Antenatal Ureaplasma Infection Causes Colonic Mucus Barrier Defects: Implications for Intestinal Pathologies.

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.

The Interplay Between Stress and Fullness in Patients With Functional Dyspepsia and Healthy Controls: An Exploratory Experience Sampling Method Study.

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.

Effect of oral or intragastric delivery of the bitter tastant quinine on food intake and appetite sensations: a randomised crossover trial.

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.

Effects of gastrointestinal delivery of non-caloric tastants on energy intake: a systematic review and meta-analysis.

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.

Food-grade micro-encapsulation systems that may induce satiety via delayed lipolysis: A review.

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.

Distal, not proximal, colonic acetate infusions promote fat oxidation and improve metabolic markers in overweight/obese men.

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.

A new flexible plug and play scheme for modeling, simulating, and predicting gastric emptying.

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.

Detection of gluten peptides in human duodenal fluids with immuno-liquid chromatography-mass spectrometry.

Gluten proteins are storage proteins in wheat that exhibit a certain resistance to gastrointestinal digestion. To explore solutions to cope with accidental ingestion of gluten in individuals suffering from gluten-related disorders, it is essential to monitor the fate of gluten peptides in biological samples, i.e., gastrointestinal juices, blood plasma or urine. In this work, we aimed at developing a mass spectrometry (MS)-based method for measuring gluten peptides in human duodenal fluids. Seven gluten peptides, including the well-documented 33-mer gluten peptide (LQLQPFPQPQLPYPQPQLPYPQPQLPYPQPQPF), were selected after a literature review and characterization of a gluten-containing product. Isotopically labelled peptides were used as references and a targeted liquid chromatography (LC) MS assay based on high resolution parallel reaction monitoring (PRM) was designed. Despite iterative and fine tuning of the LC-PRM-MS method, the low level of endogenous gluten peptides in human duodenal fluid samples precluded their direct detection. Thus, an initial immunoprecipitation (IP) step was included. Several antibodies were tested, and one proved reliable for the enrichment of the 33-mer gluten peptide as well as a few additional gluten peptides. Figures-of-merits of the immuno-LC-PRM-MS assay were assessed with a focus on quantification trueness and precision. We have developed an MS-based method for measuring the 33-mer gluten peptide in human duodenal fluids. Based on isotopic dilution, the method relies on the combination of IP and LC-PRM-MS analysis. Measurements were shown to be sensitive, quantitative, and reproducible.

Hesperetin but not ellagic acid increases myosin heavy chain expression and cell fusion in C2C12 myoblasts in the presence of oxidative stress.

Introduction: Skeletal muscle regeneration is impaired in elderly. An oxidative stress-induced decrease in differentiation capacity of muscle satellite cells is a key factor in this process. The aim of this study is to investigate whether orange polyphenol hesperetin and pomegranate polyphenol ellagic acid enhance myoblast differentiation in the presence and absence of oxidative stress, and to explore underlying mechanisms. Methods: C2C12 myoblasts were proliferated for 24 h and differentiated for 120 h while exposed to hesperetin (5, 20, 50 µM), ellagic acid (0.05, 0.1 µM) or a combination (20 µM hesperetin, 0.05 µM ellagic acid) with and without oxidative stress-inducing compound menadione (9 µM) during 24 h of proliferation and during the first 5 h of differentiation. The number of proliferating cells was assessed using fluorescent labeling of incorporated 5-ethynyl-2'-deoxyuridine. Myosin heavy chain expression was assessed by fluorescence microscopy and cell fusion index was calculated. Furthermore, protein expression of phosphorylated p38 and myomixer were assessed using Western blot. Results: None of the compounds induced effects on cell proliferation. Without menadione, 50 µM hesperetin increased fusion index by 12.6% compared to control (p < 0.01), while ellagic acid did not affect measured parameters of differentiation. Menadione treatment did not change myosin heavy chain expression and fusion index. In combination with menadione, 20 µM hesperetin increased myosin heavy chain expression by 35% (p < 0.01) and fusion index by 7% (p = 0.04) compared to menadione. Furthermore, the combination of menadione with hesperetin and ellagic acid increased myosin heavy chain expression by 35% compared to menadione (p = 0.02). Hesperetin and ellagic acid did not change p38 phosphorylation and myomixer expression compared to control, while treatment with menadione increased p38 phosphorylation (p < 0.01) after 5 h and decreased myomixer expression (p = 0.04) after 72 h of differentiation. Conclusion and discussion: Hesperetin increased myosin heavy chain expression in the presence of oxidative stress induced by menadione, and increased cell fusion both in the presence and absence of menadione. Ellagic acid did not affect the measured parameters of myoblast differentiation. Therefore, hesperetin should be considered as nutritional prevention or treatment strategy to maintain muscle function in age-related diseases such as sarcopenia. Future research should focus on underlying mechanisms and translation of these results to clinical practice.

Spatio-temporal dynamics of the human small intestinal microbiome and its response to a synbiotic.

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.

Multipotent adult progenitor cells prevent functional impairment and improve development in inflammation driven detriment of preterm ovine lungs.

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.

Impedimetric detection of histamine in bowel fluids using synthetic receptors with pH-optimized binding characteristics.

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.

A Combination of Acetate, Propionate, and Butyrate Increases Glucose Uptake in C2C12 Myotubes.

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.

L. rhamnosus CNCM I-3690 survival, adaptation, and small bowel microbiome impact in human.

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.

Sulforaphane as a potential modifier of calorie-induced inflammation: a double-blind, placebo-controlled, crossover trial.

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.

Endogenous small intestinal microbiome determinants of transient colonisation efficiency by bacteria from fermented dairy products: a randomised controlled trial.

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.

The beneficial effect of sulforaphane on platelet responsiveness during caloric load: a single-intake, double-blind, placebo-controlled, crossover trial in healthy participants.

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].

Differential NF-kappaB pathways induction by Lactobacillus plantarum in the duodenum of healthy humans correlating with immune tolerance.

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.

Hesperidin Functions as an Ergogenic Aid by Increasing Endothelial Function and Decreasing Exercise-Induced Oxidative Stress and Inflammation, Thereby Contributing to Improved Exercise Performance.

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.

Different tastants and low-caloric sweeteners induce differential effects on the release of satiety hormones.

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.