Imperial College London

ProfessorGaryFrost

Faculty of MedicineDepartment of Metabolism, Digestion and Reproduction

Chair in Nutrition and Dietetics
 
 
 
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Contact

 

+44 (0)20 7594 0959g.frost Website

 
 
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Location

 

Commonwealth BiuldingHammersmith HospitalHammersmith Campus

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Summary

 

Publications

Publication Type
Year
to

423 results found

Gressier M, Swinburn B, Frost G, Segal A, Sassi Fet al., 2020, What is the impact of food reformulation on individual’s behaviour, nutrient intakes and health status? A systematic review of empirical evidence, Obesity Reviews, ISSN: 1467-7881

Food reformulation aimed at improving the nutritional properties of food products has long been viewed as a promising public health strategy to tackle poor nutrition and obesity. This paper presents a review of the empirical evidence (i.e. modelling studies were excluded) on the impact of food reformulation on food choices, nutrient intakes and health status, based on a systematic search of Medline, Embase, Global Health, and sources of grey literature. Fifty-nine studies (in 35 papers) were included in the review. Most studies examined food choices (n=27) and dietary intakes (n=26). The nutrients most frequently studied were sodium (n=32) and trans-fatty acids (TFA, n=13). Reformulated products were generally accepted and purchased by consumers, which led to improved nutrient intakes in 73% of studies. We also conducted two meta-analyses showing, respectively, a -0.57g/day [95%CI -0.89, -0.25] reduction in salt intake, and an effect size for TFA intake reduction of -1.2, 95% [CI -1.79, -0.61]. Only six studies examined effects on health outcomes, with studies on TFA reformulation showing overall improvement in cardiovascular risk factors. For other nutrients, it remains unclear whether observed improvements in food choices or nutrient intakes may have led to an improvement in health outcomes.

Journal article

Caengprasath N, Gonzalez Abuin N, Shchepinova M, Inoue A, Ma Y, Tate E, Frost G, Hanyaloglu Aet al., 2020, Internalization-dependent free fatty acid receptor 2 signaling is essential for propionate- induced anorectic gut hormone release, iScience, Vol: 23, ISSN: 2589-0042

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.

Journal article

Mars RAT, Yang Y, Ward T, Houtti M, Priya S, Lekatz HR, Tang X, Sun Z, Kalari KR, Korem T, Bhattarai Y, Zheng T, Bar N, Frost G, Johnson AJ, van Treuren W, Han S, Ordog T, Grover M, Sonnenburg J, D'Amato M, Camilleri M, Elinav E, Segal E, Blekhman R, Farrugia G, Swann JR, Knights D, Kashyap PCet al., 2020, Longitudinal Multi-omics Reveals Subset-Specific Mechanisms Underlying Irritable Bowel Syndrome, Publisher: CELL PRESS, Pages: 1460-+, ISSN: 0092-8674

Conference paper

Beckmann M, Wilson T, Zubair H, Lloyd AJ, Lyons L, Phillips H, Tailliart K, Gregory N, Thatcher R, Garcia-Perez I, Frost G, Mathers JC, Draper Jet al., 2020, A standardized strategy for simultaneous quantification of urine metabolites to validate development of a biomarker panel allowing comprehensive assessment of dietary exposure., Molecular Nutrition and Food Research, Pages: e2000517-e2000517, ISSN: 1613-4125

SCOPE: Metabolites derived from individual foods found in human biofluids after consumption could provide objective measures of dietary intake. For comprehensive dietary assessment, quantification methods would need to manage the structurally diverse mixture of target metabolites present at a wide concentration range. METHODS & RESULTS: We developed a strategy for selection of candidate dietary exposure biomarkers, providing comprehensive coverage. An analytical method for 62 food biomarkers was validated by extensive analysis of chromatographic and ionization behaviour characteristics using triple quadrupole mass spectrometry. We used urine samples from two food intervention studies: one controlled, inpatient study (n = 19) and the other a free-living study where individuals (n = 15) were provided with food as a series of menu plans. As proof-of-principle, we demonstrated that the biomarker panel could discriminate between menu plans by detecting distinctive changes in the concentration in urine of targeted metabolites. We showed quantitative relationships between four biomarker concentrations in urine and dietary intake. CONCLUSIONS: We have demonstrated design concepts for an analytical strategy allowing simultaneous quantification of a comprehensive panel of chemically-diverse biomarkers of a wide range of commonly-consumed foods. We propose that integration of self-reported dietary recording tools with biomarker approaches will provide more robust assessment of dietary exposure. This article is protected by copyright. All rights reserved.

Journal article

Frampton J, Murphy KG, Frost G, Chambers ESet al., 2020, Short-chain fatty acids as potential regulators of skeletal muscle metabolism and function, Nature Metabolism, Vol: 2, Pages: 840-848, ISSN: 2522-5812

A key metabolic activity of the gut microbiota is the fermentation of non-digestible carbohydrate, which generates short-chain fatty acids (SCFAs) as the principal end products. SCFAs are absorbed from the gut lumen and modulate host metabolic responses at different organ sites. Evidence suggests that these organ sites include skeletal muscle, the largest organ in humans, which plays a pivotal role in whole-body energy metabolism. In this Review, we evaluate the evidence indicating that SCFAs mediate metabolic cross-talk between the gut microbiota and skeletal muscle. We discuss the effects of three primary SCFAs (acetate, propionate and butyrate) on lipid, carbohydrate and protein metabolism in skeletal muscle, and we consider the potential mechanisms involved. Furthermore, we highlight the emerging roles of these gut-derived metabolites in skeletal muscle function and exercise capacity, present limitations in current knowledge and provide suggestions for future work.

Journal article

Miras A, Kamocka A, Pérez-Pevida B, Purkayastha S, Moorthy K, Patel A, Chahal H, Frost G, Bassett P, Castagnetto-Gissey L, Coppin L, Jackson N, Umpleby M, Bloom S, Tan T, Ahmed A, Rubino Fet al., The effect of standard versus longer intestinal bypass on GLP-1 regulation and glucose metabolism in patients with type 2 diabetes undergoing roux-en-Y gastric bypass. The long-limb study, Diabetes Care, ISSN: 0149-5992

ObjectiveRoux-en-Y gastric bypass (RYGB) characteristically enhances post-prandial levels of Glucagon-like peptide 1 (GLP-1), a mechanism that contributes to its profound glucose-lowering effects. This enhancement is thought to be triggered by bypass of food to the distal small intestine with higher densities of neuroendocrine L-cells. We hypothesised that if this is the predominant mechanism behind the enhanced secretion of GLP-1, a longer intestinal bypass would potentiate the post-prandial peak in GLP-1, translating into higher insulin secretion and thus additional improvements in glucose tolerance. To investigate this, we conducted a mechanistic study comparing two variants of RYGB that differ in the length of intestinal bypass.Research Design and MethodsFifty-three patients with type 2 diabetes and obesity were randomised to either ‘standard limb’ RYGB (50cm biliopancreatic limb) or ‘long limb’ RYGB (150cm biliopancreatic limb). They underwent measurements of GLP-1 and insulin secretion following a mixed meal and insulin sensitivity using euglycaemic hyperinsulinaemic clamps at baseline, 2 weeks and at 20% weight loss after surgery.ResultsBoth groups exhibited enhancement in post-prandial GLP-1 secretion and improvements in glycaemia compared to baseline. There were no significant differences in post-prandial peak concentrations of GLP-1, time to peak, insulin secretion, and insulin sensitivity. ConclusionThe findings of this study demonstrate that lengthening of the intestinal bypass in RYGB does not affect GLP-1 secretion. Thus, the characteristic enhancement of GLP-1 response after RYGB might not depend on delivery of nutrients to more distal intestinal segments.

Journal article

Maitland K, Kiguli S, Olupot-Olupot P, Engoru C, Mellewa M, Goncalves PS, Opoka RO, Mpoya A, Alaroker F, Nteziyaremye J, Chagaluka G, Kennedy N, Nabawanuka E, Nakuya M, Namayanja C, Uyoga S, Byabazaire DK, Mbaya B, Wabwire B, Frost G, Bates I, Evans JA, Williams T, George EC, Gibb DM, Walker ASet al., 2020, Transfusion in African Children with Uncomplicated Severe Anemia, New England Journal of Medicine, ISSN: 0028-4793

Journal article

Garcia Perez I, Posma JM, Serrano Contreras JI, Boulange C, Chan Q, Frost G, Stamler J, Elliott P, Lindon J, Holmes E, Nicholson Jet al., 2020, Identifying unknown metabolites using NMR-based metabolic profiling techniques, Nature Protocols, Vol: 15, Pages: 2538-2567, ISSN: 1750-2799

Metabolic profiling of biological samples provides important insights into multiple physiological and pathological processes, but is hindered by a lack of automated annotation and standardised methods for structure elucidation of candidate disease biomarkers. Here, we describe a system for identifying molecular species derived from NMR spectroscopy based metabolic phenotyping studies, with detailed info on sample preparation, data acquisition, and data modelling. We provide eight different modular workflows to be followed in a recommended sequential order according to their level of difficulty. This multi-platform system involves the use of statistical spectroscopic tools such as STOCSY, STORM and RED-STORM to identify other signals in the NMR spectra relating to the same molecule. It also utilizes 2D-NMR spectroscopic analysis, separation and pre-concentration techniques, multiple hyphenated analytical platforms and data extraction from existing databases. The complete system, using all eight workflows, would take up to a month, as it includes multidimensional NMR experiments that require prolonged experiment times. However, easier identification cases using fewer steps would take two or three days. This approach to biomarker discovery is efficient, cost-effective and offers increased chemical space coverage of the metabolome, resulting in faster and more accurate assignment of NMR-generated biomarkers arising from metabolic phenotyping studies. Finally, it requires basic understanding of Matlab in order to perform statistical spectroscopic tools and analytical skills to perform Solid Phase Extraction, LC-fraction collection, LC-NMR-MS and 1D and 2D NMR experiments.

Journal article

Eriksen R, Garcia Perez I, Posma JM, Haid M, Sharma S, Prehn C, Thomas LE, Koivula RW, Bizzotto R, Prehn C, Mari A, Giordano GN, Pavo I, Schwenk JM, De Masi F, Tsirigos KD, Brunak S, Viñuela A, Mahajan A, McDonald TJ, Kokkola T, Rutter F, Teare H, Hansen TH, Fernandez J, Jones A, Jennison C, Walker M, McCarthy MI, Pedersen O, Ruetten H, Forgie I, Bell JD, Pearson ER, Franks PW, Adamski J, Holmes E, Frost Get al., 2020, Dietary metabolite profiling brings new insight into the relationship between nutrition and metabolic risk: An IMI DIRECT study, EBioMedicine, Vol: 58, Pages: 1-9, ISSN: 2352-3964

BackgroundDietary 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.MethodsWe 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.FindingsA 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), glu

Journal article

Farràs M, Martinez-Gili L, Portune K, Arranz S, Frost G, Tondo M, Blanco-Vaca Fet al., 2020, Modulation of the gut microbiota by olive oil phenolic compounds: implications for lipid metabolism, immune system, and obesity, Nutrients, Vol: 12, Pages: 1-28, ISSN: 2072-6643

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.

Journal article

Casanova-Marti A, Gonzalez-Abuin N, Serrano J, Blay MT, Terra X, Frost G, Pinent M, Ardevol Aet al., 2020, Long Term Exposure to a Grape Seed Proanthocyanidin Extract Enhances L-Cell Differentiation in Intestinal Organoids, MOLECULAR NUTRITION & FOOD RESEARCH, Vol: 64, ISSN: 1613-4125

Journal article

Gressier M, Frost G, Sassi F, 2020, Healthy foods and healthy diets. how government policies can steer food reformulation, Nutrients, Vol: 12, Pages: 1-9, ISSN: 2072-6643

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.

Journal article

Posma JM, Garcia Perez I, Frost G, Aljuraiban G, Chan Q, Van Horn L, Daviglus M, Stamler J, Holmes E, Elliott P, Nicholson Jet al., 2020, Nutriome-metabolome relationships provide insights into dietary intake and metabolism, Nature Food, Vol: 1, Pages: 426-436, ISSN: 2662-1355

Dietary assessment traditionally relies on self-reported data which are often inaccurate and may result in erroneous diet-disease risk associations. We illustrate how urinary metabolic phenotyping can be used as alternative approach for obtaining information on dietary patterns. We used two multi-pass 24-hr dietary recalls, obtained on two occasions on average three weeks apart, paired with two 24-hr urine collections from 1,848 U.S. individuals; 67 nutrients influenced the urinary metabotype measured with ¹H-NMR spectroscopy characterized by 46 structurally identified metabolites. We investigated the stability of each metabolite over time and showed that the urinary metabolic profile is more stable within individuals than reported dietary patterns. The 46 metabolites accurately predicted healthy and unhealthy dietary patterns in a free-living U.S. cohort and replicated in an independent U.K. cohort. We mapped these metabolites into a host-microbial metabolic network to identify key pathways and functions. These data can be used in future studies to evaluate how this set of diet-derived, stable, measurable bioanalytical markers are associated with disease risk. This knowledge may give new insights into biological pathways that characterize the shift from a healthy to unhealthy metabolic phenotype and hence give entry points for prevention and intervention strategies.

Journal article

Cherta-Murillo A, Lett AM, Frampton J, Chambers ES, Finnigan TJA, Frost GSet al., 2020, Effects of mycoprotein on glycaemic control and energy intake in humans: a systematic review, British Journal of Nutrition, Vol: 123, Pages: 1321-1332, ISSN: 0007-1145

Mycoprotein is a food high in both dietary fibre and non-animal derived protein. Global mycoprotein consumption is increasing although its effect on human health has not yet been systematically reviewed. This study aims to systematically review the effects of mycoprotein on glycaemic control and energy intake in humans. A literature search of randomised controlled trials was performed in Pubmed, EMBASE, Web of Science, Google Scholar and hand search. A total of 21 studies were identified of which only 5 studies, totalling 122 participants, met the inclusion criteria. All 5 studies were acute studies of which 1 reported outcomes on glycaemia and insulinaemia, 2 reported on energy intake and 2 reported on all of these outcomes. Data were extracted and risk-of-bias assessment was then conducted. The results did not show a clear effect of acute mycoprotein on blood glucose levels but it showed a decrease in insulin levels. Acute mycoprotein intake also showed to decrease energy intake at an <jats:italic>ad libitum</jats:italic> meal and post-24h in healthy lean, overweight and obese humans. In conclusion, the acute ingestion of mycoprotein reduces energy intake and insulinaemia whereas its impact on glycaemia is currently unclear. However, evidence comes from a very limited number of heterogeneous studies. Further well-controlled studies are needed to elucidate the short- and long-term effects of mycoprotein intake on glycaemic control and energy intake, as well as the mechanisms underpinning these effects.

Journal article

Garcia Perez I, Posma JM, Chambers E, Mathers J, Draper J, Beckmann M, Nicholson J, Holmes E, Frost Get al., 2020, Dietary metabotype modelling predicts individual responses to dietary interventions, Nature Food, Vol: 1, Pages: 355-364, ISSN: 2662-1355

Habitual consumption of poor quality diets is linked directly to risk factors for many non-communicable disease. This has resulted in the vast majority of countries globally and the World Health Organisation developing policies for healthy eating to reduce the prevalence of non communicable disease in the population. However, there is mounting evidence of variability in individual metabolic responses to any dietary intervention. We have developed a method for applying a pipeline for understanding inter-individual differences in response to diet, based on coupling data from highly-controlled dietary studies with deep metabolic phenotyping. In this feasibility study, we create an individual Dietary Metabotype Score (DMS) that embodies inter-individual variability in dietary response and captures consequent dynamic changes in concentrations of urinary metabolites. We find an inverse relationship between the DMS and blood glucose concentration. There is also a relationship between the DMS and urinary metabolic energy loss. Furthermore we employ a metabolic entropy approach to visualize individual and collective responses to dietary. Potentially, the DMS offers a method to target and to enhance dietary response at an individual level therefore reducing burden of non communicable diseases at a population level.

Journal article

Shchepinova MM, Hanyaloglu AC, Frost GS, Tate EWet al., 2020, Chemical biology of noncanonical G protein-coupled receptor signaling: Toward advanced therapeutics, CURRENT OPINION IN CHEMICAL BIOLOGY, Vol: 56, Pages: 98-110, ISSN: 1367-5931

Journal article

Atabaki-Pasdar N, Ohlsson M, Vinuela A, Frau F, Pomares-Millan H, Haid M, Jones AG, Thomas EL, Koivula RW, Kurbasic A, Mutie PM, Fitipaldi H, Fernandez J, Dawed AY, Giordano GN, Forgie IM, McDonald TJ, Rutters F, Cederberg H, Chabanova E, Dale M, Masi FD, Thomas CE, Allin KH, Hansen TH, Heggie A, Hong M-G, Elders PJM, Kennedy G, Kokkola T, Pedersen HK, Mahajan A, McEvoy D, Pattou F, Raverdy V, Haussler RS, Sharma S, Thomsen HS, Vangipurapu J, Vestergaard H, 't Hart LM, Adamski J, Musholt PB, Brage S, Brunak S, Dermitzakis E, Frost G, Hansen T, Laakso M, Pedersen O, Ridderstrale M, Ruetten H, Hattersley AT, Walker M, Beulens JWJ, Mari A, Schwenk JM, Gupta R, McCarthy MI, Pearson ER, Bell JD, Pavo I, Franks PWet al., 2020, Predicting and elucidating the etiology of fatty liver disease: A machine learning modeling and validation study in the IMI DIRECT cohorts, PLoS Medicine, Vol: 17, Pages: 1-27, ISSN: 1549-1277

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 (<5% or ≥5%) available for 1,514 participants. We applied LASSO (least absolute shrinkage and selection operator) to select features from the different layers of omics data and random forest analysis to develop the models. The prediction models included clinical and omics variables separately or in combination. A model including all omics and clinical variables yielded a cross-validated receiver operating characteristic area under the curve (ROCAUC) of 0.84 (95% CI 0.82, 0.86; p < 0.001), which compared with a ROCAUC of 0.82 (95% CI 0.81, 0.83; p < 0.001) for a model including 9 clinically accessible variables. The IMI DIRECT prediction models outperformed existing noninvasive NAFLD prediction tools. One limitation is that these analyses were performed in adults of European ancestry residing in northern Europe, and it is unknown how well these findings will translate to people of other ancestries and exposed to environmental risk factors that differ from those of the present cohort. Another key limitation of

Journal article

Dagbasi A, Lett A, Murphy K, Frost Get al., 2020, Understanding the interplay between food structure, intestinal bacterial fermentation and appetite control, Proceedings of the Nutrition Society, ISSN: 0029-6651

Epidemiological and clinical evidence highlight the benefit of dietary fibre consumption on body weight. This benefit is partly attributed to the interaction of dietary fibre with the gut microbiota. Dietary fibre possesses a complex food structure which resists digestion in the upper gut and therefore reaches the distal gut where it becomes available for bacterial fermentation. This process yields short chain fatty acids (SCFAs) which stimulate the release of appetite suppressing hormones Glucagon-like peptide-1 (GLP-1) and peptide YY (PYY). Food structures can further enhance the delivery of fermentable substrates to the distal gut by protecting the intracellular nutrients during upper gastro intestinal digestion. Domestic and industrial processing can disturb these food structures that act like barriers towards digestive enzymes. This leads to more digestible products that are better absorbed in the upper gut. As a result, less resistant material (fibre) and intracellular nutrients may reach the distal gut, thus reducing substrates for bacterial fermentation and its subsequent benefits on the host metabolism including appetite suppression. Understanding this link is essential for the design of diets and food products that can promote appetite suppression and act as a successful strategy towards obesity management. This article reviews the current evidence in the interplay between food structure, bacterial fermentation and appetite control.

Journal article

Malkova D, Polyviou T, Rizou E, Gerasimidis K, Chambers ES, Preston T, Tedford MC, Frost G, Morrison DJet al., 2020, Moderate intensity exercise training combined with inulin-propionate ester supplementation increases whole body resting fat oxidation in overweight women, Metabolism: clinical and experimental, Vol: 104, ISSN: 0026-0495

BACKGROUND: Our previous work has shown that oral supplementation with inulin propionate ester (IPE) reduces intra-abdominal fat and prevents weight gain and that oral propionate intake enhances resting fat oxidation. The effects of IPE combined with exercise training on energy substrate utilisation are unknown. The aim of this study was to investigate the impact of 4-weeks IPE supplementation, in combination with a moderate intensity exercise training programme, on whole body fat oxidation and on plasma GLP-1 and PYY. METHODS: Twenty overweight healthy women participated in randomised parallel study and underwent 4 weeks of supervised exercise training either with IPE (EX/IPE group) or Placebo (EX/Placebo group) supplementation. Before and after the intervention participants conducted an experimental trial, which involved collection of expired gas and blood samples in the fasted state and during 7 h of the postprandial state. RESULTS: Within groups, the EX/IPE group significantly enhanced the amount of fat (Pre, 24.1 ± 1.2 g; Post, 35.9 ± 4.0 g, P < 0.05) oxidised and reduced CHO (Pre, 77.8 ± 6.0 g; Post, 57.8 ± 7.7 g, P < 0.05) oxidised, reduced body weight (Pre, 77.3 ± 4.2 kg; Post, 76.6 ± 4.1 kg, P < 0.05) and body fat mass (Pre, 37.7 ± 1.9%; Post, 36.9 ± 1.9%, P < 0.05). In EX/Placebo group, changes in amount of fat (Pre, 36.8 ± 3.9 g; Post, 37.0 ± 4.0 g) and CHO (Pre, 62.7 ± 6.5 g; Post, 61.5 ± 7.4 g) oxidised, body weight (Pre, 84.2 ± 4.3 kg; Post, 83.6 ± 4.3 kg) and body fat mass (Pre, 40.1 ± 1.9%; Post, 38.7 ± 1.5%) were not significant (P > 0.05). Comparing between groups, changes in the amount of fat oxidised were significantly (P < 0.05) different and a trend for difference was observed for amount of CHO oxidised (P = 0.06) and RER (P = 0.06). The interventions had no impact on fasting or postprandial plasma concentrations of

Journal article

Jobarteh ML, McCrory MA, Lo B, Sun M, Sazonov E, Anderson AK, Jia W, Maitland K, Qiu J, Steiner-Asiedu M, Higgins JA, Baranowski T, Olupot-Olupot P, Frost Get al., 2020, Development and validation of objective, passive dietary assessment Method for estimating food and nutrient intake in households in Low and Middle-Income Countries (LMICs): a study protocol, Current Developments in Nutrition, Vol: 4, Pages: 1-11, ISSN: 2475-2991

Malnutrition is a major concern in low- and middle-income countries (LMIC), but the full extent of nutritional deficiencies remains unknown largely due to lack of accurate assessment methods. This study seeks to develop and validate an objective, passive method of estimating food and nutrient intake in households in Ghana and Uganda. Household members (including under-5s and adolescents) are assigned a wearable camera device to capture images of their food intake during waking hours. Using custom software, images captured are then used to estimate an individual's food and nutrient (i.e., protein, fat, carbohydrate, energy, and micronutrients) intake. Passive food image capture and assessment provides an objective measure of food and nutrient intake in real time, minimizing some of the limitations associated with self-reported dietary intake methods. Its use in LMIC could potentially increase the understanding of a population's nutritional status, and the contribution of household food intake to the malnutrition burden. This project is registered at clinicaltrials.gov (NCT03723460).

Journal article

Koivula RW, Atabaki-Pasdar N, Giordano GN, White T, Adamski J, Bell JD, Beulens J, Brage S, Brunak S, De Masi F, Dermitzakis ET, Forgie IM, Frost G, Hansen T, Hansen TH, Hattersley A, Kokkola T, Kurbasic A, Laakso M, Mari A, McDonald TJ, Pedersen O, Rutters F, Schwenk JM, Teare HJA, Thomas EL, Vinuela A, Mahajan A, McCarthy MI, Ruetten H, Walker M, Pearson E, Pavo I, Franks PWet al., 2020, The role of physical activity in metabolic homeostasis before and after the onset of type 2 diabetes: an IMI DIRECT study, Diabetologia, Vol: 63, Pages: 744-756, ISSN: 0012-186X

Aims/hypothesisIt is well established that physical activity, abdominal ectopic fat and glycaemic regulation are related but the underlying structure of these relationships is unclear. The previously proposed twin-cycle hypothesis (TC) provides a mechanistic basis for impairment in glycaemic control through the interactions of substrate availability, substrate metabolism and abdominal ectopic fat accumulation. Here, we hypothesise that the effect of physical activity in glucose regulation is mediated by the twin-cycle. We aimed to examine this notion in the Innovative Medicines Initiative Diabetes Research on Patient Stratification (IMI DIRECT) Consortium cohorts comprised of participants with normal or impaired glucose regulation (cohort 1: N ≤ 920) or with recently diagnosed type 2 diabetes (cohort 2: N ≤ 435).MethodsWe defined a structural equation model that describes the TC and fitted this within the IMI DIRECT dataset. A second model, twin-cycle plus physical activity (TC-PA), to assess the extent to which the effects of physical activity in glycaemic regulation are mediated by components in the twin-cycle, was also fitted. Beta cell function, insulin sensitivity and glycaemic control were modelled from frequently sampled 75 g OGTTs (fsOGTTs) and mixed-meal tolerance tests (MMTTs) in participants without and with diabetes, respectively. Abdominal fat distribution was assessed using MRI, and physical activity through wrist-worn triaxial accelerometry. Results are presented as standardised beta coefficients, SE and p values, respectively.ResultsThe TC and TC-PA models showed better fit than null models (TC: χ2 = 242, p = 0.004 and χ2 = 63, p = 0.001 in cohort 1 and 2, respectively; TC-PA: χ2 = 180, p = 0.041 and χ2 = 60, p = 0.008 in cohort 1 and 2, respectively). The association of physical activity wi

Journal article

Brown A, Dornhorst A, McGowan B, Omar O, Leeds AR, Taheri S, Frost Get al., 2020, A low energy total diet replacement intervention in patients with type 2 diabetes mellitus and obesity treated with insulin – a randomized trial, BMJ Open Diabetes Research and Care, Vol: 8, ISSN: 2052-4897

Objectives The management of patients with long-standing type 2 diabetes and obesity receiving insulin therapy (IT) is a substantial clinical challenge. Our objective was to examine the effect of a low-energy total diet replacement (TDR) intervention versus standardized dietetic care in patients with long-standing type 2 diabetes and obesity receiving IT.Research design and methods In a prospective randomized controlled trial, 90 participants with type 2 diabetes and obesity receiving IT were assigned to either a low-energy TDR (intervention) or standardized dietetic care (control) in an outpatient setting. The primary outcome was weight loss at 12 months with secondary outcomes including glycemic control, insulin burden and quality of life (QoL).Results Mean weight loss at 12 months was 9.8 kg (SD 4.9) in the intervention and 5.6 kg (SD 6.1) in the control group (adjusted mean difference −4.3 kg, 95% CI −6.3 to 2.3, p<0.001). IT was discontinued in 39.4% of the intervention group compared with 5.6% of the control group among completers. Insulin requirements fell by 47.3 units (SD 36.4) in the intervention compared with 33.3 units (SD 52.9) in the control (−18.6 units, 95% CI −29.2 to –7.9, p=0.001). Glycated Hemoglobin (HbA1c) fell significantly in the intervention group (4.7 mmol/mol; p=0.02). QoL improved in the intervention group of 11.1 points (SD 21.8) compared with 0.71 points (SD 19.4) in the control (8.6 points, 95% CI 2.0 to 15.2, p=0.01).Conclusions Patients with advanced type 2 diabetes and obesity receiving IT achieved greater weight loss using a TDR intervention while also reducing or stopping IT and improving glycemic control and QoL. The TDR approach is a safe treatment option in this challenging patient group but requires maintenance support for long-term success.

Journal article

Yin X, Gibbons H, Rundle M, Frost G, McNulty BA, Nugent AP, Walton J, Flynn A, Brennan Let al., 2020, The Relationship between Fish Intake and Urinary Trimethylamine-N-Oxide, MOLECULAR NUTRITION & FOOD RESEARCH, Vol: 64, ISSN: 1613-4125

Journal article

Johns I, Frost G, Dornhorst A, 2020, Increasing the proportion of plasma MUFA, as a result of dietary intervention, is associated with a modest improvement in insulin sensitivity, JOURNAL OF NUTRITIONAL SCIENCE, Vol: 9, ISSN: 2048-6790

Journal article

Corrado M, Cherta-Murillo A, Chambers ES, Wood AJ, Plummer A, Lovegrove A, Edwards CH, Frost GS, Hazard BAet al., 2020, Effect of semolina pudding prepared from starch branching enzyme IIa and b mutant wheat on glycaemic response in vitro and in vivo: a randomised controlled pilot study, FOOD & FUNCTION, Vol: 11, Pages: 617-627, ISSN: 2042-6496

Journal article

Cade J, Wark P, Frost G, Alwan N, Carter M, Elliott P, Ford H, Hancock N, Morris M, Mulla Z, Noorwali E, Petropoulou A, Potter G, Riboli E, Hardie L, Greenwood Det al., 2020, Validation of an automated online 24-hour recall (myfood24) using nutrient biomarkers provides similar results to a traditional interviewer administered recall, Publisher: CAMBRIDGE UNIV PRESS, Pages: E391-E391, ISSN: 0029-6651

Conference paper

Blaak EE, Canfora EE, Theis S, Frost G, Groen AK, Mithieux G, Nauta A, Scott K, Stahl B, van Harsselaar J, van Tol R, Vaughan EE, Verbeke Ket al., 2020, Short chain fatty acids in human gut and metabolic health, BENEFICIAL MICROBES, Vol: 11, Pages: 411-455, ISSN: 1876-2883

Journal article

Gressier M, Segal A, Sassi F, Frost Get al., 2020, The effect of single-nutrient reformulation initiatives on the nutrient profile of foods: a systematic review, Publisher: CAMBRIDGE UNIV PRESS, Pages: E565-E565, ISSN: 0029-6651

Conference paper

Wandrag L, Brett SJ, Frost GS, Bountziouka V, Hickson Met al., 2019, Exploration of muscle loss and metabolic state during prolonged critical illness: Implications for intervention?, PLOS ONE, Vol: 14, ISSN: 1932-6203

Journal article

Wilson T, Garcia-Perez I, Posma JM, Lloyd AJ, Chambers ES, Tailliart K, Zubair H, Beckmann M, Mathers JC, Holmes E, Frost G, Draper Jet al., 2019, Spot and cumulative urine samples are suitable replacements for 24-hour urine collections for objective measures of dietary exposure in adults using metabolite biomarkers, Journal of Nutrition, Vol: 149, Pages: 1692-1700, ISSN: 0022-3166

BACKGROUND: Measurement of multiple food intake exposure biomarkers in urine may offer an objective method for monitoring diet. The potential of spot and cumulative urine samples that have reduced burden on participants as replacements for 24-h urine collections has not been evaluated. OBJECTIVE: The aim of this study was to determine the utility of spot and cumulative urine samples for classifying the metabolic profiles of people according to dietary intake when compared with 24-h urine collections in a controlled dietary intervention study. METHODS: Nineteen healthy individuals (10 male, 9 female, aged 21-65 y, BMI 20-35 kg/m2) each consumed 4 distinctly different diets, each for 1 wk. Spot urine samples were collected ∼2 h post meals on 3 intervention days/wk. Cumulative urine samples were collected daily over 3 separate temporal periods. A 24-h urine collection was created by combining the 3 cumulative urine samples. Urine samples were analyzed with metabolite fingerprinting by both high-resolution flow infusion electrospray mass spectrometry (FIE-HRMS) and proton nuclear magnetic resonance spectroscopy (1H-NMR). Concentrations of dietary intake biomarkers were measured with liquid chromatography triple quadrupole mass spectrometry and by integration of 1H-NMR data. RESULTS: Cross-validation modeling with 1H-NMR and FIE-HRMS data demonstrated the power of spot and cumulative urine samples in predicting dietary patterns in 24-h urine collections. Particularly, there was no significant loss of information when post-dinner (PD) spot or overnight cumulative samples were substituted for 24-h urine collections (classification accuracies of 0.891 and 0.938, respectively). Quantitative analysis of urine samples also demonstrated the relation between PD spot samples and 24-h urines for dietary exposure biomarkers. CONCLUSIONS: We conclude that PD spot urine samples are suitable replacements for 24-h urine collections. Alternatively, cumulative samples collected overn

Journal article

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