Tom Preston

Background: Overweight and obesity affect over 60% of the United Kingdom population and constitute a major risk factor for the development of comorbidities. Preventing weight gain in periods of life where there is an elevated risk of adipose tissue expansion could be beneficial in preventing associated diseases in later life. This study investigated the impact of inulin-propionate ester on the prevention of weight gain in young people who were at risk of gaining weight. Objectives: To investigate the impact of increasing colonic production of the short-chain fatty acid propionate on preventing body weight gain, in younger adults, over 12 months. Several underpinning mechanisms were investigated in a substudy. Design: iPREVENT was a randomised, parallel-group, placebo-controlled, double-blind trial, designed with 90% power to detect a 2 kg between-arm difference in weight gain at 12 months. Setting: This trial was performed at the Imperial Clinical Research Facility in London and the University of Glasgow Clinical Research Facility. Participants: Participants were 20–40 years old, with a body mass index of 24.0–27.0 kg/m² if of South Asian ethnicity or 25.0–30.0 kg/m² if non-South Asian. Participants were also required to have at least one of the following risk factors: weight gain in the past year, low physical activity, low intake of fruit and vegetables or high intake of sugar-sweetened beverages. A total of 270 participants (135 per arm) were randomised. Intervention: Participants were randomised to either 10 g/day inulin-propionate ester or 10 g/day inulin control (fermentable oligosaccharide) consumed daily for 12 months. Main outcome measure: The primary outcome was weight gain from baseline to 12 months. Results: The mean (± standard deviation) body weight at baseline for inulin was 79.1 kg ± 10.6 (n = 135) and inulin-propionate ester 79.6 kg ± 10.9 (n = 135). At 12 months body weight was 78.9 kg ± 11.8 (n = 114) and 81.4 kg ± 11.9 (n = 112) for inulin and inulin-propionate ester, respectively. The baseline-adjusted mean difference in weight gain was 1.02 (95% confidence intervals −0.37 to 2.41) kg for inulin-propionate ester versus inulin control. Of the secondary outcomes, the confidence interval cautiously supports differences in fat-free mass; 1.07 kg (0.21 to 1.93) (N = 226), body water; 0.72 kg (0.1 to 1.33) (N = 226) and fasting glucose; 0.11 mmol/l (0.01 to 0.21) (N = 191). Compliance with inulin-propionate ester treatment of ≥ 50% over 12 months was 63% (n = 135). There were no unexpected adverse or serious adverse events. Limitations: This study aimed to explore the efficacy of enhanced propionate production above background fermentation. It could be argued a negative control (a non-fermentable substrate e.g. cellulose) would have been more suitable. Metabolomic analysis of compliance could only be conducted on a subsection of the study population. There was no intention to conduct follow-up assessments on participants beyond their 12-month visit. Conclusions: In adults below the age of 40 years, inulin-propionate ester did not affect weight gain compared with the control. Future work: Previously we observed that inulin-propionate ester prevented weight gain in older adults, but not in this younger cohort. We aim to investigate the variation in responses between these age groups. Trial registration: This trial is registered as ISRCTN16299902. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation (EME) programme (NIHR award ref: 15/185/16) and is published in full in Efficacy and Mechanism Evaluation; Vol. 12, No. 8. See the NIHR Funding and Awards website for further award information.

Background: The use of plant protein intrinsically labelled with stable isotopes provides an innovative solution to assess the efficiency of protein intake by humans. Here, the incorporation of H-2 has been applied to intrinsically labelled plant protein in the common bean. This study aimed to evaluate which is the best phenological phase of seed maturation to incorporate the heavy hydrogen isotope H-2 into seed amino acids. Common beans (Phaseolus vulgaris L.) were grown in pots, then, after 50 days sowing, (H2O)-H-2 dissolved in irrigation water was applied, then again at an interval of either 3, 6, 9, and 12 days. Results: Applications of (H2O)-H-2 at 6, 9, and 12 days after the first application, in the full-flowering stage, were the best treatments for enriching protein-bound amino acids in the bean seed with H-2. Conclusion: All treatments resulted in enrichment above 500 ppm, so the treatments (quantity and timing of (H2O)-H-2 addition) were deemed successful for enriching bean seeds. This makes the intrinsically labelled seeds suitable for preparing test meals to assess the digestion and essential amino acid absorption of common bean amino acids in human subjects.

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 (<40 years old) adults over 12 months, whilst also investigating several complementary mechanisms that may explain the prevention of weight gain and improved long-term energy balance from consuming IPE. 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, 29th January 2019). Upon completion, the trial results will be published in peer-reviewed journals and presented at scientific conferences. Trial registration number: ISRCTN16299902, 1st March 2018.

Milk is an important high-quality animal protein source in low- and middle-income countries (LMICs). Although the true ileal digestibility and absorption of milk has been shown to be high in French adults, this may be lower in individuals from LMICs who are at risk of environmental enteropathy. To determine the true ileal indispensable amino acid (IAA) digestibility of intrinsically labeled goat milk protein in South Indian women of reproductive age (WRA), using the dual-isotope tracer technique, and to measure intestinal absorption of amino acid and inert sugar in the same participants using L-allo-isoleucine and a dual-sugar assay. Milk with ²H-labeled protein collected from a lactating goat fed intrinsically ²H-labeled fodder (maize and cowpea) was spray dried. Labeled milk protein was administered in a plateau feeding protocol to WRA with normal BMI, in whom urinary lactulose and mannitol recovery and the lactulose/mannitol ratio (LMR) were measured, to determine its true ileal IAA digestibility by the dual-isotope tracer technique with a reference U-¹³C–amino acid mixture. A phenylalanine absorption index was calculated from the plasma to meal ratio of ¹³C₉ phenylalanine within the digestibility protocol. On a separate day, the allo-isoleucine absorption index was estimated from the ratio of plasma allo-isoleucine enrichments after oral ¹³C₆-¹⁵N-L- and intravenous ²H₁₀-L-allo-isoleucine administration. The means ± SDs of true ileal IAA digestibility of goat milk protein, lactulose and mannitol recovery, LMR, allo-isoleucine and phenylalanine absorption index were 94.0 ± 2.9%, 0.09 ± 0.03%, 7.9 ± 2.3%, 0.012 ± 0.004, 88.4 ± 3.8% and 24.5 ± 1.6%, respectively. The LMR correlated with the allo-isoleucine absorption index (r_s = –0.93, P = 0.008). The true ileal digestibility of goat milk protein in South Indian WRA with normal intestinal absorptive function and integrity was comparable to earlier estimates in healthy French adults.

Elevated postprandial glucose (PPG) is a significant risk factor for non-communicable diseases globally. Currently, there is a limited understanding of how starch structures within a carbohydrate-rich food matrix interact with the gut luminal environment to control PPG. Here, we use pea seeds (Pisum sativum) and pea flour, derived from two near-identical pea genotypes (BC1/19RR and BC1/19rr) differing primarily in the type of starch accumulated, to explore the contribution of starch structure, food matrix and intestinal environment to PPG. Using stable isotope ¹³C-labelled pea seeds, coupled with synchronous gastric, duodenal and plasma sampling in vivo, we demonstrate that maintenance of cell structure and changes in starch morphology are closely related to lower glucose availability in the small intestine, resulting in acutely lower PPG and promotion of changes in the gut bacterial composition associated with long-term metabolic health improvements.

Polyphenols are often ingested alongside dietary fibres. They are both catabolised by, and may influence, the intestinal microbiota; yet, interactions between them and the impact on their resultant microbial products are poorly understood. Dietary fibres (inulin, pectin, psyllium, pyrodextrin, wheat bran, cellulose—three doses) were fermented in vitro with human faeces (n = 10) with and without rutin (20 µg/mL), a common dietary flavonol glycoside. Twenty-eight phenolic metabolites and short chain fatty acids (SCFA) were measured over 24 h. Several phenolic metabolites were produced during fibre fermentation, without rutin. With rutin, 3,4-dihydroxyphenylacetic acid (3,4diOHPAA), 3-hydroxyphenylacetic acid (3OHPAA), 3-(3 hydroxyphenyl)propionic acid (3OHPPA) and 3-(3,4-dihydroxyphenyl)propionic acid (3,4diOHPPA; DOPAC) were produced, with 3,4diOHPAA the most abundant, confirmed by fermentation of ¹³C labelled quercetin. The addition of inulin, wheat bran or pyrodextrin increased 3,4diOHPAA 2 2.5-fold over 24 h (p < 0.05). Rutin affected SCFA production, but this depended on fibre, fibre concentration and timepoint. With inulin, rutin increased pH at 6 h from 4.9 to 5.6 (p = 0.01) but increased propionic, butyric and isovaleric acid (1.9, 1.6 and 5-fold, p < 0.05 at 24 h). Interactions between fibre and phenolics modify production of phenolic acids and SCFA and may be key in enhancing health benefits.

Total energy expenditure (TEE) data in patients with early-stage cancer are scarce, precluding an understanding of energy requirements. The objective was to cross-sectionally characterize TEE in patients with colorectal cancer (CRC) and to compare measured TEE with energy recommendations. It was hypothesized that TEE would differ according to body mass, body composition, and physical activity level (PAL) and current energy recommendations would have poor individual-level accuracy. Patients with newly diagnosed CRC had resting energy expenditure (REE) measured by indirect calorimetry and TEE by doubly labeled water. Hypermetabolism was defined as REE > 110% of that predicted from the Mifflin St.-Jeor equation. Body composition was assessed via DXA. Physical activity was determined as the ratio of TEE to REE (TEE:REE) (PAL) and residual activity energy expenditure (RAEE). TEE was compared with energy recommendations of 25-30 kcal/d and Dietary Reference Intakes (DRIs) using Bland-Altman analyses. Patients were stratified according to median BMI, PAL, and sex-specific ratio of fat mass (FM) to fat-free mass (FFM). Twenty-one patients (M:F 14:7; mean ± SD BMI: 28.3 ± 4.9 kg/m2, age: 57 ± 12 y) were included. Most (n = 20) had stage II-III disease; 1 had stage IV. Approximately half (n = 11) were hypermetabolic; TEE was not different in those with hypermetabolism and REE as a percentage of predicted was not correlated with TEE. Mean ± SD TEE was 2473 ± 499 kcal/d (range: 1562-3622 kcal/d), or 29.7 ± 6.3 kcal/kg body weight (range: 20.4-48.5 kcal/kg body weight). Mean ± SD PAL was 1.43 ± 0.27. The energy recommendation of 25 kcal/kg underestimated TEE (-12.6% ± 16.5%, P = 0.002); all energy recommendations had wide limits of agreement (the smallest was DRI with measured PAL: -21.2% to 29.3%). Patients with higher BMI and FM:FFM had higher bias using kilocalories per kilogram recommendations; bias from several recommendations was frequently lower (i.e. underestimation) in patients with higher PAL and RAEE. TEE variability was not reflected in energy recommendations and error was related to body weight, body composition, and physical activity. This trial was registered at clinicaltrials.gov as NCT03131921.

Supplementation with inulin-propionate ester (IPE), which delivers propionate to the colon, suppresses ad libitum energy intake and stimulates the release of satiety hormones acutely in humans, and prevents weight gain. In order to determine whether IPE remains effective when incorporated into food products (FP), IPE needs to be added to a widely accepted food system. A bread roll and fruit smoothie were produced. Twenty-one healthy overweight and obese humans participated. Participants attended an acclimatisation visit and a control visit where they consumed un-supplemented food products (FP). Participants then consumed supplemented-FP, containing 10 g/d inulin or IPE for six days followed by a post-supplementation visit in a randomised crossover design. On study visits, supplemented-FP were consumed for the seventh time and ad libitum energy intake was assessed 420 min later. Blood samples were collected to assess hormones and metabolites. Resting energy expenditure (REE) was measured using indirect calorimetry. Taste and appearance ratings were similar between FP. Ad libitum energy intake was significantly different between treatments, due to a decreased intake following IPE-FP. These observations were not related to changes in blood hormones and metabolites. There was an increase in REE following IPE-FP. However, this effect was lost after correcting for changes in fat free mass. Our results suggest that IPE suppresses appetite and may alter REE following its incorporation into palatable food products.

Dietary fibers (DF) can prevent obesity in rodents fed a high-fat diet (HFD). Their mode of action is not fully elucidated, but the gut microbiota have been implicated. This study aimed to identify the effects of seven dietary fibers (barley beta-glucan, apple pectin, inulin, inulin acetate ester, inulin propionate ester, inulin butyrate ester or a combination of inulin propionate ester and inulin butyrate ester) effective in preventing diet-induced obesity and links to differences in cecal bacteria and host gene expression. Mice (n = 12) were fed either a low-fat diet (LFD), HFD or a HFD supplemented with the DFs, barley beta-glucan, apple pectin, inulin, inulin acetate ester, inulin propionate ester, inulin butyrate ester or a combination of inulin propionate ester and inulin butyrate ester for 8 weeks. Cecal bacteria were determined by Illumina MiSeq sequencing of 16S rRNA gene amplicons. Host responses, body composition, metabolic markers and gene transcription (cecum and liver) were assessed post intervention. HFD mice showed increased adiposity, while all of the DFs prevented weight gain. DF specific differences in cecal bacteria were observed. Results indicate that diverse DFs prevent weight gain on a HFD, despite giving rise to different cecal bacteria profiles. Conversely, common host responses to dietary fiber observed are predicted to be important in improving barrier function and genome stability in the gut, maintaining energy homeostasis and reducing HFD induced inflammatory responses in the liver.