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ObjectivesEnvironmental enteropathy (EE) is a subclinical disorder highly prevalent in tropical and disadvantaged populations and is thought to play a role in growth faltering in children, poor responses to oral vaccines, and micronutrient deficiencies. This study aims to evaluate the potential of a non-invasive breath test based on stable isotopes for evaluation of impaired digestion and absorption of sucrose in EE.MethodsWe optimized a 13C-sucrose breath test (13C-SBT) in 19 young adults in Glasgow, United Kingdom. In a further experiment (in 18 adults) we validated the 13C-SBT using Reducose, an intestinal glucosidase inhibitor. We then compared the 13C-SBT to intestinal mucosal morphometry, immunostaining for sucrose-isomaltase (SI) expression, and SI activity in 24 Zambian adults with EE.ResultsFully labeled sucrose (0.3 mg/kg) provided clear breath enrichment signals over 2–3 h in both British and Zambian adults, more than fivefold higher than naturally enriched sucrose. Reducose dramatically impaired 13C-sucrose digestion, reducing 4 h 13CO2 breath recovery by > 50%. Duodenal biopsies in Zambian adults confirmed the presence of EE, and SI immunostaining was present in 16/24 adults. The kinetics of 13CO2 evolution were consistently faster in participants with detectable SI immunostaining. Although sucrase activity was strongly correlated with villus height (r = 0.72; P < 0.05) after adjustment for age, sex and body mass index, there were no correlations between 13C-SBT and villus height or measured sucrase activity in pinch biopsies.ConclusionA 13C-SBT was developed which was easy to perform, generated clear enrichment of 13CO2 in breath samples, and clearly reports sucrase activity. Further work is needed to validate it and understand its applications in evaluating EE.

Introduction: \ud Environmental enteropathy (EE) is suspected to be a cause of growth faltering in children with sustained exposure to enteric pathogens, typically in resource-limited settings. A major hindrance to EE research is the lack of sensitive, non-invasive biomarkers. Current biomarkers measure intestinal permeability and inflammation, but not the functional capacity of the gut. Australian researchers have demonstrated proof of concept for an EE breath test based on using naturally 13C-enriched sucrose, derived from maize, to assay intestinal sucrase activity, a digestive enzyme that is impaired in villus blunting. Here, we describe a coordinated research project to optimise, validate and evaluate the usability of a breath test protocol based on highly enriched 13C-sucrose to quantify physiological dysfunction in EE in relevant target populations.\ud \ud Methods and analysis: \ud We use the 13C-sucrose breath test (13C-SBT) to evaluate intestinal sucrase activity in two phases. First, an optimisation and validation phase will (1) confirm that a 13C-SBT using highly enriched sucrose tracers reports similar information to the naturally enriched 13C-SBT; (2) examine the dose–response relationship of the test to an intestinal sucrase inhibitor; (3) validate the 13C-SBT in paediatric coeliac disease (4) validate the highly enriched 13C-SBT against EE defined by biopsy in adults and (5) validate the 13C-SBT against EE defined by the urinary lactulose:rhamnose ratio (LR) among children in Peru. Second, a cross-sectional study will be conducted in six resource-limited countries (Bangladesh, India, Jamaica, Kenya, Peru and Zambia) to test the usability of the optimised 13C-SBT to assess EE among 600 children aged 12–15 months old.\ud \ud Ethics and dissemination: \ud Ethical approval will be obtained from each participating study site. By working as a consortium, the test, if shown to be informative of EE, will demonstrate strong evidence for utility across diverse, low-income and middle-income country paediatric populations.\ud \ud Trial registration number: NCT04109352; Pre-results.

The world’s population is expanding, leading to an increased global requirement for dietary protein to support health and adaptation in various populations. Though a strong evidence base supports the nutritional value of animal-derived dietary proteins, mounting challenges associated with sustainability of these proteins have led to calls for the investigation of alternative, non–animal-derived dietary protein sources. Mycoprotein is a sustainably produced, protein-rich, high-fiber, whole food source derived from the fermentation of fungus. Initial investigations in humans demonstrated that mycoprotein consumption can lower circulating cholesterol concentrations. Recent data also report improved acute postprandial glycemic control and a potent satiety effect following mycoprotein ingestion. It is possible that these beneficial effects are attributable to the amount and type of dietary fiber present in mycoprotein. Emerging data suggest that the amino acid composition and bioavailability of mycoprotein may also position it as a promising dietary protein source to support skeletal muscle protein metabolism. Mycoprotein may be a viable dietary protein source to promote training adaptations in athletes and the maintenance of muscle mass to support healthy aging. Herein, current evidence underlying the metabolic effects of mycoprotein is reviewed, and the key questions to be addressed are highlighted.

Short‐chain fatty acids (SCFAs), produced from fermentation of dietary fibre by the gut microbiota, have been suggested to modulate energy metabolism. Previous work using rodent models has demonstrated that oral supplementation of the SCFA propionate raises resting energy expenditure (REE) by promoting lipid oxidation. The objective of the present study was to investigate the effects of oral sodium propionate on REE and substrate metabolism in humans. Eighteen healthy volunteers (9 women and 9 men; age 25 ± 1 years; body mass index 24.1 ± 1.2 kg/m2) completed 2 study visits following an overnight fast. Tablets containing a total of 6845 mg sodium propionate or 4164 mg sodium chloride were provided over the 180‐minute study period in random order. REE and substrate oxidation were assessed by indirect calorimetry. Oral sodium propionate administration increased REE (0.045 ± 0.020 kcal/min; P = .036); this was accompanied by elevated rates of whole‐body lipid oxidation (0.012 ± 0.006 g/min; P = .048) and was independent of changes in glucose and insulin concentrations. Future studies are warranted to determine whether the acute effects of oral sodium propionate on REE translate into positive improvements in long‐term energy balance in humans.

Purpose: This study compared the co-ingestion of glucose and fructose on exogenous and endogenous substrate oxidation during prolonged exercise at terrestrial high altitude (HA) versus sea level, in women.\ud \ud Method Five women completed two bouts of cycling at the same relative workload (55% Wmax) for 120 minutes on acute exposure to HA (3375m) and at sea level (~113m). In each trial, participants ingested 1.2 g.min-1 of glucose (enriched with 13C glucose) and 0.6 g.min-1 of fructose (enriched with 13C fructose) before and every 15 minutes during exercise. Indirect calorimetry and isotope ratio mass spectrometry were used to calculate fat oxidation, total and exogenous carbohydrate oxidation, plasma glucose oxidation and endogenous glucose oxidation derived from liver and muscle glycogen.\ud \ud Results The rates and absolute contribution of exogenous carbohydrate oxidation was significantly lower at HA compared with sea level (ES>0.99, P

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 randomized to receive 20 g/d 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 the 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.

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.

Background: The appetite-regulating effects of non-digestible carbohydrates (NDC) have in part previously been attributed to their effects on intestinal transit rates as well as microbial production of short chain fatty acids (SCFA). Increased colonic production of the SCFA propionate has been shown to reduce energy intake and stimulate gut hormone secretion acutely in humans.\ud \ud Objective: We investigated the effect of the propiogenic NDC, L-rhamnose, on gastrointestinal transit times using a combined 13CO2/H2 breath test. We hypothesised that L-rhamnose would increase plasma propionate leading to a reduction in appetite, independent of changes in gastrointestinal transit times.\ud \ud Design: We used a dual 13C octanoic acid/lactose 13C-ureide breath test combined with breath H2 to measure intestinal transit times following the consumption of 25g/d L-rhamnose, compared with inulin and cellulose, in 10 healthy humans in a randomised cross-over pilot study. Gastric emptying (GE) and oro-caecal transit times (OCTT) were derived from the breath 13C data and compared with breath H2. Plasma SCFA and peptide YY (PYY) were also measured alongside subjective measures of appetite.\ud \ud Results: L-rhamnose significantly slowed GE rates (by 19.5min) but there was no difference in OCTT between treatments. However, breath H2 indicated fermentation of L-rhamnose before it reached the caecum. OCTT was highly correlated with breath H2 for inulin but not for L-rhamnose or cellulose. L-rhamnose consumption significantly increased plasma propionate and PYY but did not significantly reduce subjective appetite measures.\ud \ud Conclusions: The NDCs tested had a minimal effect on intestinal transit time. Our data suggest that L-rhamnose is partially fermented in the small intestine and that breath H2 reflects the site of gastrointestinal fermentation and is only a reliable marker of OCTT for certain NDCs (e.g. inulin). Future studies should focus on investigating the appetite-suppressing potential of L-rhamnose and verifying the findings in a larger cohort.

This study investigated the effect of carbohydrate (CHO) dose and composi-tion on fuel selection during exercise, specifically exogenous and endogenous(liver and muscle) CHO oxidation. Ten trained males cycled in a double-blindrandomized order on 5 occasions at 77%_VO2maxfor 2 h, followed by a30-min time-trial (TT) while ingesting either 60 g�h�1(LG) or 75 g�h�113C-glucose (HG), 90 g�h�1(LGF) or 112.5 g�h�113C-glucose-13C-fructose ([2:1]HGF) or placebo. CHO doses met or exceed reported intestinal transportersaturation for glucose and fructose. Indirect calorimetry and stable mass iso-tope [13C] tracer techniques were utilized to determine fuel use. TT perfor-mance was 93% “likely/probable” to be improved with LGF compared withthe other CHO doses. Exogenous CHO oxidation was higher for LGF andHGF compared with LG and HG (ES>1.34,P0.90,P=0.024–0.17). In conclusion, there was no lin-ear dose response for CHO ingestion, with 90 g�h�1of glucose-fructose beingoptimal in terms of TT performance and fuel selection

Clostridium difficile is the dominant cause of pseudomembranous colitis in nosocomial environments. C. difficile infection (CDI) generally affects elderly (≥ 65) hospital in-patients who have received broad spectrum antimicrobial treatment. CDI has a 30% risk of reinfection and subsequent 60% risk of relapse thereafter, leading to a high economic burden of over 7 billion pounds sterling and over 900,000 cases in the USA and Europe per annum. With the long-term consequences of faecal transplantation currently unknown, and limited spectrum of effective antibiotics, there is an urgent requirement for alternative means of preventing and treating CDI in high risk individuals. Metagenomics has recently improved our understanding of the colonisation resistance barrier and how this could be optimised. pH, oxidation-reduction potentials and short chain fatty acids have been suggested to inhibit C. difficile growth and toxin production in vitro and in vivo studies. This review aims to pull together the evidence in support of a colonisation resistance barrier against CDI.