Exercise is one of the external factors associated with impairment of intestinal integrity, possibly leading to increased permeability and altered absorption. Here, we aimed to examine to what extent endurance exercise in the glycogen‐depleted state can affect intestinal permeability toward small molecules and protein‐derived peptides in relation to markers of intestinal function. Eleven well‐trained male volunteers (27 ± 4 years) ingested 40 g of casein protein and a lactulose/rhamnose (L/R) solution after an overnight fast in resting conditions (control) and after completing a dual – glycogen depletion and endurance – exercise protocol (first protocol execution). The entire procedure was repeated 1 week later (second protocol execution). Intestinal permeability was measured as L/R ratio in 5 h urine and 1 h plasma. Five‐hour urine excretion of betacasomorphin‐7 (BCM7), postprandial plasma amino acid levels, plasma fatty acid binding protein 2 (FABP‐2), serum pre‐haptoglobin 2 (preHP2), plasma glucagon‐like peptide 2 (GLP2), serum calprotectin, and dipeptidylpeptidase‐4 (DPP4) activity were studied as markers for excretion, intestinal functioning and recovery, inflammation, and BCM7 breakdown activity, respectively. BCM7 levels in urine were increased following the dual exercise protocol, in the first as well as the second protocol execution, whereas 1 h‐plasma L/R ratio was increased only following the first exercise protocol execution. FABP2, preHP2, and GLP2 were not changed after exercise, whereas calprotectin increased. Plasma citrulline levels following casein ingestion (iAUC) did not increase after exercise, as opposed to resting conditions. Endurance exercise in the glycogen depleted state resulted in a clear increase of BCM7 accumulation in urine, independent of DPP4 activity and intestinal permeability. Therefore, strenuous exercise could have an effect on the amount of food‐derived bioactive peptides crossing the epithelial barrier. The health consequence of increased passage needs more in depth studies.
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Background & aims Plasma citrulline concentration is considered to be a marker for enterocyte metabolic mass and to reflect its reduction as may occur during intestinal dysfunction. Strenuous exercise can act as a stressor to induce small intestinal injury. Our previous studies suggest that this comprises the intestinal ability to produce citrulline from a glutamine-rich protein bolus. In this study we investigated the effects of different exercise intensities and hydration state on citrulline and iFABP levels following a post-exercise glutamine bolus in healthy young men. Methods Fifteen healthy young men (20–35 yrs, VO2 max 56.9 ± 3.9 ml kg−1 min−1) performed in a randomly assigned cross-over design, a rest (protocol 1) and four cycle ergometer protocols. The volunteers cycled submaximal at different percentages of their individual pre-assessed maximum workload (Wmax): 70% Wmax in hydrated (protocol 2) and dehydrated state (protocol 3), 50% Wmax (protocol 4) and intermittent 85/55% Wmax in blocks of 2 min (protocol 5). Immediately after 1 h exercise or rest, subjects were given a glutamine bolus with added alanine as an iso-caloric internal standard (7.5 g of each amino acid). Blood samples were collected before, during and after rest or exercise, up to 24 h post onset of the experiment. Amino acids and urea were analysed as metabolic markers, creatine phosphokinase and iFABP as markers of muscle and intestinal damage, respectively. Data were analysed using a multilevel mixed linear statistical model. p values were corrected for multiple testing. Results Citrulline levels already increased before glutamine supplementation during normal hydrated exercise, while this was not observed in the dehydrated and rest protocols. The low intensity exercise protocol (50% Wmax) showed the highest increase in citrulline levels both during exercise (43.83 μmol/L ± 2.63 (p < 0.001)) and after glutamine consumption (50.54 μmol/L ± 2.62) compared to the rest protocol (28.97 μmol/L ± 1.503 and 41.65 μmol/L ± 1.96, respectively, p < 0.05). However, following strenuous exercise at 70% Wmax in the dehydrated state, citrulline levels did not increase during exercise and less after the glutamine consumption when compared to the resting condition and hydrated protocols. In line with this, serum iFABP levels were the highest with the strenuous dehydrated protocol (1443.72 μmol/L ± 249.9, p < 0.001), followed by the high intensity exercise at 70% Wmax in the hydrated condition. Conclusions Exercise induces an increase in plasma citrulline, irrespective of a glutamine bolus. The extent to which this occurs is dependent on exercise intensity and the hydration state of the subjects. The same holds true for both the post-exercise increase in citrulline levels following glutamine supplementation and serum iFABP levels. These data indicate that citrulline release during exercise and after an oral glutamine bolus might be dependent on the intestinal health state and therefore on intestinal functionality. Glutamine is known to play a major role in intestinal physiology and the maintenance of gut health and barrier function. Together, this suggests that in clinical practice, a glutamine bolus to increase citrulline levels after exercise might be preferable compared to supplementing citrulline itself. To our knowledge this is the first time that exercise workload-related effects on plasma citrulline are reported in relation to intestinal damage.
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Introduction: Strenuous physical stress induces a range of physiological responses, the extent depending, among others, on the nature and severity of the exercise, a person’s training level and overall physical resilience. This principle can also be used in an experimental set-up by measuring time-dependent changes in biomarkers for physiological processes. In a previous report, we described the effects of workload delivered on a bicycle ergometer on intestinal functionality. As a follow-up, we here describe an analysis of the kinetics of various other biomarkers. Aim: To analyse the time-dependent changes of 34 markers for different metabolic and immunological processes, comparing four different exercise protocols and a rest protocol. Methods: After determining individual maximum workloads, 15 healthy male participants (20–35 years) started with a rest protocol and subsequently performed (in a cross-over design with 1-week wash-out) four exercise protocols of 1-h duration at different intensities: 70% Wmax in a hydrated and a mildly dehydrated state, 50% Wmax and intermittent 85/55% Wmax in blocks of 2 min. Perceived exertion was monitored using the Borg’ Rating of Perceived Exertion scale. Blood samples were collected both before and during exercise, and at various timepoints up to 24 h afterward. Data was analyzed using a multilevel mixed linear model with multiple test correction. Results: Kinetic changes of various biomarkers were exercise-intensity-dependent. Biomarkers included parameters indicative of metabolic activity (e.g., creatinine, bicarbonate), immunological and hematological functionality (e.g., leukocytes, hemoglobin) and intestinal physiology (citrulline, intestinal fatty acid-binding protein, and zonulin). In general, responses to high intensity exercise of 70% Wmax and intermittent exercise i.e., 55/85% Wmax were more pronounced compared to exercise at 50% Wmax. Conclusion: High (70 and 55/85% Wmax) and moderate (50% Wmax) intensity exercise in a bicycle ergometer test produce different time-dependent changes in a broad range of parameters indicative of metabolic activity, immunological and hematological functionality and intestinal physiology. These parameters may be considered biomarkers of homeostatic resilience. Mild dehydration intensifies these time-related changes. Moderate intensity exercise of 50% Wmax shows sufficient physiological and immunological responses and can be employed to test the health condition of less fit individuals.
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In the last decade, the concept on interactions between humans, animals and their environment has drastically changed, endorsed by the One Health approach that recognizes that health of humans and animals are inextricably linked. Consideration of welfare of livestock has increased accordingly and with it, attention into the possibilities to improve livestock health via natural, more balanced nutrition is expanding. Central to effects of healthy nutrition is an optimal gastrointestinal condition which entails a well-balanced functional local immune system leading to a resilient state of well-being. This project proposal, GITools, aims to establish a toolbox of in vitro assays to screen new feed ingredients for beneficial effects on gastrointestinal health and animal well-being. GITools will focus on pig and chicken as important livestock species present in high quantities and living in close proximity to humans. GITools builds on intestinal models (intestinal cell lines and stem cell-derived organoids), biomarker analysis, and in vitro enzymatic and microbial digestion models of feed constituents. The concept of GITools originated from various individual contacts and projects with industry partners that produce animal feed (additives) or veterinary medicines. Within these companies, an urgent need exists for straightforward, well-characterized and standardized in vitro methods that provide results translatable to the in vivo situation. This to replace testing of new feed concepts in live animal. We will examine in vitro methods for their applicability with feed ingredients selected based on the availability of data from (previous) in vivo studies. These model compounds will include long and short chain fatty acids, oligosaccharides and herbal-derived components. GITools will deliver insights on the role of intestinal processes (e.g. dietary hormone production, growth of epithelial cells, barrier function and innate immune responses) in health and well-being of livestock animals and improve the efficiency of testing new feed products.
Om de prehabilitatiezorg betaalbaar te houden, is het van belang om zorg op maat te leveren. De wijze van aanbod is daarnaast van cruciaal belang voor het slagen van prehabilitatie. Niet elke patiënt heeft gesuperviseerde training nodig. Sommige patiënten hebben voldoende aan leefstijladviezen via een mobiele app, terwijl anderen wél gesuperviseerde begeleiding nodig hebben van een zorgprofessional.Doel In dit project gaan we ‘prehabilitatie fenotypes’ ontwikkelen van kandidaten voor prehabilitatie op basis van persoonlijke kenmerken. Door deze subgroepen te onderscheiden kan vervolgens bepaald worden welke vorm van ondersteuning (denk bijvoorbeeld aan gesuperviseerd, digitaal of blended) per fenotype het meest geschikt is. Met behulp van deze prehabilitatie fenotypes krijgen zorgprofessionals in de praktijk concrete handvatten om prehabilitatiezorg op maat voor te schrijven. Hiermee worden er twee vliegen in één klap geslagen: gepersonaliseerde zorg én betaalbare zorg. Resultaten We gaan een cross-sectionele data-analyse uitvoeren op (in ieder geval) twee bestaande datasets. Er zal tevens geïnventariseerd worden of er aanvullende geschikte databases zijn in andere prehabilitatie-onderzoekscentra die meegenomen kunnen worden in de analyses. Beter Voorbereid: Beter Voorbereid is een multicentrum RCT naar het effect van een mobiele applicatie waarmee patiënten voor en na hun operatie adviezen krijgen over het optimaliseren van hun leefstijl en over het omgaan met stress rondom de operatie. Dit project is gesubsidieerd door SIA RAAK MKB. PAM-ONCO: PAM-ONCO is een observationele studie in het UMC Utrecht naar het verloop van het beweeggedrag en het fysiek functioneren van patiënten die een gastro-intestinale oncologische operatie ondergaan. Looptijd 15 mei 2022 - 31 december 2023 Aanpak Dit project wordt in samenwerking met het UMC Utrecht uitgevoerd en bestaat uit meerdere fases: Fase 1: Determinanten voor de analyse Op basis van consensus zal bepaald worden welke variabelen daadwerkelijk invloed kunnen hebben op de manier van ondersteuning van patiënten in de preoperatieve fase. Daarom zullen er in deze fase 1 of 2 consensusmeetings worden georganiseerd met experts om te komen tot een definitieve lijst voor de variabelen. Fase 2: Analyses De variabelen (zie fase 1) uit beide studies zullen worden gestandaardiseerd, samengevoegd en klaargemaakt voor data-analyses. Het plan voor de clusteranalyses wordt besproken met experts op dit gebied en op basis van hun adviezen geoptimaliseerd. Vervolgens zullen de analyses worden uitgevoerd om fenotypes te vormen. Fase 3: Vergelijken van klinische uitkomsten en patiëntkarakteristieken tussen fenotypes Na het bepalen van de fenotypes, zullen de klinische uitkomsten en patiëntkarakteristieken tussen de fenotypes worden vergeleken. Er zal een uitgebreidere beschrijving worden gemaakt van de kenmerken van patiënten binnen elk fenotype. De beschrijving van de fenotypes biedt de basis van de volgende fase. Fase 4: Bepalen welke fenotypes baat kunnen hebben bij welke interventies en begeleiding In vier focusgroepen (twee met patiënten en twee met experts) zal bepaald worden welk type ondersteuning/begeleiding en prehabilitatie-interventies past bij de verschillende fenotypes zoals gevonden in fase 2.
Om de prehabilitatiezorg betaalbaar te houden, is het van belang om zorg op maat te leveren. De wijze van aanbod is daarnaast van cruciaal belang voor het slagen van prehabilitatie. Niet elke patiënt heeft gesuperviseerde training nodig. Sommige patiënten hebben voldoende aan leefstijladviezen via een mobiele app, terwijl anderen wél gesuperviseerde begeleiding nodig hebben van een zorgprofessional.
