (CVD) and progression of CKD. Preliminary studies indicate that synbiotic therapy maybe a promising strategy when considering a targeted, tolerable and cost-efficient therapy for lowering serum IS and PCS concentrations. This trial will provide high quality 'proof-of-concept' data to elucidate both the efficacy of synbiotic therapy for lowering the toxins and whether reductions in serum IS and PCS translate into clinical benefits. Considering the potential of pre- and probiotics to not only shift toxin levels, but to also impede CVD and CKD progression, SYNERGY will provide vital insight into the effectiveness of this innocuous nutritional therapy. TRIAL REGISTRATION: Universal Trial Number: U1111-1142-4363. Australian New Zealand Clinical Trials Registry Number: ACTRN12613000493741, date registered: 2nd May 2013.

Faecal and urine metabolites, but not gut microbiota, may predict response to low FODMAP diet in irritable bowel syndrome.

BACKGROUND: The low FODMAP diet (LFD) leads to clinical response in 50%-80% of patients with irritable bowel syndrome (IBS). It is unclear why only some patients respond. AIMS: To determine if differences in baseline faecal microbiota or faecal and urine metabolite profiles may separate clinical responders to the diet from non-responders allowing predictive algorithms to be proposed. METHODS: We recruited adults fulfilling Rome III criteria for IBS to a blinded randomised controlled trial. Patients were randomised to sham diet with a placebo supplement (control) or LFD supplemented with either placebo (LFD) or 1.8 g/d B-galactooligosaccharide (LFD/B-GOS), for 4 weeks. Clinical response was defined as adequate symptom relief at 4 weeks after the intervention (global symptom question). Differences between responders and non-responders in faecal microbiota (FISH, 16S rRNA sequencing) and faecal (gas-liquid chromatography, gas-chromatography mass-spectrometry) and urine (1 H NMR) metabolites were analysed. RESULTS: At 4 weeks, clinical response differed across the 3groups with adequate symptom relief of 30% (7/23) in controls, 50% (11/22) in the LFD group and 67% (16/24) in the LFD/B-GOS group (p = 0.048). In the control and the LFD/B-GOS groups, microbiota and metabolites did not separate responders from non-responders. In the LFD group, higher baseline faecal propionate (sensitivity 91%, specificity 89%) and cyclohexanecarboxylic acid esters (sensitivity 80%, specificity 78%), and urine metabolite profile (Q2 0.296 vs. randomised -0.175) predicted clinical response. CONCLUSIONS: Baseline faecal and urine metabolites may predict response to the LFD.

Fecal Microbial Composition and Predicted Functional Profile in Irritable Bowel Syndrome Differ between Subtypes and Geographical Locations.

Increasing evidence suggests a microbial pathogenesis in irritable bowel syndrome (IBS) but the relationship remains elusive. Fecal DNA samples from 120 patients with IBS, 82 Mexican (IBS-C: n = 33, IBS-D: n = 24, IBS-M: n = 25) and 38 British (IBS-C: n = 6, IBS-D: n = 27, IBS-M: n = 5), were available for analysis using 16S rRNA gene sequencing. Firmicutes (mean: 82.1%), Actinobacteria (10.2%), and Bacteroidetes (4.4%) were the most abundant taxa. The analysis of all samples (n = 120), and females (n = 94) only, showed no significant differences in bacterial microbiota, but the analysis of Mexican patients (n = 82) showed several differences in key taxa (e.g., Faecalibacterium) among the different IBS subtypes. In IBS-D there were significantly higher Bacteroidetes in British patients (n = 27) than in Mexican patients (n = 24), suggesting unique fecal microbiota signatures within the same IBS subtype. These differences in IBS-D were also observed at lower phylogenetic levels (e.g., higher Enterobacteriaceae and Streptococcus in Mexican patients) and were accompanied by differences in several alpha diversity metrics. Beta diversity was not different among IBS subtypes when using all samples, but the analysis of IBS-D patients revealed consistent differences between Mexican and British patients. This study suggests that fecal microbiota is different between IBS subtypes and also within each subtype depending on geographical location.

Long-term personalized low FODMAP diet improves symptoms and maintains luminal Bifidobacteria abundance in irritable bowel syndrome.

BACKGROUND: Short-term trials demonstrate the low FODMAP diet improves symptoms of irritable bowel syndrome (IBS) but impacts nutrient intake and the gastrointestinal microbiota. The aim of this study was to investigate clinical symptoms, nutrient intake, and microbiota of patients with IBS 12 months after starting a low FODMAP diet. METHODS: Participants enrolled in a previous short-term clinical trial and who had been through structured FODMAP restriction, reintroduction, and personalization were invited to participate in a follow-up study at one time point at 12 months. Gastrointestinal symptoms, stool output, dietary intake, and quality of life were recorded. Stool samples were collected and analyzed for microbiota (qPCR) and short-chain fatty acids (SCFA). Data were compared with baseline (prior to any intervention in the original clinical trial) using non-parametric statistics. KEY RESULTS: Eighteen participants were included in the study. Adequate relief of symptoms occurred in 5/18 (28%) at baseline and increased to 12/18 (67%) following long-term personalized low FODMAP diet (p = 0.039). There was a reduction in IBS-SSS total score between baseline (median 227, IQR 99) and long term (154, 89; p < 0.001). Bifidobacteria abundance was not different between baseline (median 9.29 log10 rRNA genes/g, IQR 1.45) and long term (9.20 log10 rRNA genes/g, 1.41; p = 0.766, q = 0.906); however, there were lower concentrations of total SCFA, acetate, propionate, and butyrate. CONCLUSIONS: In this long-term analysis, two thirds of patients reported adequate relief of symptoms after 12 months of personalized low FODMAP diet that did not result in differences from baseline in Bifidobacteria. FODMAP reintroduction and personalization may normalize some of the effects of short-term FODMAP restriction.

The impact of almonds and almond processing on gastrointestinal physiology, luminal microbiology, and gastrointestinal symptoms: a randomized controlled trial and mastication study.

BACKGROUND: Almonds contain lipid, fiber, and polyphenols and possess physicochemical properties that affect nutrient bioaccessibility, which are hypothesized to affect gut physiology and microbiota. OBJECTIVES: To investigate the impact of whole almonds and ground almonds (almond flour) on fecal bifidobacteria (primary outcome), gut microbiota composition, and gut transit time. METHODS: Healthy adults (n = 87) participated in a parallel, 3-arm randomized controlled trial. Participants received whole almonds (56 g/d), ground almonds (56 g/d), or an isocaloric control in place of habitual snacks for 4 wk. Gut microbiota composition and diversity (16S rRNA gene sequencing), SCFAs (GC), volatile organic compounds (GC-MS), gut transit time (wireless motility capsule), stool output and gut symptoms (7-d diary) were measured at baseline and endpoint. The impact of almond form on particle size distribution (PSD) and predicted lipid release was measured (n = 31). RESULTS: Modified intention-to-treat analysis was performed on 79 participants. There were no significant differences in mean ± SD abundance of fecal bifidobacteria after consumption of whole almonds (8.7% ± 7.7%), ground almonds (7.8% ± 6.9%), or control (13.0% ± 10.2%; q = 0.613). Consumption of almonds (whole and ground pooled) resulted in higher mean ± SD butyrate (24.1 ± 15.0 µmol/g) than control (18.2 ± 9.1 µmol/g; P = 0.046). There was no effect of almonds on gut microbiota at the phylum level or diversity, gut transit time, stool consistency, or gut symptoms. Almond form (whole compared with ground) had no effect on study outcomes. Ground almonds resulted in significantly smaller PSD and higher mean ± SD predicted lipid release (10.4% ± 1.8%) than whole almonds (9.3% ± 2.0%; P = 0.017). CONCLUSIONS: Almond consumption has limited impact on microbiota composition but increases butyrate in adults, suggesting positive alterations to microbiota functionality. Almonds can be incorporated into the diet to increase fiber consumption without gut symptoms.This trial was registered at clinicaltrials.gov as NCT03581812.

Food additive emulsifiers: a review of their role in foods, legislation and classifications, presence in food supply, dietary exposure, and safety assessment.

Food additive intakes have increased with the increase in "ultra-processed" food consumption. Food additive emulsifiers have received particular research attention in recent years due to preliminary evidence of adverse gastrointestinal and metabolic health effects. In this review, the use of emulsifiers as food additives is discussed, and the current estimations of exposure to, and safety of, emulsifiers are critically assessed. Food additive emulsifier research is complicated by heterogeneity in additives considered to be emulsifiers and labelling of them on foods globally. Major limitations exist in estimating food additive emulsifier exposure, relating predominantly to a lack of available food occurrence and concentration data. Development of brand-specific food additive emulsifier databases are crucial to accurately estimating emulsifier exposure. Current research on the health effects of food additive emulsifiers are limited to in vitro and murine studies and small, acute studies in humans, and future research should focus on controlled human trials of longer duration.

Dietary fibre in gastrointestinal health and disease.

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.

Food Additive Emulsifiers and Their Impact on Gut Microbiome, Permeability, and Inflammation: Mechanistic Insights in Inflammatory Bowel Disease.

The global burden of inflammatory bowel disease [IBD] has increased over the 21st century. Despite multiple studies investigating the pathogenesis of IBD, the causative mechanisms pertaining to its increased prevalence remain unclear. There is growing evidence that aspects of a 'Western diet' increase the risk of developing IBD. More recently, evidence implicating dietary emulsifiers has accumulated, with ecological studies showing a positive correlation between inflammatory bowel disease and emulsifier consumption. Further to these, cell and animal studies have demonstrated plausible mechanisms by which dietary emulsifiers may contribute to IBD pathogenesis through mechanisms including: promotion of pro-inflammatory intestinal microbiota; disruption of mucus architecture; increased intestinal permeability; activation of inflammatory pathways; and disruption of the cell cycle. This review critically analyses the current evidence for these mechanisms that may be of pathological relevance to IBD, evaluates recent dietary trials, acknowledges the challenges of dietary intervention studies, and gives an overview of ongoing and future clinical trials in this important area.

Nopal fiber (Opuntia ficus-indica) improves symptoms in irritable bowel syndrome in the short term: a randomized controlled trial.

BACKGROUND: Clinical guidelines provide limited and conflicting recommendations regarding dietary fiber supplementation in irritable bowel syndrome (IBS). Nopal (Opuntia ficus-indica) is a cactus plant fiber containing both insoluble and soluble fibers that may have therapeutic potential in IBS. Our aim was to evaluate the dose-response effect of extracted nopal fiber powder on symptoms in IBS. METHODS: We performed a 4-arm, double-blind, parallel, randomized controlled trial in 60 patients fulfilling Rome IV criteria for IBS. Patients were randomized and blindly allocated to receive either nopal fiber (10, 20, or 30 g/day) or placebo (30 g/day dextrose) for one week and to keep their usual diet. Symptom severity (Global Symptom Question, IBS-SSS, Gastrointestinal Symptom Rating Scale), stool frequency and consistency (Bristol Stool Form Scale), breath hydrogen response, and stool short-chain fatty acids (SCFA) were measured at baseline and follow-up. KEY RESULTS: Significantly more patients reported adequate relief of symptoms after 20 g/day (87%, p = 0.008) and 30 g/day (80%, p = 0.025) of nopal fiber compared to placebo (33%). More patients receiving 20 g/day nopal fiber (67%) had a > 50% reduction in IBS-SSS compared to placebo (20%, p = 0.027), whereas the 30 g/day dose induced more loose stools (p = 0.027). Response rates were similar among IBS subtypes. There were no differences in breath hydrogen or stool SCFA between groups. CONCLUSIONS AND INFERENCES: Nopal fiber supplementation at doses of 20 and 30 g/day was associated with short-term improvement in IBS symptoms, warranting a fully powered clinical trial of longer duration with symptomatic, physiological, and microbiological endpoints.

Emulsifiers Impact Colonic Length in Mice and Emulsifier Restriction is Feasible in People with Crohn's Disease.

There is an association between food additive emulsifiers and the prevalence of Crohn's disease. This study aimed to investigate: (i) the effect of different classes of emulsifiers on markers of intestinal inflammation in mice and (ii) the feasibility, nutritional adequacy and symptom impact of restricting all emulsifier classes in Crohn's disease. Mice were exposed to different classes of emulsifiers (carboxymethycellose, polysorbate-80, soy lecithin, gum arabic) in drinking water for 12-weeks, after which markers of inflammation and metabolism were measured. A low emulsifier diet was developed to restrict all classes of emulsifiers and its feasibility measured over 14-days in 20 participants with stable Crohn's disease. Crohn's disease-related symptoms, disease control, body weight and composition, nutrient intake and food-related quality of life (QoL) were measured. All emulsifiers resulted in lower murine colonic length compared with control (mean 9.5 cm (SEM 0.20)), but this only reached significance for polysorbate-80 (8.2 cm (0.34), p = 0.024) and carboxymethylcellulose (8.0 cm (0.35), p = 0.013). All 20 participants completed the feasibility study. The frequency of consuming emulsifier-containing foods decreased by 94.6% (SD 10.3%). Food-related QoL improved between habitual (median 81.5 (IQR 25.0)) and low emulsifier diet (90.0 (24.0), p = 0.028). Crohn's disease-related symptoms reduced (median 3.0 (IQR 5.3) vs. 1.4 (3.9), p = 0.006), and disease control scores improved (13.5 (IQR 6.0) vs. 15.5 (IQR 3.0), p = 0.026). A range of emulsifiers may influence intestinal inflammation in mice, and dietary restriction of emulsifiers is feasible. Trials investigating the efficacy of a low emulsifier diet in Crohn's disease are warranted.