Nature of the evidence base and approaches to guide nutrition interventions for individuals: a position paper from the Academy of Nutrition Sciences.

This Position Paper from the Academy of Nutrition Sciences is the third in a series which describe the nature of the scientific evidence and frameworks that underpin nutrition recommendations for health. This paper focuses on evidence which guides the application of dietary recommendations for individuals. In some situations, modified nutrient intake becomes essential to prevent deficiency, optimise development and health, or manage symptoms and disease progression. Disease and its treatment can also affect taste, appetite and ability to access and prepare foods, with associated financial impacts. Therefore, the practice of nutrition and dietetics must integrate and apply the sciences of food, nutrition, biology, physiology, behaviour, management, communication and society to achieve and maintain human health. Thus, there is huge complexity in delivering evidence-based nutrition interventions to individuals. This paper examines available frameworks for appraising the quality and certainty of nutrition research evidence, the development nutrition practice guidelines to support evidence implementation in practice and the influence of other sources of nutrition information and misinformation. The paper also considers major challenges in applying research evidence to an individual and suggests consensus recommendations to begin to address these challenges in the future. Our recommendations target three groups; those who deliver nutrition interventions to individuals, those funding, commissioning or undertaking research aimed at delivering evidence-based nutrition practice, and those disseminating nutritional information to individuals.

Teaching and assessment of communication skills in dietetics: a scoping review.

BACKGROUND: Communication is a core element of dietetic practice, and although communication skills are a prominent feature of dietetic curricula, research suggests a need for more consistent approaches. The evidence on how communication skills are taught and assessed in dietetics has not been synthesised leaving uncertainty about best practice. This scoping review aimed to examine and map the research literature relating to the teaching and assessment of communication skills in dietetics. METHODS: The review was conducted in accordance with the Joanna Briggs Institute (JBI) methodology for scoping reviews. Five electronic databases, two theses databases and eight conference proceedings were systematically searched for research on how communication skills are taught and assessed in dietetics. The search had no geographical or time limits. Studies were independently screened by two authors, summarised thematically using the Kirkpatrick Model and narratively synthesised. RESULTS: The 45 included studies were organised thematically into three categories: (i) the inclusion of communication skills education in dietetics, suggesting that dietitians have variable experiences; (ii) approaches to teaching communication skills in dietetics, characterised predominantly by a move away from didactic approaches in favour of experiential opportunities for learning such as simulation; and (iii) assessment of communication skills in dietetics, including the use of both dietetic-specific and generic tools. CONCLUSIONS: The included studies demonstrate that although a variety of teaching strategies are used in the development of communication skills in dietetics, there is potential for more robust evaluation and more diverse approaches to support dietetic educators to prepare the dietetic workforce.

Probiotics in irritable bowel syndrome and inflammatory bowel disease: review of mechanisms and effectiveness.

PURPOSE OF REVIEW: The gastrointestinal (GI) microbiome has been implicated in the pathogenesis of inflammatory bowel disease (IBD) and has been linked with irritable bowel syndrome (IBS). The aim of this article is to critically review the emerging evidence for the mechanisms and effectiveness of probiotics in the management of these conditions. RECENT FINDINGS: The GI microbiome is strongly influenced by ageing, diet and disease. Probiotics may confer health effects to the host by modulating the metabolic activities of the microbiome to propagate anti-inflammatory effects and reinforce the intestinal barrier, and are considered to be safe to use. Many short-term studies have demonstrated the effectiveness of probiotics overall in IBS, with meta-analyses demonstrating efficacy across specific strains albeit with relatively small effect sizes. Within IBD, some probiotics appear to offer clinical benefit in ulcerative colitis but strain-specific effects are unclear. Evidence for the use of probiotics in Crohn's disease remains limited. SUMMARY: Probiotics offer considerable potential for the management of IBS and possibly in IBD, however, any benefits conferred appear to be strain-specific. High quality trials of specific probiotics in IBS and IBD, as well as laboratory investigations of their mechanism of action, are required in order to fully understand their potential therapeutic value.

Higher dietary protein intake is associated with sarcopenia in older British twins.

BACKGROUND: Sarcopenia, characterised by an accelerated loss of skeletal muscle mass and function, is associated with negative outcomes. This study aimed to evaluate factors associated with skeletal muscle strength, mass and sarcopenia, particularly protein intake, and to assess whether shared twin characteristics are important. METHODS: This study utilised cross-sectional data from a study of community-dwelling twins aged ≥60 years. Multivariable logistic regression and between- and within-twin pair regression modelling were used. RESULTS: Participants (n = 3,302) were 89% female (n = 2,923), aged a mean of 72.1 (±7.3) years and composed of 858 (55%) monozygotic, 709 (45%) dizygotic twin pairs and 168 individual lone twins. Using optimal protein intake as the reference group (1.0-1.3 g/kg/day), there was no significant association between protein intake (neither high nor low) and low muscle strength, or between low protein intake and sarcopenia (odds ratio (OR) 0.7; 95% confidence interval (CI) 0.39-1.25; P = 0.229) in unadjusted models. High protein intake (>1.3 g/kg/day) was associated with low muscle mass (OR 1.76; 95% CI 1.39-2.24; P < 0.0001), while low protein intake was protective (OR 0.52; 95% CI 0.40-0.67; P < 0.0001). High protein intake was associated with sarcopenia (OR 2.04; 95% CI 1.21-3.44; P = 0.008), and this was robust to adjustment for demographic, anthropometric and dietary factors. The association between muscle strength and weight, body mass index, healthy eating index, protein intake and alpha diversity was not significantly influenced by shared twin factors, indicating greater amenability to interventions. CONCLUSIONS: High protein intake is associated with sarcopenia in a cohort of healthy older twins.

Emulsifiers in ultra-processed foods in the UK food supply.

OBJECTIVE: Ultra-processed foods (UPF), including those containing food additive emulsifiers, have received research attention due to evidence implicating them in the pathogenesis of certain diseases. The aims of this research were to develop a large-scale, brand-level database of UPF in the UK food supply and to characterise the occurrence and co-occurrence of food additive emulsifiers. DESIGN: A database was compiled sampling all products from the food categories contributing to energy intake from UPF in the UK from the National Diet and Nutrition Survey (2008-2014). Every food in these categories were identified from online supermarket provision from the 'big four' supermarkets that dominate the market share in the UK, comprising Tesco, Sainsbury's, Asda and Morrisons. SETTING: Major supermarkets in the UK. RESULTS: A total of 32 719 food products in the UK supermarket food supply were returned in searches. Of these, 12 844 products were eligible and manually reviewed for the presence of emulsifiers. Emulsifiers were present in 6642 (51·7 %) food products. Emulsifiers were contained in 95·0 % of 'Pastries, buns and cakes', 81·9 % of 'Milk-based drinks', 81·0 % of 'Industrial desserts' and 77·5 % of 'Confectionary'. Fifty-one per cent of all emulsifier-containing foods contained multiple emulsifiers. Across emulsifier-containing foods, there were a median of two emulsifiers (IQR 2) per product. The five most common emulsifiers were lecithin (23·4 % of all products), mono- and diglycerides of fatty acids (14·5 %), diphosphates (11·6 %), and xanthan gum and pectin (8·0 %). CONCLUSIONS: Findings from this study are the first to demonstrate the widespread occurrence and co-occurrence of emulsifiers in UPF in the UK food supply.

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.

Behavioral and Diet Therapies in Integrated Care for Patients With Irritable Bowel Syndrome.

Irritable bowel syndrome (IBS) is a common, symptom-based condition that has negative effects on quality of life and costs health care systems billions of dollars each year. Until recently, management of IBS has focused on over-the-counter and prescription medications that reduce symptoms in fewer than one-half of patients. Patients have increasingly sought natural solutions for their IBS symptoms. However, behavioral techniques and dietary modifications can be effective in treatment of IBS. Behavioral interventions include gastrointestinal-focused cognitive behavioral therapy and gut-directed hypnotherapy to modify interactions between the gut and the brain. In this pathway, benign sensations from the gut induce maladaptive cognitive or affective processes that amplify symptom perception. Symptoms occur in response to cognitive and affective factors that trigger fear of symptoms or lack of acceptance of disease, or from stressors in the external environment. Among the many dietary interventions used to treat patients with IBS, a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols is the most commonly recommended by health care providers and has the most evidence for efficacy. Patient with IBS who choose to follow a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols should be aware of its 3 phases: restriction, reintroduction, and personalization. Management of IBS should include an integrated care model in which behavioral interventions, dietary modification, and medications are considered as equal partners. This approach offers the greatest likelihood for success in management of patients with IBS.

Optimal Design of Clinical Trials of Dietary Interventions in Disorders of Gut-Brain Interaction.

There is accumulating evidence for the fundamental role of diet in the integrated care of disorders of gut-brain interaction. Food is a complex mixture of components with individual, synergistic, and antagonistic effects, compared with the relative purity of a pharmaceutical. Food is also an inherent part of individuals' daily lives, and food choice is strongly tied to food preferences, personal beliefs, cultural and religious practices, and economic status, which can influence its ability to function as a therapeutic intervention. Hence, randomized controlled trials of dietary interventions carry unique methodological complexities that are not applicable to pharmaceutical trials that if disregarded can pose significant risk to trial quality. The challenges of designing and delivering the dietary intervention depend on the type of intervention (i.e., nutrient vs food supplementation or whole-diet intervention). Furthermore, there are multiple modes of delivery of dietary interventions, each with their own advantages (e.g., the high precision of feeding trials and the strong clinical applicability of dietary counseling trials). Randomized placebo-controlled trials of dietary interventions are possible with sufficient attention to their design and methodological nuances. Collaboration with experts in nutrition and dietetics is essential for the planning phase; however, even with expert input, not all challenges can be overcome. Researchers undertaking future dietary trials must be transparent in reporting these challenges and approaches for overcoming them. This review aims to provide guiding principles and recommendations for addressing these challenges to facilitate the conduct and reporting of high-quality trials that inform and improve clinical practice.

Low FODMAP diet in irritable bowel syndrome: a review of recent clinical trials and meta-analyses.

PURPOSE OF REVIEW: The low fermentable oligosaccharides, disaccharides, monosaccharides and polyol (FODMAP) diet is widely used in the dietary management of irritable bowel syndrome (IBS). The aim of this review is to summarize recent evidence regarding the use of the low FODMAP diet in IBS and other gastrointestinal disorders from recent clinical trials and meta-analyses. RECENT FINDINGS: Several recent systematic reviews and meta-analyses support the use of low FODMAP restriction for global symptoms in IBS in the short term. Uncontrolled follow-up studies show that at least 50% of individuals experience symptom relief following restriction, reintroduction and personalization in the long term. Although evidence from comparative trials in IBS suggests potential benefit of less burdensome approaches (e.g. standard IBS diet and low lactose diet) many studies are insufficiently powered. One established mechanism is colonic gas production that may induce pain signalling measurable in the brain, however altered gastrointestinal epithelial integrity and shifts in microbiome composition and function may also be involved. SUMMARY: Quality trials of the low FODMAP diet are emerging and have been transformational in supporting the widespread application to IBS management in some areas (e.g. short-term effectiveness), whereas other areas still require considerable improvements in research evidence (e.g. long-term effectiveness, mechanisms and educational delivery).

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.

Food-related quality of life in inflammatory bowel disease: measuring the validity and reliability of the Turkish version of FR-QOL-29.

PURPOSE: Food-related quality of life is considerably impaired in patients with inflammatory bowel disease (IBD) and should be widely measured in research and clinical practice. This study aims to translate the FR-QoL-29 instrument to the Turkish language and evaluate its validity and reliability in Turkish patients with IBD. METHODS: The FR-QoL-29 was forwards and backwards translated into Turkish and the validity and reliability of the FR-QoL-29-Turkish measured at two tertiary hospitals in Ankara, Turkey. Participants completed four questionnaires regarding: sociodemographic; clinical (disease type and activity), and nutritional characteristics (MUST) together with FR-QoL-29-Turkish. In addition, 30 patients repeated the questionnaires after two weeks. collected. Pearson correlation coefficients and Cronbach α were used to assess reliability and validity (p < 0.05). RESULTS: A total of 180 participants with IBD (78 Crohn's disease, 102 ulcerative colitis), with a mean age of 45.9 ± 12.5 years, were included. Bartlett's sphericity test was statistically significant (p < 0.001), meeting the prerequisite for factor analysis, and the adequacy of the sample size for factor analysis was confirmed by a high Kaiser-Meyer-Olkin (KMO = 0.92). Validity was confirmed by factor loadings ranging from 0.310 to 0.858. Item-total score correlations ranged from 0.258 to 0.837 and Cronbach's α coefficient was 0.96 for the whole questionnaire indicating high internal consistency. CONCLUSIONS: FR-QoL-29-Turkish is a valid and reliable measure of food-related quality of life in IBD patients with Turkish language. The FR-QoL-29-Turkish gives a comprehensive overview of the main aspects of food quality of life and can be used as a useful tool in both research and clinical practice.

Fermented foods: Availability, cost, ingredients, nutritional content and on-pack claims.

INTRODUCTION: Fermented foods have been consumed for millennia and commercially-produced variants are now available in the food supply. The present study aimed to investigate the availability, cost, ingredients, nutritional content and on-pack claims of commercially-available fermented foods in the UK. METHODS: All products from seven categories of commercially-available fermented foods were systematically identified at eight national supermarket chains in the UK. Data were extracted from manufacturer and retailer websites and were compared between categories using a Kruskal-Wallis test and Fisher's exact test. RESULTS: In total, 143 fermented foods were identified, with kombucha (41, 28.7%), kefir drinks (32, 22.4%), sauerkraut (22, 15.4%) and kefir yoghurts (21, 14.7%) being most common. The number of products sold at each retailer differed between categories (p = 0.016), and was greatest for kefir drink (median = 7.0, interquartile range [IQR] = 9.0), kombucha (median = 5.5, IQR = 11.5) and kefir yoghurts (median = 5.0, IQR = 8.5). Kombucha (£1.99 per serving) and kefir drinks (£1.26 per serving) were the most expensive fermented foods and sauerkraut (£0.66 per serving) and miso (£0.20 per serving) were the least expensive. Energy, fat, saturated fat, sugar, protein and salt content varied between fermented foods (p < 0.001). Nutrition claims were made on 72 (50.3%) products, the total number of cultures was labelled on 29 (20.3%), specific strains were named on 53 (37.1%) and bacteria-related benefits were promoted on 39 (27.3%) products. CONCLUSIONS: Commercially-produced fermented foods are widely available in the UK but are diverse in their cost, nutritional content, ingredients and use of on-pack claims. Consumers should be aware of these variations given the limited evidence of functional benefits from controlled human trials.

Knowledge, perceptions and behaviours regarding dietary management of adults living with phenylketonuria.

BACKGROUND: Lifelong dietary treatment remains the mainstay for many with phenylketonuria (PKU); however, adherence is known to reduce with age. It remains unclear whether knowledge and perceptions of the PKU diet amongst adults with PKU influence dietary behaviours. METHODS: A nationwide questionnaire survey was performed to investigate the knowledge and perceptions, and associated diet behaviours of adults with PKU in the UK. The survey was sent to adults with PKU under the care of the host hospital and members of the National Society of PKU. RESULTS: One hundred and thirty-seven respondents (n = 78 females, 56.9%) completed the survey with a mean age of 34 years and 4 months (16-65 years). Sixty (43.8%) respondents had always followed a PKU diet, 39 (28.5%) returned to diet and 35 (25.5%) were off diet. Overall mean ± SD knowledge score was 75.2% ± 13.4%, with significantly higher scores for knowledge of PKU (80.7% ± 16.2%) compared to knowledge specifically of the PKU diet (72.6% ± 14.5%, p < 0.001). Knowledge was associated with dietary adherence. Respondents who always followed a PKU diet had similar knowledge to those who returned to diet, whereas respondents off diet had significantly lower scores. Perception of the diet was not a predictor of dietary adherence, with the exception of whether patients had concerns for their long-term health when on diet or felt well when not following a diet. CONCLUSIONS: The present study highlights the importance of ongoing dietetic input in building knowledge and skills for dietary management. Further research is needed to understand the motivators and beliefs that influence dietary adherence.

Fat-soluble vitamin assessment, deficiency and supplementation in infants with cholestasis.

BACKGROUND: Infants with cholestasis are at risk of fat-soluble vitamin deficiency. The present study amied to review practice relating to the assessment, deficiency and supplementation of fat-soluble vitamins in infants with cholestasis. METHODS: The medical records of all newly diagnosed infants with cholestasis (conjugated bilirubin >17 mmol L-1 />20% total bilirubin) at King's College Hospital between 2017 and 2019 were reviewed. Data extracted included bilirubin, serum vitamin concentrations (A, D, E), international normalised ratio and evidence of supplementation at initial assessment, as well as at 3 and 6 months. Rates of vitamin assessment, deficiency and supplementation were compared using chi-squared or Fisher's exact test. RESULTS: In total, 136 infants (87 male) with idiopathic neonatal cholestasis (n = 62), biliary atresia (n = 40) and other aetiology (n = 34) were included. Assessment of serum vitamins (A, D, E) was low (33.3%-52.2%) and deficiency was initially high for vitamin D (60.6%) and vitamin E (70.9%). Supplementation prevalence at initial assessment was high (A, E, K), but dropped significantly at 3 and 6 months for vitamin E (p = 0.003) and vitamin K (p = 0.001), whereas vitamin D supplementation was consistently low throughout (25%-33.3%). Infants with biliary atresia were more likely to have vitamins assessed (3 months), be deficient initially (D, E) and supplemented (E, K) throughout. Supplementation continued in up to 80% of infants despite cholestasis resolving. CONCLUSIONS: Supplementation was generally high and continued in many despite cholestasis resolving. Deficiency of vitamin D and vitamin E was high at initial assessment, although lower at follow-up. Actual prevalence of deficiency of all vitamins is unknown because monitoring was not consistently performed.

Undertaking a research project improves confidence in research skills among student dietitians.

BACKGROUND: Research is a cornerstone of evidence-based dietetic practice. Research skills are often taught at university through experiential learning during a final-year research project. The present study aimed to investigate attitudes towards research and confidence in research skills among student dietitians before and after a research project. METHODS: A questionnaire survey of student dietitians' attitudes to research and confidence in research skills was undertaken before and after completing a research project at two universities in London, UK. Dichotomous data were compared before and after the research project using a McNemar's test. Factors associated with 'high confidence' or 'improved confidence' in overall research skills at the end of the research project were investigated using multivariable logistic regression. RESULTS: In total, 160 student dietitians completed a questionnaire before and after their research project. The majority had positive attitudes to research both before and after their research project. There was an increase in numbers with 'high confidence' in overall research skills before (13; 8.1%) and after (79; 49.4%) the research project (p < 0.001), and 113 (70.6%) reported 'improved confidence' in overall research skills. The only factor associated with 'high confidence' in overall research skills was having 'high levels of involvement in the overall research process' (odds ratio = 6.13, 95% confidence interval = 2.03-18.49, p = 0.001). CONCLUSIONS: Student dietitians have positive attitudes towards research and undertaking a research project significantly improves confidence in their research skills. A higher level of involvement in the research project is the single most significant factor associated with high confidence in research skills.

Effects of Low FODMAP Diet on Symptoms, Fecal Microbiome, and Markers of Inflammation in Patients With Quiescent Inflammatory Bowel Disease in a Randomized Trial.

BACKGROUND & AIMS: There is limited evidence that a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) reduces gut symptoms in quiescent inflammatory bowel disease (IBD). We performed a randomized, controlled trial to investigate the effects of a low FODMAP diet on persistent gut symptoms, the intestinal microbiome, and circulating markers of inflammation in patients with quiescent IBD. METHODS: We performed a single-blind trial of 52 patients with quiescent Crohn's disease or ulcerative colitis and persistent gut symptoms at 2 large gastroenterology clinics in the United Kingdom. Patients were randomly assigned to groups that followed a diet low in FODMAPs (n = 27) or a control diet (n = 25), with dietary advice, for 4 weeks. Gut symptoms and health-related quality of life were measured using validated questionnaires. Stool and blood samples were collected at baseline and end of trial. We assessed fecal microbiome composition and function using shotgun metagenomic sequencing and phenotypes of T cells in blood using flow cytometry. RESULTS: A higher proportion of patients reported adequate relief of gut symptoms following the low FODMAP diet (14/27, 52%) than the control diet (4/25, 16%, P=.007). Patients had a greater reduction in irritable bowel syndrome severity scores following the low FODMAP diet (mean reduction of 67; standard error, 78) than the control diet (mean reduction of 34; standard error, 50), although this difference was not statistically significant (P = .075). Following the low FODMAP diet, patients had higher health-related quality of life scores (81.9 ± 1.2) than patients on the control diet (78.3 ± 1.2, P = .042). A targeted analysis revealed that in stool samples collected at the end of the study period, patients on the low FODMAP diet had significantly lower abundance of Bifidobacterium adolescentis, Bifidobacterium longum, and Faecalibacterium prausnitzii than patients on control diet. However, microbiome diversity and markers of inflammation did not differ significantly between groups. CONCLUSIONS: In a trial of the low FODMAP diet vs a control diet in patients with quiescent IBD, we found no significant difference after 4 weeks in change in irritable bowel syndrome severity scores, but significant improvements in specific symptom scores and numbers reporting adequate symptom relief. The low FODMAP diet reduced fecal abundance of microbes believed to regulate the immune response, compared with the control diet, but had no significant effect on markers of inflammation. We conclude that a 4-week diet low in FODMAPs is safe and effective for managing persistent gut symptoms in patients with quiescent IBD. www.isrctn.com no.: ISRCTN17061468.

Relationship Between Skeletal Muscle Area and Density and Clinical Outcome in Adults Receiving Venovenous Extracorporeal Membrane Oxygenation.

OBJECTIVES: To investigate the prevalence of low skeletal muscle index (area normalized for height) and density, their trajectory of change, and to determine associations with clinical outcome in adults with severe respiratory failure requiring venovenous extracorporeal membrane oxygenation. DESIGN: Prospective observational study. PATIENTS: Adults receiving venovenous extracorporeal membrane oxygenation for a minimum of 72 hours and a maximum of 6 months between September 2010 and June 2017, who had a CT scan which included the third lumbar vertebra. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Skeletal muscle index and density was determined using Slice-O-Matic V5.0 (TomoVision, Montreal, QC, Canada). Low skeletal muscle index and density were defined using published criteria. Regression models were used to assess for associations between muscle index and density and clinical outcome. Two-hundred fifteen patients, median (interquartile range) age 46 years (35.0-57.0 yr) were included. Forty-five patients (21.1%) had low skeletal muscle index, and 48 (22.3%) had low skeletal muscle density on commencement of venovenous extracorporeal membrane oxygenation. Low skeletal muscle index was more prevalent in males (28.8% vs 11.6%; χ2 = 9.4; p = 0.002) and was associated with a longer duration of venovenous extracorporeal membrane oxygenation (B = 5.0; 95% CI, 0.2-9.9; p = 0.042). Higher skeletal muscle density was independently associated with ICU survival (odds ratio 1.6 per 10 Hounsfield units; 95% CI, 1.1-2.5; p = 0.025). No relationship was observed between skeletal muscle index nor density and physical function. Adequacy of energy and protein did not influence change in skeletal muscle index or density. CONCLUSIONS: Low skeletal muscle index at the commencement of venovenous extracorporeal membrane oxygenation was associated with a longer duration of venovenous extracorporeal membrane oxygenation, whereas preserved skeletal muscle density was associated with improved survival.

Novel (R)-6,6a,7,8,9,10-hexahydro-5H-pyrazino[1,2-a][1,n]naphthyridines as potent and selective agonists of the 5-HT2C receptor.

A series of novel (R)-6,6a,7,8,9,10-hexahydro-5H-pyrazino[1,2-a][1,n]naphthyridines were identified as potent and selective agonists of the 5-HT2C receptor. Optimizations performed on a previously reported series of racemic tetrahydroquinoline-based tricyclic amines, delivered an advanced drug lead, (R)-4-(3,3,3-trifluoropropyl)-6,6a,7,8,9,10-hexahydro-5H-pyrazino[1,2-a][1,8]naphthyridine, which displayed excellent in vitro and in vivo pharmacological profiles.

The PROMOTe study: targeting the gut microbiome with prebiotics to overcome age-related anabolic resistance: protocol for a double-blinded, randomised, placebo-controlled trial.

BACKGROUND: Loss of skeletal muscle mass and strength occurs with increasing age and is associated with loss of function, disability, and the development of sarcopenia and frailty. Dietary protein is essential for skeletal muscle function, but older adults do not anabolise muscle in response to protein supplementation as well as younger people, so called 'anabolic resistance'. The aetiology and molecular mechanisms for this are not understood, however the gut microbiome is known to play a key role in several of the proposed mechanisms. Thus, we hypothesise that the gut microbiome may mediate anabolic resistance and therefore represent an exciting new target for ameliorating muscle loss in older adults. This study aims to test whether modulation of the gut microbiome using a prebiotic, in addition to protein supplementation, can improve muscle strength (as measured by chair-rise time) versus protein supplementation alone. METHODS: The study is a randomised, double-blinded, placebo-controlled trial, with two parallel arms; one will receive prebiotic and protein supplementation, and the other will receive placebo (maltodextrin) and protein supplementation. Participants will be randomised as twin pairs, with one twin from each pair in each arm. Participants will be asked to take supplementation once daily for 12 weeks in addition to resistance exercises. Every participant will receive a postal box, containing their supplements, and the necessary equipment to return faecal, urine, saliva and capillary blood samples, via post. A virtual visit will be performed using online platform at the beginning and end of the study, with measures taken over video. Questionnaires, food diary and cognitive testing will be sent out via email at the beginning and end of the study. DISCUSSION: This study aims to provide evidence for the role of the gut microbiome in anabolic resistance to dietary protein. If those who take the prebiotic and protein supplementation have a greater improvement in muscle strength compared with those who take protein supplementation alone, this would suggest that strategies to modify the gut microbiome may reduce anabolic resistance, and therefore potentially mitigate sarcopenia and frailty in older adults. TRIAL REGISTRATION: Clinicaltrials.gov: NCT04309292 . Registered on the 2nd May 2020.

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.