| 1. |
- Ahluwalia, Bani, et al.
(författare)
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Differences in Metabolite Composition of Aloe barbadensis Mill. Extracts Lead to Differential Effects on Human Blood T Cell Activity In Vitro
- 2022
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Ingår i: Molecules. - : MDPI AG. - 1420-3049 .- 1420-3049. ; 27:19
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Tidskriftsartikel (refereegranskat)abstract
- Aloe barbadensis Mill. (Aloe) is used for diverse therapeutic properties including immunomodulation. However, owing to the compositionally complex nature of Aloe, bioactive component(s) responsible for its beneficial properties, though thought to be attributed to polysaccharides (acemannan), remain unknown. We therefore aimed to determine the metabolite composition of various commercial Aloe extracts and assess their effects on human blood T cell activity in vitro. Peripheral blood mononuclear cells (PBMC) from healthy donors were stimulated polyclonally in presence or absence of various Aloe extracts. T cell phenotype and proliferation were investigated by flow cytometry. Aloe extracts were analyzed using targeted 1H-NMR spectroscopy for standard phytochemical quality characterization and untargeted gas chromatography mass spectrometry (GC-MS) for metabolite profiling. Aloe extracts differing in their standard phytochemical composition had varying effects on T cell activation, proliferation, apoptosis, and cell-death in vitro, although this was not related to the acemannan content. Furthermore, each Aloe extract had its own distinct metabolite profile, where extracts rich in diverse sugar and sugar-derivatives were associated with reduced T cell activity. Our results demonstrate that all commercial Aloe extracts are unique with distinct metabolite profiles, which lead to differential effects on T cell activity in vitro, independent of the acemannan content.
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| 2. |
- Hallingström, Maria, et al.
(författare)
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Metabolomic profiles of mid-trimester amniotic fluid are not associated with subsequent spontaneous preterm delivery or gestational duration at delivery
- 2022
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Ingår i: Journal of Maternal-Fetal and Neonatal Medicine. - : Informa UK Limited. - 1476-7058 .- 1476-4954. ; 35:11, s. 2054-2062
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Tidskriftsartikel (refereegranskat)abstract
- Introduction:Spontaneous preterm delivery (<37 gestational weeks) has a multifactorial etiology with still incompletely identified pathways. Amniotic fluid is a biofluid with great potential for insights into the feto-maternal milieu. It is rich in metabolites, and metabolic consequences of inflammation is yet researched only to a limited extent. Metabolomic profiling provides opportunities to identify potential biomarkers of inflammatory conditioned pregnancy complications such as spontaneous preterm delivery. Objective:The aim of this study was to perform metabolomic profiling of amniotic fluid from uncomplicated singleton pregnancies in the mid-trimester to identify potential biomarkers associated with spontaneous preterm delivery and gestational duration at delivery. A secondary aim was to replicate previously reported mid-trimester amniotic fluid metabolic biomarkers of spontaneous preterm delivery in asymptomatic women. Method:A nested case-control study was performed within a larger cohort study of asymptomatic pregnant women undergoing mid-trimester genetic amniocentesis at 14-19 gestational weeks in Gothenburg, Sweden. Medical records were used to obtain clinical data and delivery outcome variables. Amniotic fluid samples from women with a subsequent spontaneous preterm delivery (n = 37) were matched with amniotic fluid samples from women with a subsequent spontaneous delivery at term (n = 37). Amniotic fluid samples underwent untargeted metabolomic analyses using liquid chromatography-mass spectrometry. Multivariate random forest analyses were used for data processing. A secondary targeted analysis was performed, aiming to replicate previously reported mid-trimester amniotic fluid metabolic biomarkers in women with a subsequent spontaneous preterm delivery. Results:Multivariate analysis did not distinguish the samples from women with a subsequent spontaneous preterm delivery from those with a subsequent term delivery. Neither was the metabolic profile associated with gestational duration at delivery. Potential metabolic biomarker candidates were identified from four publications by two different research groups relating mid-trimester amniotic fluid metabolomes to spontaneous PTD, of which fifteen markers were included in the secondary analysis. None of these were replicated. Conclusions:Metabolomic profiles of early mid-trimester amniotic fluid were not associated with spontaneous preterm delivery or gestational duration at delivery in this cohort.
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| 3. |
- Hartvigsson, Olle, 1991, et al.
(författare)
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Differences between Arterial and Venous Umbilical Cord Plasma Metabolome and Association with Parity
- 2022
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Ingår i: Metabolites. - : MDPI AG. - 2218-1989 .- 2218-1989. ; 12:2
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Tidskriftsartikel (refereegranskat)abstract
- Umbilical cord blood is frequently used in health monitoring of the neonate. Results may be affected by the proportion of arterial and venous cord blood, the venous blood coming from the mother to supply oxygen and nutrients to the infant, and the arterial carrying waste products from the fetus. Here, we sampled arterial and venous umbilical cords separately from 48 newly delivered infants and examined plasma metabolomes using GC-MS/MS metabolomics. We investigated differences in metabolomes between arterial and venous blood and their associations with gestational length, birth weight, sex, and whether the baby was the first born or not, as well as maternal age and BMI. Using multilevel random forest analysis, a classification rate of 79% was achieved for arteriovenous differences (p = 0.004). Several monosaccharides had higher concentrations in the arterial cord plasma while amino acids were higher in venous plasma, suggesting that the main differences in the measured arterial and venous plasma metabolomes are related to amino acid and energy metabolism. Venous cord plasma metabolites related to energy metabolism were positively associated with parity (77% classification rate, p = 0.004) while arterial cord plasma metabolites were not. This underlines the importance of defining cord blood type for metabolomic studies.
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| 4. |
- Iribarren, Cristina, 1993, et al.
(författare)
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Fecal luminal factors from patients with irritable bowel syndrome induce distinct gene expression of colonoids
- 2022
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Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 34:10
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Tidskriftsartikel (refereegranskat)abstract
- Background: Alteration of the host-microbiota cross talk at the intestinal barrier may participate in the pathophysiology of irritable bowel syndrome (IBS). Therefore, we aimed to determine effects of fecal luminal factors from IBS patients on the colonic epithelium using colonoids. Methods: Colon-derived organoid monolayers, colonoids, generated from a healthy subject, underwent stimulation with fecal supernatants from healthy subjects and IBS patients with predominant diarrhea, phosphate-buffered saline (PBS), or lipopolysaccharide (LPS). Cytokines in cell cultures and fecal LPS were measured by ELISA and mRNA gene expression of monolayers was analyzed using Qiagen RT2 Profiler PCR Arrays. The fecal microbiota profile was determined by the GA-map (TM) dysbiosis test and the fecal metabolite profile was analyzed by untargeted liquid chromatography/mass spectrometry. Key results: Colonoid monolayers stimulated with fecal supernatants from healthy subjects (n = 7), PBS (n = 4) or LPS (n = 3) presented distinct gene expression profiles, with some overlap ((RY)-Y-2 = 0.70, Q(2) = 0.43). Addition of fecal supernatants from healthy subjects and IBS patients (n = 9) gave rise to different gene expression profiles of the colonoid monolayers ((RY)-Y-2 = 0.79, Q(2) = 0.64). Genes (n = 22) related to immune response (CD1D, TLR5) and barrier integrity (CLDN15, DSC2) contributed to the separation. Levels of proinflammatory cytokines in colonoid monolayer cultures were comparable when stimulated with fecal supernatants from either donor types. Fecal microbiota and metabolite profiles, but not LPS content, differed between the study groups. Conclusions: Fecal luminal factors from IBS patients induce a distinct colonic epithelial gene expression, potentially reflecting the disease pathophysiology. The culture of colonoids from healthy subjects with fecal supernatants from IBS patients may facilitate the exploration of IBS related intestinal micro-environmental and barrier interactions.
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| 5. |
- Koistinen, Ville M., et al.
(författare)
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Metabolite pattern derived from Lactiplantibacillus plantarum : fermented rye foods and in vitro gut fermentation synergistically inhibits bacterial growth
- 2022
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Ingår i: Molecular Nutrition & Food Research. - : John Wiley & Sons. - 1613-4125 .- 1613-4133. ; 66:21
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Tidskriftsartikel (refereegranskat)abstract
- Scope: Fermentation improves many food characteristics using microbes, such as lactic acid bacteria (LAB). Recent studies suggest fermentation may also enhance the health properties, but mechanistic evidence is lacking. We aimed to identify a metabolite pattern reproducibly produced during sourdough and in vitro colonic fermentation of various whole-grain rye products and how it affects the growth of bacterial species of potential importance to health and disease.Methods and results: We used Lactiplantibacillus plantarum DSMZ 13890 strain, previously shown to favour rye as its substrate. Using LC-MS metabolomics, we found seven microbial metabolites commonly produced during the fermentations, including dihydroferulic acid, dihydrocaffeic acid, and five amino acid metabolites, and stronger inhibition was achieved when exposing the bacteria to a mixture of the metabolites in vitro compared to individual compound exposures.Conclusion: Our study suggests that metabolites produced by LAB may synergistically modulate the local microbial ecology, such as in the gut. This could provide new hypotheses on how fermented foods influence human health via diet–microbiota interactions.
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| 6. |
- Moraes Holst, Luiza, et al.
(författare)
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Fecal Luminal Factors from Patients with Gastrointestinal Diseases Alter Gene Expression Profiles in Caco-2 Cells and Colonoids
- 2022
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1422-0067 .- 1661-6596. ; 23:24
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Tidskriftsartikel (refereegranskat)abstract
- Previous in vitro studies have shown that the intestinal luminal content, including metabolites, possibly regulates epithelial layer responses to harmful stimuli and promotes disease. Therefore, we aimed to test the hypothesis that fecal supernatants from patients with colon cancer (CC), ulcerative colitis (UC) and irritable bowel syndrome (IBS) contain distinct metabolite profiles and establish their effects on Caco-2 cells and human-derived colon organoids (colonoids). The metabolite profiles of fecal supernatants were analyzed by liquid chromatography-mass spectrometry and distinguished patients with CC (n = 6), UC (n = 6), IBS (n = 6) and healthy subjects (n = 6). Caco-2 monolayers and human apical-out colonoids underwent stimulation with fecal supernatants from different patient groups and healthy subjects. Their addition did not impair monolayer integrity, as measured by transepithelial electrical resistance; however, fecal supernatants from different patient groups and healthy subjects altered the gene expression of Caco-2 monolayers, as well as colonoid cultures. In conclusion, the stimulation of Caco-2 cells and colonoids with fecal supernatants derived from CC, UC and IBS patients altered gene expression profiles, potentially reflecting the luminal microenvironment of the fecal sample donor. This experimental approach allows for investigating the crosstalk at the gut barrier and the effects of the gut microenvironment in the pathogenesis of intestinal diseases.
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| 7. |
- Ronkainen, Justiina, et al.
(författare)
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LongITools: Dynamic longitudinal exposome trajectories in cardiovascular and metabolic noncommunicable diseases
- 2022
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Ingår i: Environmental Epidemiology. - 2474-7882. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- The current epidemics of cardiovascular and metabolic noncommunicable diseases have emerged alongside dramatic modifications in lifestyle and living environments. These correspond to changes in our "modern" postwar societies globally characterized by rural-to-urban migration, modernization of agricultural practices, and transportation, climate change, and aging. Evidence suggests that these changes are related to each other, although the social and biological mechanisms as well as their interactions have yet to be uncovered. LongITools, as one of the 9 projects included in the European Human Exposome Network, will tackle this environmental health equation linking multidimensional environmental exposures to the occurrence of cardiovascular and metabolic noncommunicable diseases.
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