BACKGROUND: Exclusive enteral nutrition (EEN) is an effective treatment for active Crohn's disease (CD). This study explored the immunostimulatory potential of a cell-free fecal filtrate and related this with changes in the fecal microbiota and metabolites in children with active CD undertaking treatment with EEN. METHODS: Production of tumor necrosis factor α (TNFα) from peripheral blood mononuclear cells was measured following their stimulation with cell-free fecal slurries from children with CD, before, during, and at completion of EEN. The metabolomic profile of the feces used was quantified using proton nuclear magnetic resonance and their microbiota composition with 16S ribosomal RNA sequencing. RESULTS: Following treatment with EEN, 8 (72%) of 11 patients demonstrated a reduction in fecal calprotectin (FC) >50% and were subsequently labeled FC responders. In this subgroup, TNFα production from peripheral blood mononuclear cells was reduced during EEN (P = .008) and reached levels like healthy control subjects. In parallel to these changes, the fecal concentrations of acetate, butyrate, propionate, choline, and uracil significantly decreased in FC responders, and p-cresol significantly increased. At EEN completion, TNFα production from peripheral blood mononuclear cells was positively correlated with butyrate (rho = 0.70; P = .016). Microbiota structure (β diversity) was influenced by EEN treatment, and a total of 28 microbial taxa changed significantly in fecal calprotectin responders. At EEN completion, TNFα production positively correlated with the abundance of fiber fermenters from Lachnospiraceae_UCG-004 and Faecalibacterium prausnitzii and negatively with Hungatella and Eisenbergiella tayi. CONCLUSIONS: This study offers proof-of concept data to suggest that the efficacy of EEN may result from modulation of diet-dependent microbes and their products that cause inflammation in patients with CD.
- MeSH
- Crohnova nemoc * terapie mikrobiologie imunologie MeSH
- dítě MeSH
- enterální výživa * metody MeSH
- feces * mikrobiologie chemie MeSH
- leukocytární L1-antigenní komplex * analýza MeSH
- leukocyty mononukleární imunologie metabolismus MeSH
- lidé MeSH
- mladiství MeSH
- střevní mikroflóra * MeSH
- TNF-alfa * metabolismus MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Five putrescine and spermidine derivatives (1-5) together with five rotenoids (6-10) were isolated from a methanolic extract of the flowers of A. fruticosa that displayed promising inhibition of 76.0 ± 1.9% for AChE and 90.0 ± 4.0% for BuChE at a concentration of 1 mg/mL. Although the anticholinesterase activities of the isolated compounds did not reach that of galantamine, molecular docking revealed that all-trans-tri-p-coumaroylspermidine and trans-trans-cis-tri-p-coumaroylspermidine showed binding poses mimicking the known inhibitor galantamine and thus could serve as model molecules in future searches for new AChE and BuChE inhibitors.
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Predicting response to exclusive enteral nutrition (EEN) in active Crohn's disease (CD) could lead to therapy personalization and pretreatment optimization. OBJECTIVES: This study aimed to explore the ability of pretreatment parameters to predict fecal calprotectin (FCal) levels at EEN completion in a prospective study in children with CD. METHODS: In children with active CD, clinical parameters, dietary intake, cytokines, inflammation-related blood proteomics, and diet-related metabolites, metabolomics and microbiota in feces, were measured before initiation of 8 wk of EEN. Prediction of FCal levels at EEN completion was performed using machine learning. Data are presented with medians (IQR). RESULTS: Of 37 patients recruited, 15 responded (FCal < 250 μg/g) to EEN (responders) and 22 did not (nonresponders). Clinical and immunological parameters were not associated with response to EEN. Responders had lesser (μmol/g) butyrate [responders: 13.2 (8.63-18.4) compared with nonresponders: 22.3 (12.0-32.0); P = 0.03], acetate [responders: 49.9 (46.4-68.4) compared with nonresponders: 70.4 (57.0-95.5); P = 0.027], phenylacetate [responders: 0.175 (0.013-0.611) compared with nonresponders: 0.943 (0.438-1.35); P = 0.021], and a higher microbiota richness [315 (269-347) compared with nonresponders: 243 (205-297); P = 0.015] in feces than nonresponders. Responders consumed (portions/1000 kcal/d) more confectionery products [responders: 0.55 (0.38-0.72) compared with nonresponders: 0.19 (0.01-0.38); P = 0.045]. A multicomponent model using fecal parameters, dietary data, and clinical and immunological parameters predicted response to EEN with 78% accuracy (sensitivity: 80%; specificity: 77%; positive predictive value: 71%; negative predictive value: 85%). Higher taxon abundance from Ruminococcaceae, Lachnospiraceae, and Bacteroides and phenylacetate, butyrate, and acetate were the most influential variables in predicting lack of response to EEN. CONCLUSIONS: We identify microbial signals and diet-related metabolites in feces, which could comprise targets for pretreatment optimization and personalized nutritional therapy in pediatric CD.
- MeSH
- acetáty MeSH
- butyráty MeSH
- Crohnova nemoc * terapie metabolismus MeSH
- dítě MeSH
- enterální výživa MeSH
- fenylacetáty MeSH
- indukce remise MeSH
- lidé MeSH
- metabolom MeSH
- mikrobiota * MeSH
- prospektivní studie MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
AIMS/HYPOTHESIS: We previously detected indications that beta cell function is protected by gluten-free diet (GFD) introduced shortly after the onset of childhood type 1 diabetes. The present aim was to assess whether GFD was associated with changes in the gut bacteriome composition and in its functional capacity, and whether such changes mediated the observed effects of GFD on beta cell function. METHODS: Forty-five children (aged 10.2 ± 3.3 years) were recruited into a self-selected intervention trial primarily focused on determining the role of GFD on beta cell preservation ( ClinicalTrials.gov NCT02867436). Stool samples were collected prior to the dietary intervention and then at 3-month intervals. A total of 128 samples from the GFD group and 112 from the control group were analysed for bacteriome 16S rDNA community profiles, the bacteriome functional capacity was predicted using PICRUSt2 and actual gut metabolome profiles measured using NMR. Intestinal permeability was assessed using serum zonulin concentrations at 1, 6 and 12 months and lactulose/mannitol tests at the end of intervention. Dietary questionnaires were used to ensure that the dietary intervention did not result in differences in energy or nutrient intake. RESULTS: The bacteriome community composition changed during the intervention with GFD: of abundant genera, a 3.3-fold decrease was noted for Bifidobacterium genus (adjusted p=1.4 × 10-4 in a DESeq2 model, p=0.026 in generalised estimating equations model), whereas a 2.4-fold increase was observed in Roseburia (adjusted p=0.02 in DESeq2 model, p=0.002 in generalised estimating equations model). The within-sample (alpha) diversity did not change, and there was no statistically significant clustering of GFD samples in the ordination graphs of beta diversity. Neither of the genera changes upon GFD intervention showed any association with the pace of beta cell loss (p>0.50), but of the remaining taxa, several genera of Bacteroidaceae family yielded suggestive signals. The faecal metabolome profile ordination correlated with that of bacteriomes but did not associate with GFD or categories of beta cell preservation. There was no indication of changes in gut permeability. CONCLUSIONS/INTERPRETATION: The bacteriome reacted to GFD, but the changes were unrelated to the pace of beta cell capacity loss. The previously observed moderately protective effect of GFD is therefore mediated through other pathways.
Within the group of higher fungi, edible medicinal mushrooms have a long history of being used as food and in folk medicine. These species contain biologically active substances with many potential beneficial effects on human health. The Pleurotus genus is representative of medicinal mushrooms because Pleurotus ostreatus is one of the most commonly cultivated culinary mushrooms. In our study, we focused on lesser-known species in the genus Pleurotus and measured their antioxidant and anti-inflammatory activity. We prepared extracts of the mushrooms and analyzed them using HPLC-HRMS, GC-MS, and 1H-NMR. Significant differences in biological activities were found among the Pleurotus spp. extracts. A MeOH extract of P. flabellatus was the most active as a radical scavenger with the highest ORAC, while a chloroform extract had significant anti-inflammatory COX-2 activity. The 80% MeOH extract of P. flabellatus contained the highest amounts of ergosterol, ergothioneine, and mannitol. The 80% MeOH extract of P. ostreatus Florida was the most active in the NF-κB inhibition assay and had the highest content of β-glucans (43.3% by dry weight). Given the antioxidant and anti-inflammatory properties of P. flabellatus, the potential therapeutic usefulness of this species is worth evaluating through in-depth investigations and confirmation by clinical trials.
- Publikační typ
- časopisecké články MeSH
