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Abstract Background and aims Waist circumference (WC) is a significant indicator of body adiposity and is associated with increased mortality and morbidity of cardiovascular diseases. Although, single nutrient intake and candidate genes were previously associated with WC. Little is known about WC association with overall diet quality, genetic risk score and gene-nutrient interaction. This study aims to investigate the influence of overall diet quality and multiple WC-associated single nucleotide polymorphisms on WC. In addition to investigating gene-nutrient interaction association with WC. Methods This study explored cross-sectional data from two large sample-size studies, to provide reproducible results. As a representation of the UK population, the Airwave Health Monitoring Study (n = 6,502) and the UK-Biobank Cohort Study (n = 171,129) were explored for factors associated with WC. Diet quality was evaluated based on the Mellen Index for Dietary Approaches to Stop Hypertension (Mellen-DASH). The genetic risk score for WC (GRS-Waist) was calculated by screening the population genotype for WC-associated single nucleotide polymorphisms. Multivariate linear regression models were built to explore WC association with diet quality and genetic risk score. Gene-nutrient interaction was explored by introducing the interaction term (GRS-Waist X Mellen-DASH score) to multivariate linear regression analysis. Results The prevalence of high WC (Female > 80 cm, Male > 94 cm) was 46.5% and 51.7% in both populations. Diet quality and genetic risk score of WC were significantly associated with WC. There was no evidence of interaction between GRS-Waist, DASH diet scores and nutrient intake on WC. Conclusion This study’s findings provided reproducible results on waist circumference association with diet and genetics and tested the possibility of gene-nutrient interaction. These reproducible results are successful in building the foundation for using diet and genetics for early identification of those at risk of having high WC and WC-associated diseases. In addition, evidence on gene-diet interactions on WC is limited and lacks replication, therefore our findings may guide future research in investigating this interaction and investigating its application in precision nutrition.

BackgroundShared plate eating (SPE), defined as two or more individuals eating directly from the same plate or bowl, is a common household food consumption practice in many Low- and Middle-Income Countries (LMICs). Examination of household engagement in SPE remains largely unexplored, highlighting a gap in research when interpreting dietary information obtained from these settings. The dearth of research into SPE can be attributed to the inherent limitations of traditional dietary assessment methods which constrain their usability in settings where SPE is common.ObjectiveIn this expository narrative, we describe what SPE is when it is practiced in an LMIC such as Ghana; and also compare the frequency of SPE versus individual plate eating (IPE) by different household members in rural and urban households using a wearable camera (Automatic Ingestion Monitor version 2: AIM-2).MethodsPurposive convenience sampling was employed to recruit and enroll 30 households each from an urban and a rural community (n = 60 households) in Ghana. The AIM-2 was worn on eyeglass frames for 3 days by selected household members. The AIM-2, when worn, automatically collects images to capture food consumption in participants’ environments, thus enabling passive capture of household SPE dynamics.ResultsA higher percentage of SPE occasions was observed for rural (96.7%) compared to urban (36.7%) households (p

Meat-based foods have significant environmental impacts that are lower for plant-based meat alternatives. Fungi-based mycoprotein offers another alternative to meat, but its comparative environmental impacts have not been comprehensively reviewed. We identified life cycle assessments (LCAs) of mycoprotein-based meat alternatives using ProQuest, Scopus and Web of Science, and the grey literature. Studies were included if they were published in the English language from 1 January 2013 until 18 September 2023, reported process-based LCAs with functional units by product weight, and reported any environmental impact measure, system boundary, or region. Data for mycoprotein was compared against plant-based meat alternatives for base-protein, burgers, mince and sausages, and against meats. Five LCAs of mycoprotein-based products were identified. Greenhouse gas emissions (GHGe) were lower for mycoprotein (0.73 kgCO2eq/kg) compared to soy (1.21 kgCO2eq/kg) or pea protein concentrate (1.91 kgCO2eq/kg). GHGe for mycoprotein-based product types were lower than or comparable to equivalent plant-based products, and lower compared to meat. GHGe from the ingredient production stage were generally lower for mycoprotein-based products compared to plant-based products. Further data are needed to compare land use and water scarcity impacts. Mycoprotein offers clear environmental advantages over meat, but distinctions between mycoprotein and plant-based alternatives require more comprehensive data.

The evidence on the impact of fruits and vegetable types on cardiovascular risk factors remains limited. Specifically, the utilisation of biomarkers to objectively measure dietary compliance and metabolic responses is emerging. This protocol and baseline characteristics of a pilot randomised controlled, crossover, dietary intervention study aimed to examine the effects of citrus fruits, cruciferous vegetables, or common fruits and vegetables on cardiovascular risk factors. A total of 39 volunteers with untreated prehypertension was recruited and consumed a standardised, provided diet with eight daily portions of citrus fruits and cruciferous vegetables, common fruits and vegetables, or a low fruit and vegetable diet (two portions/d, control diet) in a random order for 2 weeks each, separated by a wash-out week. A targeted cohort-based recruitment strategy was utilised and resulted in 74% of participants recruited by re-contacting preselected individuals from two cohort studies with a 15% average enrolment rate. Participants had an average age of 54.4 years (±6.1 years), BMI of 27.9 kg/m2, and BP of 135/81 mmHg and were mainly male (67%). The primary outcome was office blood pressure; secondary outcomes included arterial stiffness, lipid profiles, inflammation, cognitive function, and subjective mood. Biofluids, i.e., 24 h urine, stool, and blood samples, were collected for biomarker measurements with multiple metabolomic platforms and the gut microbial composition, together with traditional dietary biomarkers.

Summary: The manifestation of metabolic deteriorations that accompany overweight and obesity can differ greatly between individuals, giving rise to a highly heterogeneous population. This inter-individual variation can impede both the provision and assessment of nutritional interventions as multiple aspects of metabolic health should be considered at once. Here, we apply the Mixed Meal Model, a physiology-based computational model, to characterize an individual’s metabolic health in silico. A population of 342 personalized models were generated using data for individuals with overweight and obesity from three independent intervention studies, demonstrating a strong relationship between the model-derived metric of insulin resistance (ρ = 0.67, p

Abstract We evaluate the shared genetic regulation of mRNA molecules, proteins and metabolites derived from whole blood from 3029 human donors. We find abundant allelic heterogeneity, where multiple variants regulate a particular molecular phenotype, and pleiotropy, where a single variant associates with multiple molecular phenotypes over multiple genomic regions. The highest proportion of share genetic regulation is detected between gene expression and proteins (66.6%), with a further median shared genetic associations across 49 different tissues of 78.3% and 62.4% between plasma proteins and gene expression. We represent the genetic and molecular associations in networks including 2828 known GWAS variants, showing that GWAS variants are more often connected to gene expression in trans than other molecular phenotypes in the network. Our work provides a roadmap to understanding molecular networks and deriving the underlying mechanism of action of GWAS variants using different molecular phenotypes in an accessible tissue.

RationaleEvidence suggests consumption of a Mediterranean diet (MD) can positively impact both maternal and offspring health, potentially mediated by a beneficial effect on inflammatory pathways. We aimed to apply metabolic profiling of serum and urine samples to assess differences between women who were stratified into high and low alignment to a MD throughout pregnancy and investigate the relationship of the diet to inflammatory markers.MethodsFrom the ORIGINS cohort, 51 pregnant women were stratified for persistent high and low alignment to a MD, based on validated MD questionnaires. 1H Nuclear Magnetic Resonance (NMR) spectroscopy was used to investigate the urine and serum metabolite profiles of these women at 36 weeks of pregnancy. The relationship between diet, metabolite profile and inflammatory status was investigated.ResultsThere were clear differences in both the food choice and metabolic profiles of women who self-reported concordance to a high (HMDA) and low (LMDA) Mediterranean diet, indicating that alignment with the MD was associated with a specific metabolic phenotype during pregnancy. Reduced meat intake and higher vegetable intake in the HMDA group was supported by increased levels of urinary hippurate (p = 0.044) and lower creatine (p = 0.047) levels. Serum concentrations of the NMR spectroscopic inflammatory biomarkers GlycA (p = 0.020) and GlycB (p = 0.016) were significantly lower in the HDMA group and were negatively associated with serum acetate, histidine and isoleucine (p

Penney et al. conduct microbial and metabolic profiling in people with obesity, with or without type 2 diabetes, undergoing two types of bariatric surgery. Integrative analysis identifies multi-omic signatures associated with response to surgery, body mass index, and glycaemic control.

IntroductionDietary assessment is important for understanding nutritional status. Traditional methods of monitoring food intake through self-report such as diet diaries, 24-hour dietary recall, and food frequency questionnaires may be subject to errors and can be time-consuming for the user.MethodsThis paper presents a semi-automatic dietary assessment tool we developed - a desktop application called Image to Nutrients (I2N) - to process sensor-detected eating events and images captured during these eating events by a wearable sensor. I2N has the capacity to offer multiple food and nutrient databases (e.g., USDA-SR, FNDDS, USDA Global Branded Food Products Database) for annotating eating episodes and food items. I2N estimates energy intake, nutritional content, and the amount consumed. The components of I2N are three-fold: 1) sensor-guided image review, 2) annotation of food images for nutritional analysis, and 3) access to multiple food databases. Two studies were used to evaluate the feasibility and usefulness of I2N: 1) a US-based study with 30 participants and a total of 60 days of data and 2) a Ghana-based study with 41 participants and a total of 41 days of data).ResultsIn both studies, a total of 314 eating episodes were annotated using at least three food databases. Using I2N’s sensor-guided image review, the number of images that needed to be reviewed was reduced by 93% and 85% for the two studies, respectively, compared to reviewing all the images.DiscussionI2N is a unique tool that allows for simultaneous viewing of food images, sensor-guided image review, and access to multiple databases in one tool, making nutritional analysis of food images efficient. The tool is flexible, allowing for nutritional analysis of images if sensor signals aren’t available.

BackgroundType 2 diabetes (T2D) diagnoses are predicted to reach 643 million by 2030, increasing incidences of cardiovascular disease and other comorbidities. Rapidly digestible starch elevates postprandial glycemia and impinges glycemic homeostasis, elevating the risk of developing T2D. Starch can escape digestion by endogenous enzymes in the small intestine when protected by intact plant cell walls (resistant starch type 1), when there is a high concentration of amylose (resistant starch type 2) and when the molecule undergoes retrogradation (resistant starch type 3) or chemical modification (resistant starch type 4). Dietary interventions using resistant starch may improve glucose metabolism and insulin sensitivity. However, few studies have explored the differential effects of resistant starch type. This systematic review and meta-analysis aims to compare the effects of the resistant starch from intact plant cell structures (resistant starch type 1) and resistant starch from modified starch molecules (resistant starch types 2–5) on fasting and postprandial glycemia in subjects with T2D and prediabetes.MethodsDatabases (PubMed, SCOPUS, Ovid MEDLINE, Cochrane, and Web of Science) were systematically searched for randomized controlled trials. Standard mean difference (SMD) with 95% confidence intervals (CI) were determined using random-effects models. Sub-group analyses were conducted between subjects with T2D versus prediabetes and types of resistant starch.ResultsThe search identified 36 randomized controlled trials (n = 982), 31 of which could be included in the meta-analysis. Resistant starch type 1 and type 2 lowered acute postprandial blood glucose [SMD (95% CI) = -0.54 (–1.0, –0.07)] and [–0.96 (–1.61, –0.31)]. Resistant starch type 2 improved acute postprandial insulin response [–0.71 (–1.31, –0.11)]. In chronic studies, resistant starch type 1 and 2 lowered postprandial glucose [–0.38 (–0.73, –0.02), –0.29 (–0.53, –0.04), respectively] and resistant starch type 2 intake improved fasting glucose [–0.39 (–0.66, –0.13)] and insulin [–0.40 (–0.60, –0.21)].ConclusionResistant starch types 1 and 2 may influence glucose homeostasis via discrete mechanisms, as they appear to influence glycemia differently. Further research into resistant starch types 3, 4, and 5 is required to elucidate their effect on glucose metabolism. The addition of resistant starch as a dietary intervention for those with T2D or prediabetes may prevent further deterioration of glycemic control.

Background: Accurate estimation of dietary intake is challenging. However, whilst some progress has been made in high-income countries, low- and middle-income countries (LMICs) remain behind, contributing to critical nutritional data gaps. This study aimed to validate an objective, passive image-based dietary intake assessment method against weighed food records in London, UK, for onward deployment to LMICs. Methods: Wearable camera devices were used to capture food intake on eating occasions in 18 adults and 17 children of Ghanaian and Kenyan origin living in London. Participants were provided pre-weighed meals of Ghanaian and Kenyan cuisine and camera devices to automatically capture images of the eating occasions. Food images were assessed for portion size, energy, nutrient intake, and the relative validity of the method compared to the weighed food records. Results: The Pearson and Intraclass correlation coefficients of estimates of intakes of food, energy, and 19 nutrients ranged from 0.60 to 0.95 and 0.67 to 0.90, respectively. Bland–Altman analysis showed good agreement between the image-based method and the weighed food record. Under-estimation of dietary intake by the image-based method ranged from 4 to 23%. Conclusions: Passive food image capture and analysis provides an objective assessment of dietary intake comparable to weighed food records.

Background: Outcomes in children hospitalised with severe acute malnutrition (SAM) remain poor. The current milk-based formulations focus on restoring weight-gain but fail to address modification of the integrity of the gut barrier and may exacerbate malabsorption owing to functional lactase, maltase and sucrase deficiency. We hypothesise that nutritional feeds should be designed to promote bacterial diversity and restore gastrointestinal (GI) barrier function. Methods: Our major objective was to develop a lactose-free, fermentable carbohydrate-containing alternative to traditional F75 and F100 formulae for the inpatient treatment of SAM. New target nutritional characteristics were developed and relevant food and infant food specific legislation were reviewed. Suitable certified suppliers of ingredients were identified. Processing and manufacture steps were evaluated and optimised for safety (nutritional, chemical and microbiological), and efficacy at meeting target characteristics (lactose-free, containing resistant starch 0.4-0.5% final product weight). Results: A final validated production process was developed and implemented to produce a novel food product for the inpatient treatment of SAM in children in Africa designed to reduce risk of osmotic diarrhoea and support symbiotic gut microbial populations. The final product matched the macronutrient profile of double-concentrated F100, adhered to all relevant legislation regulating infant foods, was lactose free, and contained 0.6% resistant starch. Chickpeas were selected as the source of resistant starch, since they are widely grown and eaten throughout Africa. Micronutrient content could not be matched in this ready-to-use product, so this was replaced at the point of feeding, as was fluid lost through concentration. Conclusions: The processes and product described illustrate the development steps for a novel nutritional product. The new feed product was ready for evaluation for safety and efficacy in a phase II clinical trial in Ugandan children admitted to hospital with SAM (Modifying Intestinal MicroBiome with Legume-Based feed 2: MIMBLE feed 2 (ISRCTN10309022)).

Our gastrointestinal system functions to digest and absorb ingested food, but it is also home to trillions of microbes that change across time, nutrition, lifestyle, and disease conditions. Largely commensals, these microbes are gaining prominence with regards to how they collectively affect the function of important metabolic organs, from the adipose tissues to the endocrine pancreas to the skeletal muscle. Muscle, as the biggest utilizer of ingested glucose and an important reservoir of body proteins, is intricately linked with homeostasis, and with important anabolic and catabolic functions, respectively. Herein, we provide a brief overview of how gut microbiota may influence muscle health and how various microbes may in turn be altered during certain muscle disease states. Specifically, we discuss recent experimental and clinical evidence in support for a role of gut-muscle crosstalk and include suggested underpinning molecular mechanisms that facilitate this crosstalk in health and diseased conditions. We end with a brief perspective on how exercise and pharmacological interventions may interface with the gut-muscle axis to improve muscle mass and function.

Abstract Background Skeletal muscle mass begins to decline from 40 years of age. Limited data suggest that dietary fibre may modify lean body mass (BM), of which skeletal muscle is the largest and most malleable component. We investigated the relationship between dietary fibre intake, skeletal muscle mass and associated metabolic and functional parameters in adults aged 40 years and older. Methods We analysed cross‐sectional data from the US National Health and Nutrition Examination Survey between 2011 and 2018 from adults aged 40 years and older. Covariate‐adjusted multiple linear regression analyses were used to evaluate the association between dietary fibre intake and BM components (BM, body mass index [BMI], total lean mass, appendicular lean mass, bone mineral content, total fat, trunk fat; n = 6454), glucose homeostasis (fasting glucose, fasting insulin, HOMA2‐IR; n = 5032) and skeletal muscle strength (combined grip strength; n = 5326). BM components and skeletal muscle strength were expressed relative to BM (per kg of BM). Results Higher intakes of dietary fibre were significantly associated with increased relative total lean mass (β: 0.69 g/kg BM; 95% CI, 0.48–0.89 g/kg BM; P

Summary: Despite the pivotal role played by elevated circulating triglyceride levels in the pathophysiology of cardio-metabolic diseases many of the indices used to quantify metabolic health focus on deviations in glucose and insulin alone. We present the Mixed Meal Model, a computational model describing the systemic interplay between triglycerides, free fatty acids, glucose, and insulin. We show that the Mixed Meal Model can capture deviations in the post-meal excursions of plasma glucose, insulin, and triglyceride that are indicative of features of metabolic resilience; quantifying insulin resistance and liver fat; validated by comparison to gold-standard measures. We also demonstrate that the Mixed Meal Model is generalizable, applying it to meals with diverse macro-nutrient compositions. In this way, by coupling triglycerides to the glucose-insulin system the Mixed Meal Model provides a more holistic assessment of metabolic resilience from meal response data, quantifying pre-clinical metabolic deteriorations that drive disease development in overweight and obesity.

Abstract Background Severe anaemia (haemoglobin

Insulin secretion following ingestion of a carbohydrate load affects a multitude of metabolic pathways that simultaneously change direction and quantity of interorgan fluxes of sugars, lipids and amino acids. In the present study, we aimed at identifying markers associated with differential responses to an OGTT a population of healthy adults. By use of three metabolite profiling platforms, we assessed these postprandial responses of a total of 202 metabolites in plasma of 72 healthy volunteers undergoing comprehensive phenotyping and of which half enrolled into a weight-loss program over a three-month period. A standard oral glucose tolerance test (OGTT) served as dietary challenge test to identify changes in postprandial metabolite profiles. Despite classified as healthy according to WHO criteria, two discrete clusters (A and B) were identified based on the postprandial glucose profiles with a balanced distribution of volunteers based on gender and other measures. Cluster A individuals displayed 26% higher postprandial glucose levels, delayed glucose clearance and increased fasting plasma concentrations of more than 20 known biomarkers of insulin resistance and diabetes previously identified in large cohort studies. The volunteers identified by canonical postprandial responses that form cluster A may be called pre-pre-diabetics and defined as “at risk” for development of insulin resistance. Moreover, postprandial changes in selected fatty acids and complex lipids, bile acids, amino acids, acylcarnitines and sugars like mannose revealed marked differences in the responses seen in cluster A and cluster B individuals that sustained over the entire challenge test period of 240 min. Almost all metabolites, including glucose and insulin, returned to baseline values at the end of the test (at 240 min), except a variety of amino acids and here those that have been linked to diabetes development. Analysis of the corresponding metabolite profile in a fasting blood sample may therefore allow for early identification of these subjects at risk for insulin resistance without the need to undergo an OGTT.

Background The global epidemic of type 2 diabetes mellitus (T2DM) renders its prevention a major public health priority. A key risk factor of diabetes is obesity and poor diets. Food environments have been found to influence people’s diets and obesity, positing they may play a role in the prevalence of diabetes. Yet, there is scant evidence on the role they may play in the context of low- and middle-income countries (LMICs). We examined the associations of food environments on T2DM among adults and its heterogeneity by income and sex. Methods and findings We linked individual health outcome data of 12,167 individuals from a network of health surveillance sites (the South Asia Biobank) to the density and proximity of food outlets geolocated around their homes from environment mapping survey data collected between 2018 and 2020 in Bangladesh and Sri Lanka. Density was defined as share of food outlets within 300 m from study participant’s home, and proximity was defined as having at least 1 outlet within 100 m from home. The outcome variables include fasting blood glucose level, high blood glucose, and self-reported diagnosed diabetes. Control variables included demographics, socioeconomic status (SES), health status, healthcare utilization, and physical activities. Data were analyzed in ArcMap 10.3 and STATA 15.1. A higher share of fast-food restaurants (FFR) was associated with a 9.21 mg/dl blood glucose increase (95% CI: 0.17, 18.24; p < 0.05). Having at least 1 FFR in the proximity was associated with 2.14 mg/dl blood glucose increase (CI: 0.55, 3.72; p < 0.01). A 1% increase in the share of FFR near an individual’s home was associated with 8% increase in the probability of being clinically diagnosed as a diabetic (average marginal effects (AMEs): 0.08; CI: 0.02, 0.14; p < 0.05). Having at least 1 FFR near home was associated with 16% (odds ratio [OR]: 1.16; CI: 1.01, 1.33; p < 0.05) and 19% (OR: 1.19; CI: 1.03, 1.38; p < 0.05) increases in the odds of higher blood glucose levels and diagnosed diabetes, respectively. The positive association between FFR density and blood glucose level was stronger among women than men, but the association between FFR proximity and blood glucose level was stronger among men as well as among those with higher incomes. One of the study’s key limitations is that we measured exposure to food environments around residency geolocation; however, participants may source their meals elsewhere. Conclusions Our results suggest that the exposure to fast-food outlets may have a detrimental impact on the risk of T2DM, especially among females and higher-income earners. Policies should target changes in the food environments to promote better diets and prevent T2DM. Dian Kusuma and colleagues investigate the associations between exposure to the density and proximity of healthy and unhealthy food outlets and diabetes in Bangladesh and Sri Lanka. Author summary Why was this study done? With a global prevalence of 9% (463 million people) in 2019, the widespread epidemic of diabetes mellitus renders the prevention of this condition a major priority for public health. Creating health-enabling environments that promote healthy eating and physical activity is needed to reduce the number of people suffering from diabetes. Food environments influence risk factors for type 2 diabetes mellitus (T2DM), but this evidence is understudied among low- and middle-income countries (LMICs). What did the researchers do and find? We examined the associations between the exposure to the density and proximity of healthy and unhealthy food outlets and diabetes (i.e., fasting blood glucose level, high blood glucose, and diagnosed diabetes) using the South Asia Biobank and environment mapping data for 12,167 adults collected between 2018 and 2020 for Bangladesh and Sri Lanka. We found that a higher share of fast-food outlets was associated with a 9.21 mg/dl blood glucose increase. Also, a 1% increase in the share of fast-food outlets was associated with an 8% increase in the probability of being diagnosed with diabetes. Having at least 1 fast-food retailer in the proximity of one’s home was associated with 2.14 mg/dl blood glucose increase. While the association between the density of fast-food retailers and blood glucose level was stronger among women than men, density of fast-food restaurants (FFRs) increased the likelihood of being diagnosed with diabetes for both men and women. The association between proximity to these outlets and blood glucose level was stronger among men. Both density and proximity of fast-food outlets were associated with diabetes outcomes among high-income earners. Density of FFRs was associated with increased probability of being diagnosed with diabetes for low-income earners, although the effect size was smaller than for high-income earners. What do these findings mean? The exposure to fast-food outlets may have a detrimental impact on the risk of diabetes, especially among females and those with higher income. Policies should target changes in the food environments to promote better diets and prevent diabetes.

Introduction: In low-middle income countries (LMICs) the role of food environments on obesity has been understudied. We address this gap by 1) examining the effect of food environments on adults’ body size (BMI, waist circumference) and obesity; 2) measuring the heterogeneity of such effects by income and sex. Methods: This cross-sectional study analysed South Asia Biobank surveillance and environment mapping data for 12,167 adults collected between 2018 and 2020 from 33 surveillance sites in Bangladesh and Sri Lanka. Individual-level data (demographic, socio-economic, and health characteristics) were combined with exposure to healthy and unhealthy food environments measured with geolocations of food outlets (obtained through ground-truth surveys) within 300 m buffer zones around participants' homes. Multivariate regression models were used to assess association of exposure to healthy and unhealthy food environments on waist circumference, BMI, and probability of obesity for the total sample and stratified by sex and income. Findings: The presence of a higher share of supermarkets in the neighbourhood was associated with a reduction in body size (BMI, β = - 3∙23; p

Summary: Case fatality among African children with severe acute malnutrition remains high. We report a 3-arm pilot trial in 58 Ugandan children, comparing feeds targeting disordered gastrointestinal function containing cowpea (CpF, n = 20) or inulin (InF, n = 20) with conventional feeds (ConF, n = 18). Baseline measurements of gut permeability (lactulose:mannitol ratio 1.19 ± SD 2.00), inflammation (fecal calprotectin 539.0 μg/g, interquartile range [IQR] 904.8), and satiety (plasma polypeptide YY 62.6 pmol/l, IQR 110.3) confirm gastrointestinal dysfunction. By day 28, no differences are observable in proportion achieving weight gain >5 g/kg/day (87%, 92%, 86%; p > 0.05), mortality (16%, 30%, 17%; p > 0.05), or edema resolution (83%, 54%, 91%; p > 0.05) among CpF, InF, and ConF. Decreased fecal bacterial richness from day 1 (abundance-based coverage estimator [ACE] 53.2) to day 7 (ACE 40.8) is observed only in ConF (p = 0.025). Bifidobacterium relative abundance increases from day 7 (5.8% ± 8.6%) to day 28 (10.9% ± 8.7%) in CpF (corrected p = 1.000). Legume-enriched feeds support aspects of gut function and the microbiome. Trial registration PACTR201805003381361.

Abstract Background Childhood overweight and obesity is a serious public health issue with an increase being observed in preschool-aged children. Treating childhood obesity is difficult and few countries use standardized treatments. Therefore, there is a need to find effective approaches that are feasible for both health care providers and families. Thus, the overall aim of this study is to assess the acceptance and effectiveness of a parent support program (the More and Less, ML) for the management of overweight and obesity followed by a mobile health (mHealth) program (the MINISTOP application) in a socially diverse population of families. Methods/design A two-arm, parallel design randomized controlled trial in 300 2-to 6-year-old children with overweight and obesity from Romania, Spain and Sweden (n = 100 from each). Following baseline assessments children are randomized into the intervention or control group in a 1:1 ratio. The intervention, the ML program, consists of 10-weekly group sessions which focus on evidence-based parenting practices, followed by the previously validated MINISTOP application for 6-months to support healthy eating and physical activity behaviors. The primary outcome is change in body mass index (BMI) z-score after 9-months and secondary outcomes include: waist circumference, eating behavior (Child Eating Behavior Questionnaire), parenting behavior (Comprehensive Feeding Practices Questionnaire), physical activity (ActiGraph wGT3x-BT), dietary patterns (based on metabolic markers from urine and 24 h dietary recalls), epigenetic and gut hormones (fasting blood samples), and the overall acceptance of the overweight and obesity management in young children (semi-structured interviews). Outcomes are measured at baseline and after: 10-weeks (only BMI z-score, waist circumference), 9-months (all outcomes), 15- and 21-months (all outcomes except physical activity, dietary patterns, epigenetics and gut hormones) post-baseline. Discussion This study will evaluate a parent support program for weight management in young children in three European countries. To boost the effect of the ML program the families will be supported by an app for 6-months. If the program is found to be effective, it has the potential to be implemented into routine care to reduce overweight and obesity in young children and the app could prove to be a viable option for sustained effects of the care provided. Trial registration ClinicalTrials.gov NCT03800823; 11 Jan 2019.

Malnutrition, including both undernutrition and obesity, is a significant problem in low- and middle-income countries (LMICs). In order to study malnutrition and develop effective intervention strategies, it is crucial to evaluate nutritional status in LMICs at the individual, household, and community levels. In a multinational research project supported by the Bill & Melinda Gates Foundation, we have been using a wearable technology to conduct objective dietary assessment in sub-Saharan Africa. Our assessment includes multiple diet-related activities in urban and rural families, including food sources (e.g., shopping, harvesting, and gathering), preservation/storage, preparation, cooking, and consumption (e.g., portion size and nutrition analysis). Our wearable device (“eButton” worn on the chest) acquires real-life images automatically during wake hours at preset time intervals. The recorded images, in amounts of tens of thousands per day, are post-processed to obtain the information of interest. Although we expect future Artificial Intelligence (AI) technology to extract the information automatically, at present we utilize AI to separate the acquired images into two binary classes: images with (Class 1) and without (Class 0) edible items. As a result, researchers need only to study Class-1 images, reducing their workload significantly. In this paper, we present a composite machine learning method to perform this classification, meeting the specific challenges of high complexity and diversity in the real-world LMIC data. Our method consists of a deep neural network (DNN) and a shallow learning network (SLN) connected by a novel probabilistic network interface layer. After presenting the details of our method, an image dataset acquired from Ghana is utilized to train and evaluate the machine learning system. Our comparative experiment indicates that the new composite method performs better than the conventional deep learning method assessed by integrated measures of sensitivity, specificity, and burden index, as indicated by the Receiver Operating Characteristic (ROC) curve.

Background: Roux-en-Y gastric bypass is recognised as a standard of care in the treatment of diabetes mellitus and obesity. However, the optimal length of the Roux-en-Y gastric bypass limbs remains controversial, with substantial variation in practice. Specifically, a longer biliopancreatic limb length of 150 cm (‘long limb’) has been hypothesised to be better for the treatment of diabetes mellitus because it increases the postprandial secretion of gut hormones, such as glucagon-like peptide 1, and increases insulin sensitivity, compared with the Roux-en-Y gastric bypass utilising a standard biliopancreatic limb length of 50 cm (‘standard limb’). Objective: To evaluate the mechanisms, clinical efficacy and safety of long limb versus the standard limb Roux-en-Y gastric bypass in patients undergoing metabolic surgery for obesity and diabetes mellitus. Design: A double-blind, mechanistic randomised controlled trial was conducted to evaluate the mechanisms, clinical efficacy and safety of the two interventions. Setting: Imperial College London, King’s College London and their associated NHS trusts. Participants: Patients with obesity and type 2 diabetes mellitus who were eligible for metabolic surgery. Interventions: Participants were randomly assigned (1 : 1) to 150-cm (long limb) or 50-cm (standard limb) biliopancreatic limb Roux-en-Y gastric bypass with a fixed alimentary limb of 100 cm. The participants underwent meal tolerance tests to measure glucose excursions, glucagon-like peptide 1 and insulin secretion, and hyperinsulinaemic–euglycaemic clamps with stable isotopes to measure insulin sensitivity preoperatively, at 2 weeks after the surgery and at matched 20% total body weight loss. Clinical follow-up continued up to 1 year. Main outcome measures: Primary – postprandial peak of active glucagon-like peptide 1 concentration at 2 weeks after intervention. Secondary – fasting and postprandial glucose and insulin concentrations, insulin sensitivity, glycaemic control and weight loss at 12 months after surgery, and safety of participants. Results: Of the 53 participants randomised, 48 completed the trial. There were statistically significant decreases in fasting and postprandial glucose concentrations, increases in insulin, glucagon-like peptide 1 secretion and insulin sensitivity, and reductions in the levels of glycated haemoglobin (i.e. HbA1c) and weight in both long and standard limb groups. However, there were no significant differences between trial groups in any of these parameters. Limitations: The main limitations of this trial include the relatively short follow-up of 12 months and elongation of the biliopancreatic limb to a fixed length of 150 cm. Conclusion: Patients undergoing both types of Roux-en-Y gastric bypass benefited metabolically from the surgery. The results have not demonstrated that elongation of the biliopancreatic limb of the Roux-en-Y gastric bypass from 50 to 150 cm results in superior metabolic outcomes in terms of glucose excursions, insulin and incretin hormone secretion, and insulin sensitivity, when assessed at up to 12 months after surgery. Future work: Continued longitudinal follow-up of the long and standard limb cohorts will be necessary to evaluate any differential effects of the two surgical procedures on patients’ metabolic trajectories. Trial registration: Current Controlled Trials ISRCTN15283219. Funding: This project was funded by the Efficacy and Mechanism Evaluation programme, a Medical Research Council and National Institute for Health Research (NIHR) partnership. This will be published in full in Efficacy and Mechanism Evaluation; Vol. 8, No. 3. See the NIHR Journals Library website for further project information. The section in the report on endocrinology and investigative medicine is funded by grants from the Medical Research Council, the Biotechnology and Biological Sciences Research Council, NIHR, an Integrative Mammalian Biology Capacity Building Award and a FP7-HEALTH-2009-241592 EuroCHIP grant. This section is also supported by the NIHR Biomedical Research Centre Funding Scheme.

Knowing the amounts of energy and nutrients in an individual’s diet is important for maintaining health and preventing chronic diseases. As electronic and AI technologies advance rapidly, dietary assessment can now be performed using food images obtained from a smartphone or a wearable device. One of the challenges in this approach is to computationally measure the volume of food in a bowl from an image. This problem has not been studied systematically despite the bowl being the most utilized food container in many parts of the world, especially in Asia and Africa. In this paper, we present a new method to measure the size and shape of a bowl by adhering a paper ruler centrally across the bottom and sides of the bowl and then taking an image. When observed from the image, the distortions in the width of the paper ruler and the spacings between ruler markers completely encode the size and shape of the bowl. A computational algorithm is developed to reconstruct the three-dimensional bowl interior using the observed distortions. Our experiments using nine bowls, colored liquids, and amorphous foods demonstrate high accuracy of our method for food volume estimation involving round bowls as containers. A total of 228 images of amorphous foods were also used in a comparative experiment between our algorithm and an independent human estimator. The results showed that our algorithm overperformed the human estimator who utilized different types of reference information and two estimation methods, including direct volume estimation and indirect estimation through the fullness of the bowl.

The short chain fatty acids (SCFAs) acetate, butyrate and propionate, are produced by fermentation of non-digestible carbohydrates by the gut microbiota and regulate appetite, adiposity, metabolism, glycemic control, and immunity. SCFAs act at two distinct G protein coupled receptors (GPCRs), FFAR2 and FFAR3 and are expressed in intestinal enteroendocrine cells (EECs), where they mediate anorectic gut hormone release. EECs also express other GPCRs that act as nutrient sensors, thus SCFAs may elicit some of their health-promoting effects by altering GPCR expression in EECs and enhance gut sensitivity to dietary molecules. Here, we identify that exposure of the murine EEC STC-1 cell line or intestinal organoids to physiological concentrations of SCFAs enhances mRNA levels of the umami taste receptors TASR1 and TASR3, without altering levels of the SCFA GPCRs, FFAR2 and FFAR3. Treatment of EECs with propionate or butyrate, but not acetate, increased levels of umami receptor transcripts, while propionate also reduced CCK expression. This was reversed by inhibiting Gαi/o signaling with pertussis toxin, suggesting that SCFAs act through FFAR2/3 to alter gene expression. Surprisingly, neither a FFAR3 nor a FFAR2 selective ligand could increase TASR1/TASR3 mRNA levels. We assessed the functional impact of increased TASR1/TASR3 expression using unique pharmacological properties of the umami taste receptor; namely, the potentiation of signaling by inosine monophosphate. Activation of umami taste receptor induced inositol-1-phosphate and calcium signaling, and butyrate pretreatment significantly enhanced such signaling. Our study reveals that SCFAs may contribute to EEC adaptation and alter EEC sensitivity to bioactive nutrients.

Summary: The ability of propionate, a short-chain fatty acid produced from the fermentation of non-digestible carbohydrates in the colon, to stimulate the release of anorectic gut hormones, such as glucagon like peptide-1 (GLP-1), is an attractive approach to enhance appetite regulation, weight management, and glycemic control. Propionate induces GLP-1 release via its G protein-coupled receptor (GPCR), free fatty acid receptor 2 (FFA2), a GPCR that activates Gαi and Gαq/11. However, how pleiotropic GPCR signaling mechanisms in the gut regulates appetite is poorly understood. Here, we identify propionate-mediated G protein signaling is spatially directed within the cell whereby FFA2 is targeted to very early endosomes. Furthermore, propionate activates a Gαi/p38 signaling pathway, which requires receptor internalization and is essential for propionate-induced GLP-1 release in enteroendocrine cells and colonic crypts. Our study reveals that intestinal metabolites engage membrane trafficking pathways and that receptor internalization could orchestrate complex GPCR pathways within the gut.

Summary: Background: Dietary advice remains the cornerstone of prevention and management of type 2 diabetes (T2D). However, understanding the efficacy of dietary interventions is confounded by the challenges inherent in assessing free living diet. Here we profiled dietary metabolites to investigate glycaemic deterioration and cardiometabolic risk in people at risk of or living with T2D. Methods: We analysed data from plasma collected at baseline and 18-month follow-up in individuals from the Innovative Medicines Initiative (IMI) Diabetes Research on Patient Stratification (DIRECT) cohort 1 n = 403 individuals with normal or impaired glucose regulation (prediabetic) and cohort 2 n = 458 individuals with new onset of T2D. A dietary metabolite profile model (Tpred) was constructed using multivariable regression of 113 plasma metabolites obtained from targeted metabolomics assays. The continuous Tpred score was used to explore the relationships between diet, glycaemic deterioration and cardio-metabolic risk via multiple linear regression models. Findings: A higher Tpred score was associated with healthier diets high in wholegrain (β=3.36 g, 95% CI 0.31, 6.40 and β=2.82 g, 95% CI 0.06, 5.57) and lower energy intake (β=-75.53 kcal, 95% CI -144.71, -2.35 and β=-122.51 kcal, 95% CI -186.56, -38.46), and saturated fat (β=-0.92 g, 95% CI -1.56, -0.28 and β=–0.98 g, 95% CI -1.53, -0.42 g), respectively for cohort 1 and 2. In both cohorts a higher Tpred score was also associated with lower total body adiposity and favourable lipid profiles HDL-cholesterol (β=0.07 mmol/L, 95% CI 0.03, 0.1), (β=0.08 mmol/L, 95% CI 0.04, 0.1), and triglycerides (β=-0.1 mmol/L, 95% CI -0.2, -0.03), (β=-0.2 mmol/L, 95% CI -0.3, -0.09), respectively for cohort 1 and 2. In cohort 2, the Tpred score was negatively associated with liver fat (β=-0.74%, 95% CI -0.67, -0.81), and lower fasting concentrations of HbA1c (β=-0.9 mmol/mol, 95% CI -1.5, -0.1), glucose (β=-0.2 mmol/L, 95% CI -0.4, -0.05) and insulin (β=-11.0 pmol/mol, 95% CI -19.5, -2.6). Longitudinal analysis showed at 18-month follow up a higher Tpred score was also associated lower total body adiposity in both cohorts and lower fasting glucose (β=-0.2 mmol/L, 95% CI -0.3, -0.01) and insulin (β=-9.2 pmol/mol, 95% CI -17.9, -0.4) concentrations in cohort 2. Interpretation: Plasma dietary metabolite profiling provides objective measures of diet intake, showing a relationship to glycaemic deterioration and cardiometabolic health. Funding: This work was supported by the Innovative Medicines Initiative Joint Undertaking under grant agreement no. 115,317 (DIRECT), resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007–2013) and EFPIA companies.

BackgroundNon-alcoholic fatty liver disease (NAFLD) is highly prevalent and causes serious health complications in individuals with and without type 2 diabetes (T2D). Early diagnosis of NAFLD is important, as this can help prevent irreversible damage to the liver and, ultimately, hepatocellular carcinomas. We sought to expand etiological understanding and develop a diagnostic tool for NAFLD using machine learning.Methods and findingsWe utilized the baseline data from IMI DIRECT, a multicenter prospective cohort study of 3,029 European-ancestry adults recently diagnosed with T2D (n = 795) or at high risk of developing the disease (n = 2,234). Multi-omics (genetic, transcriptomic, proteomic, and metabolomic) and clinical (liver enzymes and other serological biomarkers, anthropometry, measures of beta-cell function, insulin sensitivity, and lifestyle) data comprised the key input variables. The models were trained on MRI-image-derived liver fat content (ConclusionsIn this study, we developed several models with different combinations of clinical and omics data and identified biological features that appear to be associated with liver fat accumulation. In general, the clinical variables showed better prediction ability than the complex omics variables. However, the combination of omics and clinical variables yielded the highest accuracy. We have incorporated the developed clinical models into a web interface (see: https://www.predictliverfat.org/) and made it available to the community.Trial registrationClinicalTrials.gov NCT03814915.

Objective: Dietary supplementation with fermentable carbohydrate protects against body weight gain. Fermentation by the resident gut microbiota produces short-chain fatty acids, which act at free fatty acid receptor 2 (FFAR2). Our aim was to test the hypothesis that FFAR2 is important in regulating the beneficial effects of fermentable carbohydrate on body weight and to understand the role of gut hormones PYY and GLP-1. Methods: Wild-type or Ffar2−/− mice were fed an inulin supplemented or control diet. Mice were metabolically characterized and gut hormone concentrations, enteroendocrine cell density measurements were carried out. Intestinal organoids and colonic cultures were utilized to substantiate the in vivo findings. Results: We provide new mechanistic insight into how fermentable carbohydrate regulates metabolism. Using mice that lack FFAR2, we demonstrate that the fermentable carbohydrate inulin acts via this receptor to drive an 87% increase in the density of cells that produce the appetite-suppressing hormone peptide YY (PYY), reduce food intake, and prevent diet-induced obesity. Conclusion: Our results demonstrate that FFAR2 is predominantly involved in regulating the effects of fermentable carbohydrate on metabolism and does so, in part, by enhancing PYY cell density and release. This highlights the potential for targeting enteroendocrine cell differentiation to treat obesity. Keywords: Obesity, Diet, Peptide YY, Microbiota, Colon

Introduction: A major component of the digesta reaching the colon from the distal ileum is carbohydrate. This carbohydrate is subject to microbial fermentation and can radically change bacterial populations in the colon and the metabolites they produce, particularly short-chain fatty acids (SCFA). However, very little is currently known about the forms and levels of carbohydrate in the ileum and the composition of the ileal microbiota in humans. Most of our current understanding of carbohydrate that is not absorbed by the small intestine comes from ileostomy models, which may not reflect the physiology of an intact gastrointestinal tract. Methods: We will investigate how ileal content changes depending on diet using a randomised crossover study in healthy humans. Participants will be inpatients at the research facility for three separate 4-day visits. During each visit, participants will consume one of three diets, which differ in carbohydrate quality: 1) low-fibre refined diet; 2) high-fibre diet with intact cellular structures; 3) high-fibre diet where the cellular structures have been disrupted (e.g. milling, blending). On day 1, a nasoenteric tube will be placed into the distal ileum and its position confirmed under fluoroscopy. Ileal samples will be collected via the nasoenteric tube and metabolically profiled, which will determine the amount and type of carbohydrate present, and the composition of the ileal microbiota will be measured. Blood samples will be collected to assess circulating hormones and metabolites. Stool samples will be collected to assess faecal microbiota composition. Subjective appetite measures will be collected using visual analogue scales. Breath hydrogen will be measured in real-time as a marker of intestinal fermentation. Finally, an in vitro continuous fermentation model will be inoculated with ileal fluid in order to understand the shift in microbial composition and SCFA produced in the colon following the different diets. Registration: ISRCTN11327221.

Summary: Background: Severe anaemia is a leading cause of paediatric admission to hospital in Africa; post-discharge outcomes remain poor, with high 6-month mortality (8%) and re-admission (17%). We aimed to investigate post-discharge interventions that might improve outcomes. Methods: Within the two-stratum, open-label, multicentre, factorial randomised TRACT trial, children aged 2 months to 12 years with severe anaemia, defined as haemoglobin of less than 6 g/dL, at admission to hospital (three in Uganda, one in Malawi) were randomly assigned, using sequentially numbered envelopes linked to a second non-sequentially numbered set of allocations stratified by centre and severity, to enhanced nutritional supplementation with iron and folate-containing multivitamin multimineral supplements versus iron and folate alone at treatment doses (usual care), and to co-trimoxazole versus no co-trimoxazole. All interventions were administered orally and were given for 3 months after discharge from hospital. Separately reported randomisations investigated transfusion management. The primary outcome was 180-day mortality. All analyses were done in the intention-to-treat population; follow-up was 180 days. This trial is registered with the International Standard Randomised Controlled Trial registry, ISRCTN84086586, and follow-up is complete. Findings: From Sept 17, 2014, to May 15, 2017, 3983 eligible children were randomly assigned to treatment, and followed up for 180 days. 164 (4%) were lost to follow-up. 1901 (95%) of 1997 assigned multivitamin multimineral supplement, 1911 (96%) of 1986 assigned iron and folate, and 1922 (96%) of 1994 assigned co-trimoxazole started treatment. By day 180, 166 (8%) children in the multivitamin multimineral supplement group versus 169 (9%) children in the iron and folate group had died (hazard ratio [HR] 0·97, 95% CI 0·79–1·21; p=0·81) and 172 (9%) who received co-trimoxazole versus 163 (8%) who did not receive co-trimoxazole had died (HR 1·07, 95% CI 0·86–1·32; p=0·56). We found no evidence of interactions between these randomisations or with transfusion randomisations (p>0·2). By day 180, 489 (24%) children in the multivitamin multimineral supplement group versus 509 (26%) children in the iron and folate group (HR 0·95, 95% CI 0·84–1·07; p=0·40), and 500 (25%) children in the co-trimoxazole group versus 498 (25%) children in the no co-trimoxazole group (1·01, 0·89–1·15; p=0·85) had had one or more serious adverse events. Most serious adverse events were re-admissions, occurring in 692 (17%) children (175 [4%] with at least two re-admissions). Interpretation: Neither enhanced supplementation with multivitamin multimineral supplement versus iron and folate treatment or co-trimoxazole prophylaxis improved 6-month survival. High rates of hospital re-admission suggest that novel interventions are urgently required for severe anaemia, given the burden it places on overstretched health services in Africa. Funding: Medical Research Council and Department for International Development.

Abstract Introduction Type 2 diabetes (T2D) is multifactorial involving lifestyle, environmental and genetic risk factors. This study aims to investigate the impact of genetic interactions with alcohol and diet quality on glycated haemoglobin A1c (HbA1c) independent of obesity, in a British population. Methods Cross‐sectional study of 14 089 white British participants from Airwave Health Monitoring Study and a subsample of 3733 participants with dietary data. A T2D genetic risk score (GRS) was constructed, and its interactions with diet on HbA1c were assessed. Results GRS was associated with a higher HbA1c% (β = 0.03, P

Food reformulation policies aimed at reducing the risk of diet-related non-communicable diseases have been implemented in many countries. The degree of success of reformulation policies in changing the range of food options available to consumers has been a function of the design of these policies. Our objective was to review the different factors making the design and implementation of a food reformulation policy effective at improving populations’ diets and health. In this narrative review, we present a logic model of the action of reformulation policies on consumer behaviour, dietary intake and population health. We set out how policy design could drive outcomes, and highlight the role for governments and public health agencies in promoting food reformulation that is effective in improving diet and health. The key drivers of success for reformulation policies include strong incentives, a tight implementation strategy, a focus on the overall nutritional quality of food products, rather than on individual nutrients, and effective monitoring and evaluation. Additionally, policies should mark the distinction between product reformulation and product differentiation, which have different nutrition and health outcomes.

There is extensive information of the beneficial effects of virgin olive oil (VOO), especially on cardiovascular diseases. Some VOO healthy properties have been attributed to their phenolic-compounds (PCs). The aim of this review is to present updated data on the effects of olive oil (OO) PCs on the gut microbiota, lipid metabolism, immune system, and obesity, as well as on the crosstalk among them. We summarize experiments and clinical trials which assessed the specific effects of the olive oil phenolic-compounds (OOPCs) without the synergy with OO-fats. Several studies have demonstrated that OOPC consumption increases Bacteroidetes and/or reduces the Firmicutes/Bacteroidetes ratio, which have both been related to atheroprotection. OOPCs also increase certain beneficial bacteria and gut-bacteria diversity which can be therapeutic for lipid-immune disorders and obesity. Furthermore, some of the mechanisms implicated in the crosstalk between OOPCs and these disorders include antimicrobial-activity, cholesterol microbial metabolism, and metabolites produced by bacteria. Specifically, OOPCs modulate short-chain fatty-acids produced by gut-microbiota, which can affect cholesterol metabolism and the immune system, and may play a role in weight gain through promoting satiety. Since data in humans are scarce, there is a necessity for more clinical trials designed to assess the specific role of the OOPCs in this crosstalk.

Background: Changes in intestinal mucosal integrity and gut microbial balance occur in severe acute malnutrition (SAM), resulting in treatment failure and adverse clinical outcomes (gram-negative sepsis, diarrhoea and high case-fatality). Transient lactose intolerance, due to loss of intestinal brush border lactase, also complicates SAM, thus milk based feeds may not be optimal for nutritional rehabilitation. Since the gut epithelial barrier can be supported by short chain fatty acids, derived from microbiota fermentation by particular fermentable carbohydrates, we postulated that an energy-dense nutritional feed comprising of legume-based fermentable carbohydrates, incorporated with lactose-free versions of standard World Health Organization (WHO) F75/F100 nutritional feeds will enhance epithelial barrier function in malnourished children, reduce and promote resolution of diarrhoea and improve overall outcome. Methods: We will investigate in an open-label trial in 160 Ugandan children with SAM, defined by mid-upper arm circumference 5 g/kg/day), ii) de novo development of diarrhoea (>3 loose stools/day), iii) time to diarrhoea resolution (if >3 loose stools/day), and iv) time to oedema resolution (if kwashiorkor) and change in intestinal biomarkers (faecal calprotectin). Discussion: We hypothesize that, if introduced early in the management of malnutrition, such lactose-free, fermentable carbohydrate-based feeds, could safely and cheaply improve global outcome by reducing lactose intolerance-related diarrhoea, improving mucosal integrity and enhancing immunity, and limiting the risk of systemic infection and associated broad-spectrum antibiotic resistance. Registration: ISRCTN 10309022.

The purpose of this study was to investigate the associations between intakes of fibre from the main food sources of fibre in the UK diet with body mass index (BMI), percentage body fat (%BF), waist circumference (WC) and C-reactive protein (CRP). Participants enrolled in the Airwave Health Monitoring Study (2007−2012) with 7-day food records (n = 6898; 61% men) were included for cross-sectional analyses. General linear models evaluated associations across fifths of fibre intakes (total, vegetable, fruit, potato, whole grain and non-whole grain cereal) with BMI, %BF, WC and CRP. Fully adjusted analyses showed inverse linear trends across fifths of total fibre and fibre from fruit with all outcome measures (ptrend < 0.0001). Vegetable fibre intake showed an inverse association with WC (ptrend 0.0156) and CRP (ptrend 0.0005). Fibre from whole grain sources showed an inverse association with BMI (ptrend 0.0002), %BF (ptrend 0.0007) and WC (ptrend 0.0004). Non-whole grain cereal fibre showed an inverse association with BMI (Ptrend 0.0095). Direct associations observed between potato fibre intake and measures of body composition and inflammation were attenuated in fully adjusted analyses controlling for fried potato intake. Higher fibre intake has a beneficial association on body composition, however, there are differential associations based on the food source.

Introduction Current dietary assessment methods face challenges in accurately capturing individuals’ dietary habits, undermining the efficacy of public health strategies. The ‘Standardised and Objective Dietary Intake Assessment Tool’ (SODIAT)-1 study aims to assess the effectiveness of three emerging technologies (urine and capillary blood biomarkers, and wearable camera technology) and two online self-reporting dietary assessment tools to monitor dietary intake. Methods This randomised controlled crossover trial will recruit 30 participants (aged 18-70 years and BMI of 20-30 kg/m 2) from Imperial College London and the University of Reading. Exclusion criteria include recent weight change, food allergies/intolerances, following restrictive diets, certain health conditions and medication use. Interested volunteers will be directed to an online screening questionnaire via REDCap and eligible participants will attend a pre-study visit. Volunteers will consume, in a random order, two highly-controlled diets (compliant and non-compliant with UK guidelines) for four days each. Each study arm will be separated by at least one-week. During each test period, dietary intake will be monitored continuously using wearable cameras and self-recorded using eNutri (food frequency questionnaire) and Intake24 (24-hour dietary recall). Urine and capillary blood samples will be collected for biomarker analysis. Data analysis will assess the accuracy of dietary reporting across these methods using Lin’s concordance correlation coefficient. Discussion and ethical considerations This study introduces a novel approach to dietary assessment, addressing the limitations of traditional methods by reducing misreporting and enhancing inclusivity, particularly for underrepresented populations with literacy or language barriers. However, challenges persist, such as variability in biomarker data due to failure to adhere to sample storage requirements and the practicalities of continuously wearing cameras. To protect privacy, participants will be instructed to remove cameras at inappropriate times, and artificial intelligence will be used to blur all images captured apart from food.

Background Environmental enteropathy (EE) is a highly prevalent subclinical inflammatory intestinal disorder associated with growth failure, impaired neurocognitive development, poor response to oral vaccines, and micronutrient deficiencies. However, EE research and clinical trials are hampered by the lack of non-invasive tools for measuring intestinal function in detail. This study aims to develop new tools for the measurement of multiple domains of gut functional capacity. Methods The GI TOOLS project is a cross-sectional study that will recruit adults aged 18-65 years with EE in Lusaka, Zambia. Each participant will undergo assessment of gut functional capacity using novel near-point-of-care tools and provide multiple samples for detailed laboratory analyses. Participants will also undergo endoscopy for collection of duodenal biopsies. Novel techniques include stable isotopes approaches to measuring digestion, absorption, and bidirectional transmucosal amino acid flux, a non-invasive fluorescence tool for real-time evaluation of gut permeability, and assessment of reverse permeation of intravenous antibiotics to be carried out separately in Zimbabwe. Stool and duodenal microbiome sequencing using MinION sequencing, metabolome analysis applied to plasma and intestinal fluids, blood immune cell phenotyping, in vitro epithelial barrier models, and duodenal immunohistochemistry will also be used to explore EE in depth. These will all be integrated with gold standard histology and mucosal morphometry, alongside lactulose permeation data, and stool and plasma biomarker analysis. The protocol has been approved by ethics committees and regulators in Zambia, Zimbabwe, and the UK. Participants will give informed consent before they can participate Anticipated outcomes Based on this extensive phenotyping, tests will be developed which can be simplified and refined for use in adults and children with EE, and for clinical trials. Findings from this project will be disseminated through in-person meetings with caregivers and regulatory bodies, presentations at conferences and in peer-reviewed journals.

BACKGROUND:Obesity is rising at an alarming rate globally. Different fermentable carbohydrates have been shown to reduce obesity. The aim of the present study was to investigate if two different fermentable carbohydrates (inulin and β-glucan) exert similar effects on body composition and central appetite regulation in high fat fed mice. METHODOLOGY/PRINCIPAL FINDINGS:Thirty six C57BL/6 male mice were randomized and maintained for 8 weeks on a high fat diet containing 0% (w/w) fermentable carbohydrate, 10% (w/w) inulin or 10% (w/w) β-glucan individually. Fecal and cecal microbial changes were measured using fluorescent in situ hybridization, fecal metabolic profiling was obtained by proton nuclear magnetic resonance ((1)H NMR), colonic short chain fatty acids were measured by gas chromatography, body composition and hypothalamic neuronal activation were measured using magnetic resonance imaging (MRI) and manganese enhanced MRI (MEMRI), respectively, PYY (peptide YY) concentration was determined by radioimmunoassay, adipocyte cell size and number were also measured. Both inulin and β-glucan fed groups revealed significantly lower cumulative body weight gain compared with high fat controls. Energy intake was significantly lower in β-glucan than inulin fed mice, with the latter having the greatest effect on total adipose tissue content. Both groups also showed an increase in the numbers of Bifidobacterium and Lactobacillus-Enterococcus in cecal contents as well as feces. β-Glucan appeared to have marked effects on suppressing MEMRI associated neuronal signals in the arcuate nucleus, ventromedial hypothalamus, paraventricular nucleus, periventricular nucleus and the nucleus of the tractus solitarius, suggesting a satiated state. CONCLUSIONS/SIGNIFICANCE:Although both fermentable carbohydrates are protective against increased body weight gain, the lower body fat content induced by inulin may be metabolically advantageous. β-Glucan appears to suppress neuronal activity in the hypothalamic appetite centers. Differential effects of fermentable carbohydrates open new possibilities for nutritionally targeting appetite regulation and body composition.

BACKGROUND:Adipose tissue patterning has a major influence on the risk of developing chronic disease. Environmental influences on both body fat patterning and appetite regulation are not fully understood. This study was performed to investigate the impact of resistant starch (RS) on adipose tissue deposition and central regulation of appetite in mice. METHODOLOGY AND PRINCIPLE FINDINGS:Forty mice were randomised to a diet supplemented with either the high resistant starch (HRS), or the readily digestible starch (LRS). Using (1)H magnetic resonance (MR) methods, whole body adiposity, intrahepatocellular lipids (IHCL) and intramyocellular lipids (IMCL) were measured. Manganese-enhanced MRI (MEMRI) was used to investigate neuronal activity in hypothalamic regions involved in appetite control when fed ad libitum. At the end of the interventional period, adipocytes were isolated from epididymal adipose tissue and fasting plasma collected for hormonal and adipokine measurement. Mice on the HRS and LRS diet had similar body weights although total body adiposity, subcutaneous and visceral fat, IHCL, plasma leptin, plasma adiponectin plasma insulin/glucose ratios was significantly greater in the latter group. Adipocytes isolated from the LRS group were significantly larger and had lower insulin-stimulated glucose uptake. MEMRI data obtained from the ventromedial and paraventricular hypothalamic nuclei suggests a satiating effect of the HRS diet despite a lower energy intake. CONCLUSION AND SIGNIFICANCE:Dietary RS significantly impacts on adipose tissue patterning, adipocyte morphology and metabolism, glucose and insulin metabolism, as well as affecting appetite regulation, supported by changes in neuronal activity in hypothalamic appetite regulation centres which are suggestive of satiation.

Introduction: Overweight and obesity affects over 70% of the UK population and is a major risk factor for the development of co-morbidities, including type 2 diabetes and cardiovascular disease. There now exists a considerable evidence base for the management of obesity. However, this is not the case for the prevention of obesity. Preventing weight gain in periods of life where there is an elevated risk of fat mass expansion could be beneficial to preventing associated diseases in later life. This protocol investigates the impact of novel food ingredient inulin propionate ester (IPE) in the prevention of weight gain. This trial aims to investigate the primary hypothesis that IPE has a superior effect on preventing body weight gain, compared with inulin, in young ( Methods: In this multi-centre, double-blind, randomised, parallel-group study, eligible participants will be randomly assigned to consume 10g IPE or 10g inulin (control) daily for 12 months. Study visits will be conducted at baseline, two-month, six-month and 12-month time points. The primary outcome is weight gain from baseline to 12 months. Secondary outcomes will examine changes in metabolic and cardiovascular health biomarkers, body composition and appetite. A mechanistic sub-group will explore causal mechanisms around energy balance, body composition, appetite regulation and the gut microbiota. Based on the power calculation, the sample size required is 270 participants or 135 per study group. Ethics and dissemination: The trial protocol and participant-facing documents have been reviewed and approved, by the London Hampstead Ethics Committee (REC Reference 19/LO/0095, 29 th January 2019). Upon completion, the trial results will be published in peer-reviewed journals and presented at scientific conferences. Trial registration number: ISRCTN16299902, 1 st March 2018.

Objective To examine the effect of the consumption of ultraprocessed food on diet quality, and cardiometabolic risk (CMR) in an occupational cohort.Design Cross-sectional.Setting Occupational cohort.Participants 53 163 British police force employees enrolled (2004–2012) into the Airwave Health Monitoring Study. A total of 28 forces across the UK agreed to participate. 9009 participants with available 7-day diet record data and complete co-variate data are reported in this study.Main outcome measures A CMR and Dietary Approaches to Stop Hypertension score were treated as continuous variables and used to generate measures of cardiometabolic health and diet quality. Secondary outcome measures include percentage of energy from fat, saturated fat, carbohydrate, protein and non-milk extrinsic sugars (NMES) and fibre grams per 1000 kcal of energy intake.Results In this cohort, 58.3%±11.6 of total energy intake was derived from ultraprocessed (NOVA 4) foods. Ultraprocessed food intake was negatively correlated with diet quality (r=−0.32, p

Introduction: A major component of the digesta reaching the colon from the distal ileum is carbohydrate. This carbohydrate is subject to microbial fermentation and can radically change bacterial populations in the colon and the metabolites they produce, particularly short-chain fatty acids (SCFA). However, very little is currently known about the forms and levels of carbohydrate in the ileum and the composition of the ileal microbiota in humans. Most of our current understanding of carbohydrate that is not absorbed by the small intestine comes from ileostomy models, which may not reflect the physiology of an intact gastrointestinal tract. Methods: We will investigate how ileal content changes depending on diet using a randomised crossover study in healthy humans. Participants will be inpatients at the research facility for three separate 4-day visits. During each visit, participants will consume one of three diets, which differ in carbohydrate quality: 1) low-fibre refined diet; 2) high-fibre diet with intact cellular structures; 3) high-fibre diet where the cellular structures have been disrupted (e.g. milling, blending). On day 1, a nasoenteric tube will be placed into the distal ileum and its position confirmed under fluoroscopy. Ileal samples will be collected via the nasoenteric tube and metabolically profiled, which will determine the amount and type of carbohydrate present, and the composition of the ileal microbiota will be measured. Blood samples will be collected to assess circulating hormones and metabolites. Stool samples will be collected to assess faecal microbiota composition. Subjective appetite measures will be collected using visual analogue scales. Breath hydrogen will be measured in real-time as a marker of intestinal fermentation. Finally, an in vitro continuous fermentation model will be inoculated with ileal fluid in order to understand the shift in microbial composition and SCFA produced in the colon following the different diets. Registration: ISRCTN11327221.