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1.
Int J Mol Sci ; 25(7)2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-38612809

RESUMEN

Chorioamnionitis is a risk factor for necrotizing enterocolitis (NEC). Ureaplasma parvum (UP) is clinically the most isolated microorganism in chorioamnionitis, but its pathogenicity remains debated. Chorioamnionitis is associated with ileal barrier changes, but colonic barrier alterations, including those of the mucus barrier, remain under-investigated, despite their importance in NEC pathophysiology. Therefore, in this study, the hypothesis that antenatal UP exposure disturbs colonic mucus barrier integrity, thereby potentially contributing to NEC pathogenesis, was investigated. In an established ovine chorioamnionitis model, lambs were intra-amniotically exposed to UP or saline for 7 d from 122 to 129 d gestational age. Thereafter, colonic mucus layer thickness and functional integrity, underlying mechanisms, including endoplasmic reticulum (ER) stress and redox status, and cellular morphology by transmission electron microscopy were studied. The clinical significance of the experimental findings was verified by examining colon samples from NEC patients and controls. UP-exposed lambs have a thicker but dysfunctional colonic mucus layer in which bacteria-sized beads reach the intestinal epithelium, indicating undesired bacterial contact with the epithelium. This is paralleled by disturbed goblet cell MUC2 folding, pro-apoptotic ER stress and signs of mitochondrial dysfunction in the colonic epithelium. Importantly, the colonic epithelium from human NEC patients showed comparable mitochondrial aberrations, indicating that NEC-associated intestinal barrier injury already occurs during chorioamnionitis. This study underlines the pathogenic potential of UP during pregnancy; it demonstrates that antenatal UP infection leads to severe colonic mucus barrier deficits, providing a mechanistic link between antenatal infections and postnatal NEC development.


Asunto(s)
Corioamnionitis , Infecciones por Ureaplasma , Embarazo , Ovinos , Animales , Humanos , Femenino , Recién Nacido , Infecciones por Ureaplasma/complicaciones , Intestinos , Causalidad , Moco
2.
Psychosom Med ; 84(3): 306-312, 2022 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-34524263

RESUMEN

OBJECTIVE: Fullness is a cardinal symptom in functional dyspepsia (FD). The use of real-time symptom assessment might provide more insight into factors, such as daily stress, that can influence fullness. Therefore, this study aimed to use the experience sampling method (a real-time, repeated-measurement method making use of repeated questionnaires available at random moments for a limited amount of time) to assess the association between stress and fullness in patients with FD and healthy controls (HCs). METHODS: Thirty-five patients with FD (25 female, mean age = 44.7 years) and 34 HCs (24 female, mean age = 44.1 years) completed the experience sampling method (a maximum of 10 random moments per day) for 7 consecutive days. Stress and fullness were rated on an 11-point Numeric Rating Scale. Data between patients with FD and HCs were statistically compared using a Student samples t test and linear mixed-effects models with repeated measures (level 1) nested within participants (level 2). RESULTS: Average fullness scores were 2.23 (standard error = 0.37) points higher in patients with FD compared with HCs (p < .001). Average stress scores were 1.37 (standard error = 0.30) points higher in patients with FD compared with HCs (p = .002).In FD, fullness scores increased with 0.14 for every 1-point increase in concurrent stress scores (p = .010). Fullness scores at t = 0 increased with 0.12 for every 1-point increase in stress scores at t = -1 (p = .019). T = 0 stress scores were not associated with change in t = -1 fullness scores. No associations between concurrent symptom scores were found for HCs. CONCLUSIONS: Concurrent and preceding stress scores are positively associated with fullness scores in patients with FD, but not in HCs. These findings indicate that increased levels of stress may precede feelings of fullness in patients with FD. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT04204421.


Asunto(s)
Dispepsia , Adulto , Dispepsia/diagnóstico , Evaluación Ecológica Momentánea , Femenino , Estado de Salud , Humanos , Encuestas y Cuestionarios
3.
Br J Nutr ; 125(1): 92-100, 2021 01 14.
Artículo en Inglés | MEDLINE | ID: mdl-32660667

RESUMEN

Stimulation of gastrointestinal taste receptors affects eating behaviour. Intraduodenal infusion of tastants leads to increased satiation and reduced food intake, whereas intraileal infusion of tastants does not affect eating behaviour. Currently, it is unknown whether oral- or intragastric administration of tastants induces a larger effect on eating behaviour. This study investigated the effects of oral- and/or intragastric administration of quinine on food intake, appetite sensations and heart rate variability (HRV). In a blinded randomised crossover trial, thirty-two healthy volunteers participated in four interventions with a 1-week washout: oral placebo and intragastric placebo (OPGP), oral quinine and intragastric placebo (OQGP), oral placebo and intragastric quinine (OPGQ) and oral quinine and intragastric quinine (OQGQ). On test days, 150 min after a standardised breakfast, subjects ingested a capsule containing quinine or placebo and were sham-fed a mixture of quinine or placebo orally. At 50 min after intervention, subjects received an ad libitum meal to measure food intake. Visual analogue scales for appetite sensations were collected, and HRV measurements were performed at regular intervals. Oral and/or intragastric delivery of the bitter tastant quinine did not affect food intake (OPGP: 3273·6 (sem 131·8) kJ, OQGP: 3072·7 (sem 132·2) kJ, OPGQ: 3289·0 (sem 132·6) kJ and OQGQ: 3204·1 (sem 133·1) kJ, P = 0·069). Desire to eat and hunger decreased after OQGP and OPGQ compared with OPGP (P < 0·001 and P < 0·05, respectively), whereas satiation, fullness and HRV did not differ between interventions. In conclusion, sole oral sham feeding with and sole intragastric delivery of quinine decreased desire to eat and hunger, without affecting food intake, satiation, fullness or HRV.


Asunto(s)
Apetito/efectos de los fármacos , Agentes Aversivos/administración & dosificación , Ingestión de Alimentos/efectos de los fármacos , Quinina/administración & dosificación , Sensación/efectos de los fármacos , Administración Oral , Adolescente , Adulto , Anciano , Desayuno , Estudios Cruzados , Duodeno , Conducta Alimentaria/efectos de los fármacos , Femenino , Voluntarios Sanos , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Hambre/efectos de los fármacos , Íleon , Infusiones Parenterales , Masculino , Persona de Mediana Edad , Saciedad/efectos de los fármacos , Método Simple Ciego , Adulto Joven
4.
Eur J Nutr ; 60(6): 2923-2947, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-33559026

RESUMEN

PURPOSE: Taste receptors are expressed throughout the gastrointestinal tract. The activation of post-oral taste receptors using tastants could provide a non-invasive treatment option in combating the obesity epidemic. The aim of this review was to examine the effect of post-oral delivery of non-caloric tastants on eating behavior reflected by primary outcome energy intake and secondary outcomes GI symptoms and perceptions and potential underlying mechanisms. This review was conducted according to the PRISMA guidelines for systematic reviews. METHODS: A systematic literature search of the Cochrane, PubMed, Embase, and Medline databases was performed. This systematic review and meta-analysis was registered in the PROSPERO database on 26 February 2020 (ID: CRD42020171182). Two researchers independently screened 11,912 articles and extracted information from 19 articles. If at least two studies investigated the effect of the same taste compound on primary outcome energy intake, a meta-analysis was performed to determine pooled effect sizes. RESULTS: Nineteen papers including healthy volunteers were included. In the 19 papers analyzed, effects of various tastants were investigated in healthy volunteers. Most extensively investigated were bitter tastants. The meta-analysis of effects of bitter tastants showed a significant reduction in energy intake of 54.62 kcal (95% CI - 78.54 to - 30.69, p = 0.0014). CONCLUSIONS: Bitter stimuli are most potent to influence eating behavior. Energy intake decreased after post-oral delivery of bitter tastants. This highlights the potential of a preventive role of bitter tastants in battling the obesity epidemic.


Asunto(s)
Ingestión de Energía , Tracto Gastrointestinal , Conducta Alimentaria , Humanos , Obesidad , Gusto
5.
Crit Rev Food Sci Nutr ; 57(10): 2218-2244, 2017 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-26252442

RESUMEN

The increasing prevalence of overweight and obesity requires new, effective prevention and treatment strategies. One approach to reduce energy intake is by developing novel foods with increased satiating properties, which may be accomplished by slowing down lipolysis to deliver substrates to the ileum, thereby enhancing natural gut-brain signaling pathways of satiety that are normally induced by meal intake. To develop slow release food additives, their processing in the gastrointestinal tract has to be understood; therefore, we start from a general description of the digestive system and relate that to in vitro modeling, satiety, and lipolytic mechanisms. The effects of physicochemical lipid composition, encapsulation matrix, and interfacial structure on lipolysis are emphasized. We give an overview of techniques and materials used, and discuss partitioning, which may be a key factor for encapsulation performance. Targeted release capsules that delay lipolysis form a real challenge because of the high efficiency of the digestive system; hardly any proof was found that intact orally ingested lipids can be released in the ileum and thereby induce satiety. We expect that this challenge could be tackled with structured o/w-emulsion-based systems that have some protection against lipase, e.g., by hindering bile salt adsorption and/or delaying lipase diffusion.


Asunto(s)
Grasas de la Dieta/administración & dosificación , Digestión , Regulación hacia Abajo , Alimentos Especializados , Lipólisis , Modelos Biológicos , Sobrepeso/dietoterapia , Animales , Depresores del Apetito/administración & dosificación , Depresores del Apetito/metabolismo , Depresores del Apetito/uso terapéutico , Grasas de la Dieta/metabolismo , Grasas de la Dieta/uso terapéutico , Emulsiones , Ingestión de Energía , Aditivos Alimentarios/metabolismo , Aditivos Alimentarios/uso terapéutico , Tecnología de Alimentos/tendencias , Humanos , Absorción Intestinal , Sobrepeso/metabolismo , Respuesta de Saciedad
6.
Clin Sci (Lond) ; 130(22): 2073-2082, 2016 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-27439969

RESUMEN

Gut microbial-derived short-chain fatty acids (SCFA) are believed to affect host metabolism and cardiometabolic risk factors. The present study aim was to investigate the effects of proximal and distal colonic infusions with the SCFA acetate on fat oxidation and other metabolic parameters in men. In this randomized, double-blind crossover trial, six overweight/obese men [body mass index (BMI) 25-35 kg/m2] underwent two experimental periods: one with distal and one with proximal colonic sodium acetate infusions. A feeding catheter was endoscopically positioned at the beginning of each period and remained in the colon for three consecutive test days, enabling colonic acetate (100 or 180 mmol/l) or placebo infusion during fasting conditions and after an oral glucose load (postprandial). Fat oxidation and energy expenditure were measured using an open-circuit ventilated hood system and blood samples were repeatedly collected for 2 h during fasting and postprandial conditions. Distal colonic 180 mmol/l acetate infusions increased fasting fat oxidation (1.78±0.28 compared with -0.78±0.89 g fat 2 h-1, P=0.015), fasting peptide YY (PYY, P=0.01) and postprandial glucose and insulin concentrations (P<0.05), and tended to increase fasting plasma acetate (P=0.069) compared with placebo. Distal 100 mmol/l acetate administration tended to decrease fasting tumour necrosis factor-α (TNF-α; P=0.067) compared with placebo. In contrast, proximal colonic acetate infusions showed no effects on substrate metabolism, circulating hormones or inflammatory markers. In conclusion distal colonic acetate infusions affected whole-body substrate metabolism, with a pronounced increase in fasting fat oxidation and plasma PYY. Modulating colonic acetate may be a nutritional target to treat or prevent metabolic disorders.


Asunto(s)
Acetatos/administración & dosificación , Colon/efectos de los fármacos , Grasas/metabolismo , Obesidad/tratamiento farmacológico , Sobrepeso/tratamiento farmacológico , Adulto , Colon/metabolismo , Metabolismo Energético , Femenino , Humanos , Insulina/metabolismo , Masculino , Persona de Mediana Edad , Obesidad/metabolismo , Sobrepeso/metabolismo , Oxidación-Reducción , Péptido YY/metabolismo , Adulto Joven
7.
Theor Biol Med Model ; 11: 28, 2014 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-24917054

RESUMEN

BACKGROUND: In-silico models that attempt to capture and describe the physiological behavior of biological organisms, including humans, are intrinsically complex and time consuming to build and simulate in a computing environment. The level of detail of description incorporated in the model depends on the knowledge of the system's behavior at that level. This knowledge is gathered from the literature and/or improved by knowledge obtained from new experiments. Thus model development is an iterative developmental procedure. The objective of this paper is to describe a new plug and play scheme that offers increased flexibility and ease-of-use for modeling and simulating physiological behavior of biological organisms. METHODS: This scheme requires the modeler (user) first to supply the structure of the interacting components and experimental data in a tabular format. The behavior of the components described in a mathematical form, also provided by the modeler, is externally linked during simulation. The advantage of the plug and play scheme for modeling is that it requires less programming effort and can be quickly adapted to newer modeling requirements while also paving the way for dynamic model building. RESULTS: As an illustration, the paper models the dynamics of gastric emptying behavior experienced by humans. The flexibility to adapt the model to predict the gastric emptying behavior under varying types of nutrient infusion in the intestine (ileum) is demonstrated. The predictions were verified with a human intervention study. The error in predicting the half emptying time was found to be less than 6%. CONCLUSIONS: A new plug-and-play scheme for biological systems modeling was developed that allows changes to the modeled structure and behavior with reduced programming effort, by abstracting the biological system into a network of smaller sub-systems with independent behavior. In the new scheme, the modeling and simulation becomes an automatic machine readable and executable task.


Asunto(s)
Vaciamiento Gástrico , Modelos Biológicos , Algoritmos , Humanos , Programas Informáticos , Biología de Sistemas
8.
Gut Microbes ; 16(1): 2350173, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38738780

RESUMEN

Although fecal microbiota composition is considered to preserve relevant and representative information for distal colonic content, it is evident that it does not represent microbial communities inhabiting the small intestine. Nevertheless, studies investigating the human small intestinal microbiome and its response to dietary intervention are still scarce. The current study investigated the spatio-temporal dynamics of the small intestinal microbiome within a day and over 20 days, as well as its responses to a 14-day synbiotic or placebo control supplementation in 20 healthy subjects. Microbial composition and metabolome of luminal content of duodenum, jejunum, proximal ileum and feces differed significantly from each other. Additionally, differences in microbiota composition along the small intestine were most pronounced in the morning after overnight fasting, whereas differences in composition were not always measurable around noon or in the afternoon. Although overall small intestinal microbiota composition did not change significantly within 1 day and during 20 days, remarkable, individual-specific temporal dynamics were observed in individual subjects. In response to the synbiotic supplementation, only the microbial diversity in jejunum changed significantly. Increased metabolic activity of probiotic strains during intestinal passage, as assessed by metatranscriptome analysis, was not observed. Nevertheless, synbiotic supplementation led to a short-term spike in the relative abundance of genera included in the product in the small intestine approximately 2 hours post-ingestion. Collectively, small intestinal microbiota are highly dynamic. Ingested probiotic bacteria could lead to a transient spike in the relative abundance of corresponding genera and ASVs, suggesting their passage through the entire gastrointestinal tract. This study was registered to http://www.clinicaltrials.gov, NCT02018900.


Asunto(s)
Bacterias , Heces , Microbioma Gastrointestinal , Intestino Delgado , Simbióticos , Humanos , Simbióticos/administración & dosificación , Microbioma Gastrointestinal/fisiología , Masculino , Adulto , Intestino Delgado/microbiología , Intestino Delgado/metabolismo , Femenino , Bacterias/clasificación , Bacterias/aislamiento & purificación , Bacterias/metabolismo , Bacterias/genética , Heces/microbiología , Adulto Joven , Probióticos/administración & dosificación , Metaboloma , Voluntarios Sanos , Análisis Espacio-Temporal
9.
Regen Ther ; 27: 207-217, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38576851

RESUMEN

Background: Perinatal inflammation increases the risk for bronchopulmonary dysplasia in preterm neonates, but the underlying pathophysiological mechanisms remain largely unknown. Given their anti-inflammatory and regenerative capacity, multipotent adult progenitor cells (MAPC) are a promising cell-based therapy to prevent and/or treat the negative pulmonary consequences of perinatal inflammation in the preterm neonate. Therefore, the pathophysiology underlying adverse preterm lung outcomes following perinatal inflammation and pulmonary benefits of MAPC treatment at the interface of prenatal inflammatory and postnatal ventilation exposures were elucidated. Methods: Instrumented ovine fetuses were exposed to intra-amniotic lipopolysaccharide (LPS 5 mg) at 125 days gestation to induce adverse systemic and peripheral organ outcomes. MAPC (10 × 106 cells) or saline were administered intravenously two days post LPS exposure. Fetuses were delivered preterm five days post MAPC treatment and either killed humanely immediately or mechanically ventilated for 72 h. Results: Antenatal LPS exposure resulted in inflammation and decreased alveolar maturation in the preterm lung. Additionally, LPS-exposed ventilated lambs showed continued pulmonary inflammation and cell junction loss accompanied by pulmonary edema, ultimately resulting in higher oxygen demand. MAPC therapy modulated lung inflammation, prevented loss of epithelial and endothelial barriers and improved lung maturation in utero. These MAPC-driven improvements remained evident postnatally, and prevented concomitant pulmonary edema and functional loss. Conclusion: In conclusion, prenatal inflammation sensitizes the underdeveloped preterm lung to subsequent postnatal inflammation, resulting in injury, disturbed development and functional impairment. MAPC therapy partially prevents these changes and is therefore a promising approach for preterm infants to prevent adverse pulmonary outcomes.

10.
Anal Chem ; 85(3): 1475-83, 2013 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-23249279

RESUMEN

Histamine is a biogenic amine that is indispensable in the efficient functioning of various physiological systems. In previous work, a molecularly imprinted polymer (MIP) based sensor platform with impedimetric read-out was presented which could rapidly and at low cost determine histamine concentrations in buffer solutions within pH 7-9. For diagnostic applications, histamine should be detectable in a wider pH range as it mostly occurs in mildly acidic environments. To understand this pH-dependent response of the MIP sensor, we propose a statistical binding analysis model. Within this model, we predict the theoretical performance of MIP based on acrylic acid in the required pH range and verify these results experimentally by UV-vis spectroscopy, microgravimetry, and impedance spectroscopy. Using impedimetric read-out, specific and selective detection of histamine in the physiologically relevant nanomolar concentration range is possible in neutral and mildly acidic phosphate buffer. Finally, this sensor platform was used to analyze the histamine concentration of mildly acidic bowel fluid samples of several test persons. We show that this sensor provides reliable data in the relevant concentration regime, which was validated independently by enzyme-linked immuno sorbent assay (ELISA) tests.


Asunto(s)
Líquidos Corporales/metabolismo , Espectroscopía Dieléctrica/métodos , Duodeno/metabolismo , Histamina/metabolismo , Receptores Artificiales/metabolismo , Sitios de Unión/fisiología , Humanos , Concentración de Iones de Hidrógeno
11.
Nutrients ; 15(4)2023 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-36839304

RESUMEN

BACKGROUND: Dietary fibers are subjected to saccharolytic fermentation by the gut microbiota, leading to the production of short chain fatty acids (SCFAs). SCFAs act as signaling molecules to different cells in the human body including skeletal muscle cells. The ability of SCFAs to induce multiple signaling pathways, involving nuclear erythroid 2-related factor 2 (Nrf2), may contribute to the redox balance, and thereby may be involved in glucose homeostasis. The aim of this study is to investigate whether SCFAs increase glucose uptake by upregulating the endogenous antioxidant glutathione (GSH) in C2C12 myotubes. METHODS: C2C12 myotubes were exposed to 1, 5, or 20 mM of single (acetate, propionate, or butyrate) or mixtures of SCFAs for 24 h. Cytotoxicity, glucose uptake, and intracellular GSH levels were measured. RESULTS: 20 mM of mixture but not separate SCFAs induced cytotoxicity. Exposure to a mixture of SCFAs at 5 mM increased glucose uptake in myotubes, while 20 mM of propionate, butyrate, and mixtures decreased glucose uptake. Exposure to single SCFAs increased GSH levels in myotubes; however, SCFAs did not prevent the menadione-induced decrease in glucose uptake in myotubes. CONCLUSIONS: The effect of SCFAs on modulating glucose uptake in myotubes is not associated with the effect on endogenous GSH levels.


Asunto(s)
Butiratos , Propionatos , Humanos , Propionatos/metabolismo , Butiratos/farmacología , Ácidos Grasos Volátiles/metabolismo , Acetatos , Fibras Musculares Esqueléticas/metabolismo , Glucosa/metabolismo
12.
Microbiome ; 11(1): 43, 2023 03 07.
Artículo en Inglés | MEDLINE | ID: mdl-36879297

RESUMEN

BACKGROUND: The effects of fermented food consumption on the small intestine microbiome and its role on host homeostasis are largely uncharacterised as our knowledge on intestinal microbiota relies mainly on faecal samples analysis. We investigated changes in small intestinal microbial composition and functionality, short chain fatty acid (SCFA) profiles, and on gastro-intestinal (GI) permeability in ileostomy subjects upon the consumption of fermented milk products. RESULTS: We report the results from a randomised, cross-over, explorative study where 16 ileostomy subjects underwent 3, 2-week intervention periods. In each period, they consumed either milk fermented by Lacticaseibacillus rhamnosus CNCM I-3690, or milk fermented by Streptococcus thermophilus CNCM I-1630 and Lactobacillus delbrueckii subsp. bulgaricus CNCM I-1519, or a chemically acidified milk (placebo) daily. We performed metataxonomic, metatranscriptomic analysis, and SCFA profiling of ileostomy effluents as well as a sugar permeability test to investigate the microbiome impact of these interventions and their potential effect on mucosal barrier function. Consumption of the intervention products impacted the overall small intestinal microbiome composition and functionality, mainly due to the introduction of the product-derived bacteria that reach in several samples 50% of the total microbial community. The interventions did not affect the SCFA levels in ileostoma effluent, or gastro-intestinal permeability and the effects on the endogenous microbial community were negligible. The impact on microbiome composition was highly personalised, and we identified the poorly characterised bacterial family, Peptostreptococcaceae, to be positively associated with a low abundance of the ingested bacteria. Activity profiling of the microbiota revealed that carbon- versus amino acid-derived energy metabolism of the endogenous microbiome could be responsible for the individual-specific intervention effects on the small intestine microbiome composition and function, reflected also on urine microbial metabolites generated through proteolytic fermentation. CONCLUSIONS: The ingested bacteria are the main drivers of the intervention effect on the small intestinal microbiota composition. Their transient abundance level is highly personalised and influenced by the energy metabolism of the ecosystem that is reflected by its microbial composition ( http://www. CLINICALTRIALS: gov , ID NCT NCT02920294). Video Abstract.


Asunto(s)
Líquidos Corporales , Productos Lácteos Cultivados , Microbioma Gastrointestinal , Microbiota , Humanos , Bacterias/genética
13.
Gut Microbes ; 15(1): 2244720, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37589280

RESUMEN

Fermented foods and beverages are a significant source of dietary bacteria that enter the gastrointestinal (GI) tract. However, little is known about how these microbes survive and adapt to the small intestinal environment. Colony-forming units (CFU) enumeration and viability qPCR of Lacticaseibacillus rhamnosus CNCM I-3690 in the ileal effluent of 10 ileostomy subjects during 12-h post consumption of a dairy product fermented with this strain demonstrated the high level of survival of this strain during human small intestine passage. Metatranscriptome analyses revealed the in situ transcriptome of L. rhamnosus in the small intestine, which was contrasted with transcriptome data obtained from in vitro cultivation. These comparative analyses revealed substantial metabolic adaptations of L. rhamnosus during small intestine transit, including adjustments of carbohydrate metabolism, surface-protein expression, and translation machinery. The prominent presence of L. rhamnosus in the effluent samples did not elicit an appreciable effect on the composition of the endogenous small intestine microbiome, but significantly altered the ecosystem's overall activity profile, particularly of pathways associated with carbohydrate metabolism. Strikingly, two of the previously recognized gut-brain metabolic modules expressed in situ by L. rhamnosus (inositol degradation and glutamate synthesis II) are among the most dominantly enriched activities in the ecosystem's activity profile. This study establishes the survival capacity of L. rhamnosus in the human small intestine and highlights its functional adjustment in situ, which we postulate to play a role in the probiotic effects associated with this strain.


Asunto(s)
Microbioma Gastrointestinal , Lacticaseibacillus rhamnosus , Microbiota , Probióticos , Humanos , Íleon
14.
Front Nutr ; 10: 1245355, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38089924

RESUMEN

Background and aims: Observational data indicate that diets rich in fruits and vegetables have a positive effect on inflammatory status, improve metabolic resilience and may protect against the development of non-communicable diseases. Nevertheless, experimental evidence demonstrating a causal relationship between nutrient intake (especially whole foods) and changes in metabolic health is scarce. This study investigated the pleiotropic effects of sulforaphane from broccoli sprouts, compared to pea sprouts, on biomarkers of endothelial function, inflammation and metabolic stress in healthy participants subjected to a standardized caloric challenge. Methods: In this double-blind, crossover, randomized, placebo-controlled trial 12 healthy participants were administered 16 g broccoli sprouts, or pea sprouts (placebo) followed by the standardized high-caloric drink PhenFlex given to disturb healthy homeostasis. Levels of inflammatory biomarkers and metabolic parameters were measured in plasma before and 2 h after the caloric overload. Results: Administration of broccoli sprouts promoted an increase in levels of CCL-2 induced by caloric load (p = 0.017). Other biomarkers (sICAM-1, sVCAM-1, hs-CRP, and IL-10) individually showed insignificant tendencies toward increase with administration of sulforaphane. Combining all studied biomarkers into the systemic low-grade inflammation score further confirmed upregulation of the inflammatory activity (p = 0.087) after sulforaphane. No significant effects on biomarkers of metabolic stress were detected. Conclusion: This study has demonstrated that sulforaphane facilitated development of a mild pro-inflammatory state during the caloric challenge, which could be suggestive of the onset of the hormetic response induced by this phytonutrient. The use of integrative outcomes measures such as the systemic low-grade inflammation score can be viewed as a more robust approach to study the subtle and pleiotropic effects of phytonutrients.Clinical trial registration:www.clinicaltrials.gov, identifier NCT05146804.

15.
Front Nutr ; 10: 1204561, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37485383

RESUMEN

Background and aims: As our understanding of platelet activation in response to infections and/or inflammatory conditions is growing, it is becoming clearer that safe, yet efficacious, platelet-targeted phytochemicals could improve public health beyond the field of cardiovascular diseases. The phytonutrient sulforaphane shows promise for clinical use due to its effect on inflammatory pathways, favorable pharmacokinetic profile, and high bioavailability. The potential of sulforaphane to improve platelet functionality in impaired metabolic processes has however hardly been studied in humans. This study investigated the effects of broccoli sprout consumption, as a source of sulforaphane, on urinary 11-dehydro-thromboxane B2 (TXB2), a stable thromboxane metabolite used to monitor eicosanoid biosynthesis and response to antithrombotic therapy, in healthy participants exposed to caloric overload. Methods: In this double-blind, placebo-controlled, crossover trial 12 healthy participants were administered 16g of broccoli sprouts, or pea sprouts (placebo) followed by the standardized high-caloric drink PhenFlex given to challenge healthy homeostasis. Urine samples were collected during the study visits and analyzed for 11-dehydro-TXB2, sulforaphane and its metabolites. Genotyping was performed using Illumina GSA v3.0 DTCBooster. Results: Administration of broccoli sprouts before the caloric load reduced urinary 11-dehydro-TXB2 levels by 50% (p = 0.018). The amount of sulforaphane excreted in the urine during the study visits correlated negatively with 11-dehydro-TXB2 (rs = -0.377, p = 0.025). Participants carrying the polymorphic variant NAD(P)H dehydrogenase quinone 1 (NQO1*2) showed decreased excretion of sulforaphane (p = 0.035). Conclusion: Sulforaphane was shown to be effective in targeting platelet responsiveness after a single intake. Our results indicate an inverse causal relationship between sulforaphane and 11-dehydro-TXB2, which is unaffected by the concomitant intake of the metabolic challenge. 11-Dehydro-TXB2 shows promise as a non-invasive, sensitive, and suitable biomarker to investigate the effects of phytonutrients on platelet aggregation within hours. Clinical trial registration: [https://clinicaltrials.gov/], identifier [NCT05146804].

16.
Proc Natl Acad Sci U S A ; 106(7): 2371-6, 2009 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-19190178

RESUMEN

How do we acquire immune tolerance against food microorganisms and commensal bacteria that constitute the intestinal microbiota? We investigated this by stimulating the immune system of adults with commensal Lactobacillus plantarum bacteria. We studied the in vivo human responses to L. plantarum in a randomized double-blind placebo-controlled cross-over study. Healthy adults ingested preparations of living and heat-killed L. plantarum bacteria. Biopsies were taken from the intestinal duodenal mucosa and altered expression profiles were analyzed using whole-genome microarrays and by biological pathway reconstructions. Expression profiles of human mucosa displayed striking differences in modulation of NF-kappaB-dependent pathways, notably after consumption of living L. plantarum bacteria in different growth phases. Our in vivo study identified mucosal gene expression patterns and cellular pathways that correlated with the establishment of immune tolerance in healthy adults.


Asunto(s)
Duodeno/microbiología , Perfilación de la Expresión Génica , Regulación Bacteriana de la Expresión Génica , Sistema Inmunológico , Lactobacillus plantarum/metabolismo , FN-kappa B/metabolismo , Adulto , Método Doble Ciego , Humanos , Tolerancia Inmunológica , Modelos Biológicos , Placebos , Reacción en Cadena de la Polimerasa , Transcripción Genética
17.
Nutrients ; 14(14)2022 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-35889917

RESUMEN

The regulation of blood flow to peripheral muscles is crucial for proper skeletal muscle functioning and exercise performance. During exercise, increased mitochondrial oxidative phosphorylation leads to increased electron leakage and consequently induces an increase in ROS formation, contributing to DNA, lipid, and protein damage. Moreover, exercise may increase blood- and intramuscular inflammatory factors leading to a deterioration in endurance performance. The aim of this review is to investigate the potential mechanisms through which the polyphenol hesperidin could lead to enhanced exercise performance, namely improved endothelial function, reduced exercise-induced oxidative stress, and inflammation. We selected in vivo RCTs, animal studies, and in vitro studies in which hesperidin, its aglycone form hesperetin, hesperetin-metabolites, or orange juice are supplemented at any dosage and where the parameters related to endothelial function, oxidative stress, and/or inflammation have been measured. The results collected in this review show that hesperidin improves endothelial function (via increased NO availability), inhibits ROS production, decreases production and plasma levels of pro-inflammatory markers, and improves anaerobic exercise outcomes (e.g., power, speed, energy). For elite and recreational athletes, hesperidin could be used as an ergogenic aid to enhance muscle recovery between training sessions, optimize oxygen and nutrient supplies to the muscles, and improve anaerobic performance.


Asunto(s)
Hesperidina , Sustancias para Mejorar el Rendimiento , Animales , Antioxidantes/farmacología , Hesperidina/metabolismo , Hesperidina/farmacología , Humanos , Inflamación , Estrés Oxidativo , Sustancias para Mejorar el Rendimiento/farmacología , Especies Reactivas de Oxígeno/metabolismo
18.
Food Chem ; 129(3): 731-8, 2011 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-25212292

RESUMEN

Recent studies have found different types of taste receptors located along the intestine. However, the effect of tastants, and in particular sweet tastants, on satiety hormone release is still unknown. STC-1 cells were incubated with different concentrations of bitter, sour, sweet, salty, and umami tastants. After incubation with different time-periods, cholecystokinin (CCK) and glucagons-like peptide 1 (GLP-1) concentrations were measured in the supernatant. All tastants increased the CCK levels both dose- and time-dependently. GLP-1 release dose-dependently increased after the addition of all tastants, with the exception of acetic acid. GLP-1 was released in a time-dependent manner after the addition of all tastants, but bitter tastants stimulated GLP-1 release only during the first 15min of exposure. All commercial sweeteners elevated CCK and GLP-1 levels, with Tagatesse exerting the strongest effects. Tastants, and in particular sweet, play a role in the regulation of satiety hormone release, both in a concentration- and time-dependent manner.

19.
J Int Soc Sports Nutr ; 18(1): 2, 2021 Jan 06.
Artículo en Inglés | MEDLINE | ID: mdl-33407631

RESUMEN

BACKGROUND: Nutritional supplementation is commonly used by athletes to improve their exercise performance. Previous studies demonstrated that citrus flavonoid extract (CFE) supplementation may be an effective strategy to improve exercise performance in male athletes. Yet, no conclusive research has been performed to investigate the effect of chronic CFE supplementation on high-intensity exercise performance under anaerobic conditions. Therefore, the aim of the study was to assess whether CFE supplementation in daily dosages of 400 and 500 mg for a period of 4 and 8 weeks improves anaerobic exercise capacity. METHODS: A randomized, double-blind, placebo controlled, parallel clinical study was conducted in 92 moderately trained healthy men and women. Subjects were randomized to receive 400 mg of CFE (n = 30), 500 mg of CFE (n = 31) or placebo (n = 31) daily, for 8 consecutive weeks. The Wingate anaerobic test was used to assess anaerobic exercise capacity and power output at baseline, after 4 weeks and after 8 weeks. RESULTS: After 4 weeks supplementation, average power output significantly increased in the 400 mg group (Estimated difference [ED] = 38.2 W [18.0, 58.3]; p < 0.001; effect size [ES] = 0.27) and in the 500 mg group (ED = 21.2 W [0.91, 41.4]; p = 0.041; ES = 0.15) compared to placebo. The 5 s peak power output was also increased in the 400 mg group (ED = 53.6 [9.96, 97.2]; p = 0.017; ES = 0.25) after 4 weeks compared to placebo. After 8 weeks of supplementation, average power output was significantly improved in the group receiving 400 mg of CFE (ED = 31.6 [8.33, 54.8]; p = 0.008; ES = 0.22) compared to placebo. CONCLUSION: These results demonstrate that CFE supplementation improved anaerobic capacity and peak power during high intensity exercise in moderately trained individuals. Further research is needed to identify the underlying mechanisms that are affected by CFE supplementation. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT03044444 ). Registered 7 February 2017.


Asunto(s)
Anaerobiosis/efectos de los fármacos , Citrus/química , Suplementos Dietéticos , Flavonoides/farmacología , Resistencia Física/efectos de los fármacos , Extractos Vegetales/farmacología , Adulto , Anaerobiosis/fisiología , Atletas , Método Doble Ciego , Ejercicio Físico/fisiología , Femenino , Flavonoides/administración & dosificación , Hesperidina/administración & dosificación , Hesperidina/farmacología , Humanos , Masculino , Consumo de Oxígeno/fisiología , Resistencia Física/fisiología , Placebos/administración & dosificación , Extractos Vegetales/administración & dosificación , Fenómenos Fisiológicos en la Nutrición Deportiva , Factores de Tiempo , Adulto Joven
20.
Am J Clin Nutr ; 114(3): 843-861, 2021 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-34036315

RESUMEN

Intestinal catheters have been used for decades in human nutrition, physiology, pharmacokinetics, and gut microbiome research, facilitating the delivery of compounds directly into the intestinal lumen or the aspiration of intestinal fluids in human subjects. Such research provides insights about (local) dynamic metabolic and other intestinal luminal processes, but working with catheters might pose challenges to biomedical researchers and clinicians. Here, we provide an overview of practical and technical aspects of applying naso- and oro-intestinal catheters for delivery of compounds and sampling luminal fluids from the jejunum, ileum, and colon in vivo. The recent literature was extensively reviewed, and combined with experiences and insights we gained through our own clinical trials. We included 60 studies that involved a total of 720 healthy subjects and 42 patients. Most of the studies investigated multiple intestinal regions (24 studies), followed by studies investigating only the jejunum (21 studies), ileum (13 studies), or colon (2 studies). The ileum and colon used to be relatively inaccessible regions in vivo. Custom-made state-of-the-art catheters are available with numerous options for the design, such as multiple lumina, side holes, and inflatable balloons for catheter progression or isolation of intestinal segments. These allow for multiple controlled sampling and compound delivery options in different intestinal regions. Intestinal catheters were often used for delivery (23 studies), sampling (10 studies), or both (27 studies). Sampling speed decreased with increasing distance from the sampling syringe to the specific intestinal segment (i.e., speed highest in duodenum, lowest in ileum/colon). No serious adverse events were reported in the literature, and a dropout rate of around 10% was found for these types of studies. This review is highly relevant for researchers who are active in various research areas and want to expand their research with the use of intestinal catheters in humans in vivo.


Asunto(s)
Cateterismo/métodos , Intestinos/fisiología , Proyectos de Investigación , Cateterismo/instrumentación , Humanos
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