Imperial College London

DrEdwardChambers

Faculty of MedicineDepartment of Metabolism, Digestion and Reproduction

Non-Clinical Lecturer
 
 
 
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e.chambers

 
 
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10.N4Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

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69 results found

Chambers E, Frampton J, Serrano-Contreras JI, Garcia-Perez I, Franco-Becker G, Penhaligan J, Tan A, Cepas de Oliveira AC, Milner A, Murphy K, Frost Get al., 2024, The impact of acute exercise on appetite regulation: Unravelling the potential involvement of gut microbial activity, The Journal of Physiology, Vol: 602, Pages: 529-530, ISSN: 0022-3751

Journal article

Frampton J, Serrano Contreras J, Garcia Perez I, Franco Becker G, Penhaligan J, Tan A, Cepas de Oliveira AC, Milner A, Murphy K, Frost G, Chambers Eet al., 2023, The metabolic interplay between dietary carbohydrate and exercise and its role in acute appetite-regulation in males: a randomised controlled study, The Journal of Physiology, Vol: 601, Pages: 3461-3480, ISSN: 0022-3751

An understanding of the metabolic determinants of postexercise appetite regulation would facilitate development of adjunctive therapeutics to suppress compensatory eating behaviours and improve the efficacy of exercise as a weight-loss treatment. Metabolic responses to acute exercise are, however, dependent on pre-exercise nutritional practices, including carbohydrate intake. We therefore aimed to determine the interactive effects of dietary carbohydrate and exercise on plasma hormonal and metabolite responses and explore mediators of exercise-induced changes in appetite regulation across nutritional states. In this randomized crossover study, participants completed four 120 min visits: (i) control (water) followed by rest; (ii) control followed by exercise (30 min at ∼75% of maximal oxygen uptake); (iii) carbohydrate (75 g maltodextrin) followed by rest; and (iv) carbohydrate followed by exercise. An ad libitum meal was provided at the end of each 120 min visit, with blood sample collection and appetite assessment performed at predefined intervals. We found that dietary carbohydrate and exercise exerted independent effects on the hormones glucagon-like peptide 1 (carbohydrate, 16.8 pmol/L; exercise, 7.4 pmol/L), ghrelin (carbohydrate, −48.8 pmol/L; exercise: −22.7 pmol/L) and glucagon (carbohydrate, 9.8 ng/L; exercise, 8.2 ng/L) that were linked to the generation of distinct plasma 1H nuclear magnetic resonance metabolic phenotypes. These metabolic responses were associated with changes in appetite and energy intake, and plasma acetate and succinate were subsequently identified as potential novel mediators of exercise-induced appetite and energy intake responses. In summary, dietary carbohydrate and exercise independently influence gastrointestinal hormones associated with appetite regulation. Future work is warranted to probe the mechanistic importance of plasma acetate and succinate in postexercise appetite regulation.

Journal article

Cherta-Murillo A, Danckert NP, Valdivia-Garcia M, Chambers ES, Roberts L, Miguens-Blanco J, McDonald JAK, Marchesi JR, Frost GSet al., 2023, Gut microbiota fermentation profiles of pre-digested mycoprotein (Quorn) using faecal batch cultures <i>in vitro</i>: a preliminary study, INTERNATIONAL JOURNAL OF FOOD SCIENCES AND NUTRITION, Vol: 74, Pages: 327-337, ISSN: 0963-7486

Journal article

Garcia-Perez I, Posma JM, Chambers ES, Mathers JC, Draper J, Beckmann M, Nicholson JK, Holmes E, Frost Get al., 2023, Dietary metabotype modelling predicts individual responses to dietary interventions (Vol 1, pg 355, 2020) (Retraction of Vol 1, Pg 355, 2020), NATURE FOOD, Vol: 4, Pages: 269-269

Journal article

Lu H, George J, Eslam M, Villanueva A, Bolondi L, Reeves HL, McCain M, Chambers E, Ward C, Sartika D, Sands C, Maslen L, Lewis MR, Ramaswami R, Sharma Ret al., 2023, Discriminatory changes in circulating metabolites as a predictor of hepatocellular cancer in patients with MAFLD, Liver Cancer, Vol: 12, Pages: 19-31, ISSN: 2235-1795

Introduction: The burden of metabolic (dysfunction) associated fatty liver disease (MAFLD) is rising mirrored by an increase in hepatocellular cancer (HCC). MAFLD and its sequelae are characterized by perturbations in lipid handling, inflammation, and mitochondrial damage. The profile of circulating lipid and small molecule metabolites with the development of HCC is poorly characterized in MAFLD and could be used in future studies as a biomarker for HCC. Methods: We assessed the profile of 273 lipid and small molecule metabolites by ultra-performance liquid chromatography coupled to high-resolution mass spectrometry in serum from patients with MAFLD (n = 113) and MAFLD-associated HCC (n = 144) from six different centers. Regression models were used to identify a predictive model of HCC. Results: Twenty lipid species and one metabolite, reflecting changes in mitochondrial function and sphingolipid metabolism, were associated with the presence of cancer on a background of MAFLD with high accuracy (AUC 0.789, 95% CI: 0.721–0.858), which was enhanced with the addition of cirrhosis to the model (AUC 0.855, 95% CI: 0.793–0.917). In particular, the presence of these metabolites was associated with cirrhosis in the MAFLD subgroup (p < 0.001). When considering the HCC cohort alone, the metabolic signature was an independent predictor of overall survival (HR 1.42, 95% CI: 1.09–1.83, p < 0.01). Conclusion: These exploratory findings reveal a metabolic signature in serum which is capable of accurately detecting the presence of HCC on a background of MAFLD. This unique serum signature will be taken forward for further investigation of diagnostic performance as biomarker of early stage HCC in patients with MAFLD in the future.

Journal article

Chew W, Lim YP, Lim WS, Chambers ES, Frost G, Wong SH, Ali Yet al., 2023, Gut-muscle crosstalk. A perspective on influence of microbes on muscle function, FRONTIERS IN MEDICINE, Vol: 9

Journal article

Cai M, Edwards C, Tashkova M, Tejpal S, Blunt D, Garcia Perez I, Serrano Contreras J, Chambers E, Frost Get al., 2023, Cell wall matrices in chickpeas and their effects on starch digestion and postprandial metabolism, Winter Conference 2022/23,Architecture of food: processing, structure and health, Publisher: Cambridge University Press, ISSN: 0029-6651

Conference paper

Brignardello J, Fountana S, Posma JM, Chambers ES, Nicholson JK, Wist J, Frost G, Garcia-Perez I, Holmes Eet al., 2022, Characterization of diet-dependent temporal changes in circulating short-chain fatty acid concentrations: a randomized crossover dietary trial, The American Journal of Clinical Nutrition, Vol: 116, Pages: 1368-1378, ISSN: 0002-9165

Background: Production of Short-chain fatty acids (SCFAs) from food is a complex and dynamic saccharolytic fermentation process mediated by both human and gut microbial factors. SCFA production and knowledge of the relationship between SCFA profiles and dietary patterns is lacking. Objective: Temporal changes in SCFA levels in response to two contrasting diets were investigated using a novel GC-MS method.Design: Samples were obtained from a randomized, controlled, crossover trial designed to characterize the metabolic response to four diets. Participants (n=19) undertook these diets during an inpatient stay (of 72-h). Serum samples were collected 2-h after breakfast (AB), lunch (AL) and dinner (AD) on day 3 and a fasting sample (FA) was obtained on day 4. 24-h urine samples were collected on day 3. In this sub-study, samples from the two extreme diets representing a diet with high adherence to WHO healthy eating recommendations and a typical Western diet were analyzed using a bespoke GC-MS method developed to detect and quantify 10 SCFAs and precursors in serum and urine samples. Results: Considerable inter-individual variation in serum SCFA concentrations was observed across all time points and temporal fluctuations were observed for both diets. Although the sample collection timing exerted a greater magnitude of effect on circulating SCFA concentrations, the unhealthy diet was associated with a lower concentration of acetic acid (FA: coefficient=-17.0; standard error (SE)=5.8; p-trend=0.00615), 2-methylbutyric acid (AL: coefficient=-0.1; SE=0.028; p-trend=4.13x10-4 and AD: coefficient =-0.1; SE:=0.028; p-trend=2.28x10-3) and 2-hydroxybutyric acid (FA: coefficient=-15.8; standard error=5.11; p-trend: 4.09x10-3). In contrast lactic acid was significantly higher in the unhealthy diet (AL: coefficient=750.2; standard error=315.2; p-trend=0.024 and AD: coefficient=1219.3; standard error=322.6; p-trend: 8.28x10-4). Conclusion: The GC-MS method allowed robust mapping of

Journal article

Frampton J, Izzi-Engbeaya C, Salem V, Murphy KG, Tan TM, Chambers ESet al., 2022, The acute effect of glucagon on components of energy balance and glucose homoeostasis in adults without diabetes: a systematic review and meta-analysis, International Journal of Obesity, Vol: 46, Pages: 1948-1959, ISSN: 0307-0565

ObjectiveUsing a systematic review and meta-analysis, we aimed to estimate the mean effect of acute glucagon administration on components of energy balance and glucose homoeostasis in adults without diabetes.MethodsCENTRAL, CINAHL, Embase, MEDLINE, PubMed, and Scopus databases were searched from inception to May 2021. To be included, papers had to be a randomised, crossover, single- or double-blind study, measuring ad libitum meal energy intake, energy expenditure, subjective appetite, glucose, and/or insulin following acute administration of glucagon and an appropriate comparator in adults without diabetes. Risk of bias was assessed using the Revised Cochrane Risk of Bias Tool for Randomized trials with additional considerations for cross-over trials. Certainty of evidence was assessed using the GRADE approach. Random-effect meta-analyses were performed for outcomes with at least five studies. This study is registered on PROSPERO (CRD42021269623).ResultsIn total, 13 papers (15 studies) were considered eligible: energy intake (5 studies, 77 participants); energy expenditure (5 studies, 59 participants); subjective appetite (3 studies, 39 participants); glucose (13 studies, 159 participants); insulin (12 studies, 147 participants). All studies had some concerns with regards to risk of bias. Mean intervention effect of acute glucagon administration on energy intake was small (standardised mean difference [SMD]: –0.19; 95% CI, –0.59 to 0.21; P = 0.345). Mean intervention effect of acute glucagon administration on energy expenditure (SMD: 0.72; 95% CI, 0.37–1.08; P < 0.001), glucose (SMD: 1.11; 95% CI, 0.60–1.62; P < 0.001), and insulin (SMD: 1.33; 95% CI, 0.88–1.77; P < 0.001) was moderate to large.ConclusionsAcute glucagon administration produces substantial increases in energy expenditure, and in circulating insulin and glucose concentrations. However, the effect of acute g

Journal article

Cherta-Murillo A, Pugh JE, Alaraj-Alshehhi S, Hajjar D, Frost G, Chambers Eet al., 2022, The effect of short-chain fatty acids on glycemic control in humans: A systematic review and meta-analysis, American Journal of Clinical Nutrition, Vol: 116, ISSN: 0002-9165

Background:Non-communicable disease development is related to impairments in glycaemic and insulinemic response, which can be modulated by fiber intake. Fiber's beneficial effect upon metabolic health can be partially attributed to the production of short-chain fatty acids (SCFAs) via microbial fermentation of fiber in the gastrointestinal tract.Objective:We aimed to determine the effect of the SCFAs, acetate, propionate, and butyrate on glycemic control in humans.Methods:CENTRAL, Embase, PubMed, Scopus and Web of Science databases were searched from inception to the 07/12/2021. Papers were included if they reported a randomized, controlled trial measuring glucose and/or insulin compared to a placebo in adults. Studies were categorized by the type of SCFA and intervention duration. Random effects meta-analyses were performed for glucose and insulin for those subject categories with ≥3 studies, or a narrative review was performed.Results:We identified 43 eligible papers, with 46 studies within those records (n = 913), 44 studies were included in the meta-analysis. Vinegar intake decreased acute glucose response, standard mean difference (SMD) and (95% CI) –0.53 (–0.92, –0.14) (n = 67) in individuals with impaired glucose tolerance or type 2 diabetes and in healthy (SMD) –0.27 (–0.54, 0.00) (n = 186). The meta-analyses for acute acetate as well as acute and chronic propionate studies had no significant effect.Conclusions:Vinegar decreased glucose response acutely in healthy and non-healthy. Acetate, propionate, butyrate, and mixed SCFAs had no effect on blood glucose and insulin in humans. Significant heterogeneity, risk of bias, and publication bias were identified in several study categories, including acute vinegar glucose response. As evidence was very uncertain, caution is urged when interpreting these results. Further high-quality research is required to determine the effect of SCFAs on glycemic control.

Journal article

Frampton J, Murphy K, Frost G, Chambers Eet al., 2021, Higher dietary fibre intake is associated with increased skeletal muscle mass and strength in adults aged 40 years and older, Journal of Cachexia, Sarcopenia and Muscle, Vol: 12, Pages: 2134-2144, ISSN: 2190-6009

BackgroundSkeletal muscle mass begins to decline from 40 years of age. Limited data suggest that dietary fibre may modify lean body mass, 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. MethodsWe 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 body mass components (body mass, 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). Body mass components and skeletal muscle strength were expressed relative to body mass (per kg of body mass [BM]). ResultsHigher intakes of dietary fibre were significantly associated with increased relative total lean mass (β: 0.69 g/kg BM; 95% CI, 0.48 to 0.89 g/kg BM; P<0.001), relative appendicular lean mass (β: 0.34 g/kg BM; 95% CI, 0.23 to 0.45 g/kg BM; P<0.001), relative bone mineral content (β: 0.05 g/kg BM; 95% CI, 0.02 to 0.07 g/kg BM; P<0.001), and relative combined grip strength (β: 0.002 kg/kg BM; 95% CI, 0.001 to 0.003 kg/kg BM; P<0.001).Conversely, higher dietary fibre intakes were significantly associated with a lower body mass (β: -0.20; 95% CI, -0.28 to -0.11 kg; P<0.001), BMI (β: -0.08 kg/m2; 95%CI, -0.10 to -0.05 kg/m2), relative total fat (β: -0.68 g/kg BM; 95% CI, -0.89 to -0.47 g/kg BM; P<0.001), relative trunk fat (β: -0.48 g/kg BM; 95%CI, -0.63 to -0.33 g/kg; P<0.001), fasting glucose (β: -0.01 mmol/L; 95% CI, -0.02 to -0.00 mmol/L; P=0.017), fasting ins

Journal article

Frampton J, Edinburgh R, Ogden H, Gonzalez J, Chambers Eet al., 2021, The acute effect of fasted exercise on energy intake, energy expenditure, subjective hunger and gastrointestinal hormone release compared to fed exercise in healthy individuals: A systematic review and network meta-analysis, International Journal of Obesity, Vol: 46, Pages: 255-268, ISSN: 0307-0565

ObjectiveTo determine the acute effect of fasted and fed exercise on energy intake, energy expenditure, subjective hunger and gastrointestinal hormone release.MethodsCENTRAL, Embase, MEDLINE, PsycInfo, PubMed, Scopus and Web of Science databases were searched to identify randomised, crossover studies in healthy individuals that compared the following interventions: (i) fasted exercise with a standardised post-exercise meal [FastEx + Meal], (ii) fasted exercise without a standardised post-exercise meal [FastEx + NoMeal], (iii) fed exercise with a standardised post-exercise meal [FedEx + Meal], (iv) fed exercise without a standardised post-exercise meal [FedEx + NoMeal]. Studies must have measured ad libitum meal energy intake, within-lab energy intake, 24-h energy intake, energy expenditure, subjective hunger, acyl-ghrelin, peptide YY, and/or glucagon-like peptide 1. Random-effect network meta-analyses were performed for outcomes containing ≥5 studies.Results17 published articles (23 studies) were identified. Ad libitum meal energy intake was significantly lower during FedEx + Meal compared to FedEx + NoMeal (MD: −489 kJ; 95% CI, −898 to −80 kJ; P = 0.019). Within-lab energy intake was significantly lower during FastEx + NoMeal compared to FedEx + NoMeal (MD: −1326 kJ; 95% CI, −2102 to −550 kJ; P = 0.001). Similarly, 24-h energy intake following FastEx + NoMeal was significantly lower than FedEx + NoMeal (MD: −2095 kJ; 95% CI, −3910 kJ to −280 kJ; P = 0.024). Energy expenditure was however significantly lower during FastEx + NoMeal compared to FedEx+NoMeal (MD: −0.67 kJ/min; 95% CI, −1.10 to −0.23 kJ/min; P = 0.003). Subjective hunger was significantly

Journal article

Wu Y, Posma JM, Holmes E, Chambers E, Frost G, Garcia Perez Iet al., 2021, Odd chain fatty acids are not robust biomarkers for dietary intake of fiber, Molecular Nutrition and Food Research, Vol: 65, Pages: 1-8, ISSN: 1613-4125

Prior investigation has suggested a positive association between increased colonic propionate production and circulating odd-chain fatty acids [(OCFAs; pentadecanoic acid (C15:0), heptadecanoic acid (C17:0)]. As the major source of propionate in humans is the microbial fermentation of dietary fiber, OCFAs have been proposed as candidate biomarkers of dietary fiber. The objective of this study is to critically assess the plausibility, robustness, reliability, dose-response, time-response aspects of OCFAs as potential biomarkers of fermentable fibers in two independent studies using a validated analytical method. OCFAs were first assessed in a fiber supplementation study, where 21 participants received 10g dietary fiber supplementation for 7 days with blood samples collected on the final day at a 420 minute study visit. OCFAs were then assessed in a highly controlled inpatient setting, which 19 participants consumed a high fiber (45.1g/day) and a low fiber diet (13.6g/day) for 4 days. Collectively in both studies, dietary intakes of fiber as fiber supplementations or having consumed a high fiber diet did not increase circulating levels of OCFAs. The dose and temporal relations were not observed. Current study has generated new insight on the utility of OCFAs as fiber biomarkers and highlighted the importance of critical assessment of candidate dietary biomarkers before application.

Journal article

Prokopidis K, Chambers E, Ni Lochlainn M, Witard OCet al., 2021, Mechanisms Linking the Gut-Muscle Axis With Muscle Protein Metabolism and Anabolic Resistance: Implications for Older Adults at Risk of Sarcopenia, Frontiers in Physiology, Vol: 12

Aging is associated with a decline in skeletal muscle mass and function—termed sarcopenia—as mediated, in part, by muscle anabolic resistance. This metabolic phenomenon describes the impaired response of muscle protein synthesis (MPS) to the provision of dietary amino acids and practice of resistance-based exercise. Recent observations highlight the gut-muscle axis as a physiological target for combatting anabolic resistance and reducing risk of sarcopenia. Experimental studies, primarily conducted in animal models of aging, suggest a mechanistic link between the gut microbiota and muscle atrophy, mediated via the modulation of systemic amino acid availability and low-grade inflammation that are both physiological factors known to underpin anabolic resistance. Moreover, in vivo and in vitro studies demonstrate the action of specific gut bacteria (Lactobacillus and Bifidobacterium) to increase systemic amino acid availability and elicit an anti-inflammatory response in the intestinal lumen. Prospective lifestyle approaches that target the gut-muscle axis have recently been examined in the context of mitigating sarcopenia risk. These approaches include increasing dietary fiber intake that promotes the growth and development of gut bacteria, thus enhancing the production of short-chain fatty acids (SCFA) (acetate, propionate, and butyrate). Prebiotic/probiotic/symbiotic supplementation also generates SCFA and may mitigate low-grade inflammation in older adults via modulation of the gut microbiota. Preliminary evidence also highlights the role of exercise in increasing the production of SCFA. Accordingly, lifestyle approaches that combine diets rich in fiber and probiotic supplementation with exercise training may serve to produce SCFA and increase microbial diversity, and thus may target the gut-muscle axis in mitigating anabolic resistance in older adults. Future mechanistic studies are warranted to establish the direct physiological action of distinct gut

Journal article

Frampton J, Cobbold B, Nozdrin M, Oo HTH, Wilson H, Murphy KG, Frost G, Chambers ESet al., 2021, The effect of a single bout of continuous aerobic exercise on glucose, insulin and glucagon concentrations compared to resting conditions in healthy adults: a systematic review, meta-analysis and meta-regression, Sports Medicine, Vol: 51, Pages: 1949-1966, ISSN: 0112-1642

Background:Elevated glucose and insulin levels are major risk factors in the development of cardiometabolic disease. Aerobic exercise is widely recommended to improve glycaemic control, yet its acute effect on glycaemia and glucoregulatory hormones has not been systematically reviewed and analysed in healthy adults.Objective:To determine the effect of a single bout of continuous aerobic exercise on circulating glucose, insulin, and glucagon concentrations in healthy adults.Methods:CENTRAL, CINAHL, Embase, Global Health, HMIC, Medline, PubMed, PsycINFO, ScienceDirect, Scopus and Web of Science databases were searched from inception to May 2020. Papers were included if they reported a randomised, crossover study measuring glucose and/or insulin and/or glucagon concentrations before and immediately after a single bout of continuous aerobic exercise (≥ 30 min) compared to a time-matched, resting control arm in healthy adults. The risk of bias and quality of evidence were assessed using the Cochrane Risk of Bias Tool and GRADE approach, respectively. Random-effects meta-analyses were performed for glucose, insulin, and glucagon. Sub-group meta-analyses and meta-regression were performed for categorical (metabolic state [postprandial or fasted], exercise mode [cycle ergometer or treadmill]) and continuous (age, body mass index, % males, maximal aerobic capacity, exercise duration, exercise intensity) covariates, respectively.Results42 papers (51 studies) were considered eligible: glucose (45 studies, 391 participants), insulin (38 studies, 377 participants) and glucagon (5 studies, 47 participants). Acute aerobic exercise had no significant effect on glucose concentrations (mean difference: − 0.05 mmol/L; 95% CI, − 0.22 to 0.13 mmol/L; P = 0.589; I2: 91.08%, large heterogeneity; moderate-quality evidence). Acute aerobic exercise significantly decreased insulin concentrations (mean difference: − 18.07 pmol/L; 95% CI, − 30.47

Journal article

Wallis GA, Chambers ES, 2021, UK Nutrition Research Partnership (NRP) workshop: Improving our understanding of the metabolic interplay between nutrition and physical activity (IN-PACT), NUTRITION BULLETIN, Vol: 46, Pages: 350-353, ISSN: 1471-9827

Journal article

Sharma R, Lu H, George J, Eslam M, Villanueva A, Ward C, Reeves HL, McCain M, Chambers E, Sands C, Maslen L, Lewis M, Ramaswami Ret al., 2021, Discriminatory changes in circulating lipid and small molecule metabolites in patients with MAFLD associated hepatocellular cancer, Publisher: ELSEVIER, Pages: S490-S490, ISSN: 0168-8278

Conference paper

Petropoulou K, Salt LJ, Edwards CH, Warren FJ, Garcia-Perez I, Chambers ES, Alshaalan R, Khatib M, Perez-Moral N, Cross KL, Kellingray L, Stanley R, Koev T, Khimyak YZ, Narbad A, Penney N, Serrano-Contreras JI, Charalambides MN, Miguens Blanco J, Castro Seoane R, McDonald JAK, Marchesi JR, Holmes E, Godsland IF, Morrison DJ, Preston T, Domoney C, Wilde PJ, Frost GSet al., 2020, A natural mutation in Pisum sativum L. (pea) alters starch assembly and improves glucose homeostasis in humans, Nature Food

Journal article

Willis ND, Lloyd AJ, Xie L, Stiegler M, Tailliart K, Garcia-Perez I, Chambers ES, Beckmann M, Draper J, Mathers JCet al., 2020, Design and characterisation of a randomized food intervention that mimics exposure to a typical UK diet to provide urine samples for identification and validation of metabolite biomarkers of food intake, Frontiers in Nutrition, Vol: 7, Pages: 1-16, ISSN: 2296-861X

Poor dietary choices are major risk factors for obesity and non-communicable diseases, which places an increasing burden on healthcare systems worldwide. To monitor the effectiveness of healthy eating guidelines and strategies, there is a need for objective measures of dietary intake in community settings. Metabolites derived from specific foods present in urine samples can provide objective biomarkers of food intake (BFIs). Whilst the majority of biomarker discovery/validation studies have investigated potential biomarkers for single foods only, this study considered the whole diet by using menus that delivered a wide range of foods in meals that emulated conventional UK eating patterns. Fifty-one healthy participants (range 19–77 years; 57% female) followed a uniquely designed, randomized controlled dietary intervention, and provided spot urine samples suitable for discovery of BFIs within a real-world context. Free-living participants prepared and consumed all foods and drinks in their own homes and were asked to follow the protocols for meal consumption and home urine sample collection. This study also assessed the robustness, and impact on data quality, of a minimally invasive urine collection protocol. Overall the study design was well-accepted by participants and concluded successfully without any drop outs. Compliance for urine collection, adherence to menu plans, and observance of recommended meal timings, was shown to be very high. Metabolome analysis using mass spectrometry coupled with data mining demonstrated that the study protocol was well-suited for BFI discovery and validation. Novel, putative biomarkers for an extended range of foods were identified including legumes, curry, strongly-heated products, and artificially sweetened, low calorie beverages. In conclusion, aspects of this study design would help to overcome several current challenges in the development of BFI technology. One specific attribute was the examination of BFI generalizabil

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

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

Sharma R, Valls PO, Inglese M, Dubash S, Chen M, Gabra H, Montes A, Challapalli A, Arshad M, Tharakan G, Chambers E, Cole T, Lozano-Kuehne JP, Barwick TD, Aboagye EOet al., 2020, [18F]Fluciclatide PET as a biomarker of response to combination therapy of pazopanib and paclitaxel in platinum-resistant/refractory ovarian cancer, European Journal of Nuclear Medicine and Molecular Imaging, Vol: 47, Pages: 1239-1251, ISSN: 0340-6997

BACKGROUND: Angiogenesis is a driver of platinum resistance in ovarian cancer. We assessed the effect of combination pazopanib and paclitaxel followed by maintenance pazopanib in patients with platinum-resistant/refractory ovarian cancer. Integrins αvβ3 and αvβ5 are both upregulated in tumor-associated vasculature. [18F]Fluciclatide is a novel PET tracer that has high affinity for integrins αvβ3/5, and was used to assess the anti-angiogenic effect of pazopanib. PATIENTS AND METHODS: We conducted an open-label, phase Ib study in patients with platinum-resistant/refractory ovarian cancer. Patients received 1 week of single-agent pazopanib (800 mg daily) followed by combination therapy with weekly paclitaxel (80 mg/m2). Following completion of 18 weeks of combination therapy, patients continued with single-agent pazopanib until disease progression. Dynamic [18F]fluciclatide-PET imaging was conducted at baseline and after 1 week of pazopanib. Response (RECIST 1.1), toxicities, and survival outcomes were recorded. Circulating markers of angiogenesis were assessed with therapy. RESULTS: Fourteen patients were included in the intention-to-treat analysis. Complete and partial responses were seen in seven patients (54%). Median progression-free survival (PFS) was 10.63 months, and overall survival (OS) was 18.5 months. Baseline [18F]fluciclatide uptake was predictive of long PFS. Elevated baseline circulating angiopoietin and fibroblast growth factor (FGF) were predictive of greater reduction in SUV60,mean following pazopanib. Kinetic modeling of PET data indicated a reduction in K1 and Ki following pazopanib indicating reduced radioligand delivery and retention. CONCLUSIONS: Combination therapy followed by maintenance pazopanib is effective and tolerable in platinum-resistant/refractory ovarian cancer. [18F]Fluciclatide-PET uptake parameters predict clinical outcome with pazopanib therapy indicating an anti

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

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 <i>starch branching enzyme IIa</i> and <i>b</i> mutant wheat on glycaemic response <i>in vitro</i> and <i>in vivo</i>: a randomised controlled pilot study, FOOD & FUNCTION, Vol: 11, Pages: 617-627, ISSN: 2042-6496

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

Sharma R, Valls PO, Inglese M, Dubash S, Chen M, Gabra H, Montes A, Challapalli A, Arshad M, Thakaran G, Chambers E, Cole T, Lozano-Kuehne J, Barwick TD, Aboagye EOet al., 2019, [<SUP>18</SUP>F]fluciclatide Pet As A Biomarker Of Response To Combination Therapy Of Pazopanib And Paclitaxel In Platinum-resistant/refractory Ovarian Cancer, 32nd Annual Congress of the European-Association-of-Nuclear-Medicine (EANM), Publisher: SPRINGER, Pages: S223-S223, ISSN: 1619-7070

Conference paper

Gibson R, Eriksen R, Chambers E, Gao H, Aresu M, Heard A, Chan Q, Elliott P, Frost Get al., 2019, Intakes and food sources of dietary fibre and their associations with measures of body composition and inflammation in UK adults: Cross-sectional analysis of the Airwave Health Monitoring Study, Nutrients, Vol: 11, ISSN: 2072-6643

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.

Journal article

Sukkar A, Lett A, Frost G, Chambers Eet al., 2019, Regulation of energy expenditure and substrate oxidation by short chain fatty acids, Journal of Endocrinology, Vol: 242, Pages: R1-R8, ISSN: 1479-6805

Short-chain fatty acids (SCFAs) are metabolites produced from the fermentation of dietary fibre by the gut microbiota. High-fibre diets have been associated with lower weight gain and a number of reports have therefore investigated if these positive effects of a dietary fibre on body weight can be replicated through the direct administration of SCFAs. Many of these studies have reported that SCFAs can prevent or attenuate long-term body weight gain by increasing energy expenditure through increased lipid oxidation. The aim of the present review is to therefore evaluate the current evidence for an effect of SCFAs on whole-body energy expenditure and to assess the potential underlying mechanisms. The available data highlights that SCFAs can exert multiple effects at various organ and tissue sites that would cumulatively raise energy expenditure via a promotion of lipid oxidation. In conclusion, the present review proposes that dietary interventions and other therapies that augment gut-derived SCFAs and systemic availability may present an effective strategy to improve long-term energy balance and body weight management.

Journal article

Chambers E, Byrne C, Rugyendo A, Morrison D, Preston T, Tedford C, Bell J, Thomas L, Akbar A, Riddell N, Sharma R, Thursz M, Manousou P, Frost Get al., 2019, The effects of dietary supplementation with inulin and inulin-propionate ester on hepatic steatosis in adults with non-alcoholic fatty liver disease, Diabetes, Obesity and Metabolism, Vol: 21, Pages: 372-376, ISSN: 1462-8902

The short chain fatty acid (SCFA) propionate, produced through fermentation of dietary fibre by the gut microbiota, has been shown to alter hepatic metabolic processes that reduce lipid storage. We aimed to investigate the impact of raising colonic propionate production on hepatic steatosis in adults with non‐alcoholic fatty liver disease (NAFLD). Eighteen adults were randomised to receive 20g/day of an inulin‐propionate ester (IPE), designed to deliver propionate to the colon, or an inulin‐control for 42‐days in a parallel design. The change in intrahepatocellular lipid (IHCL) following the supplementation period was not different between groups (P=0.082), however IHCL significantly increased within the inulin‐control group (20.9±2.9 to 26.8±3.9%; P=0.012; n=9), which was not observed within the IPE group (22.6±6.9 to 23.5±6.8%; P=0.635; n=9). The predominant SCFA from colonic fermentation of inulin is acetate, which in a background of NAFLD and a hepatic metabolic profile that promotes fat accretion, may provide surplus lipogenic substrate to the liver. The increased colonic delivery of propionate from IPE appears to attenuate this acetate‐mediated increase in IHCL.

Journal article

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