| 1. |
- Bagavathy Shanmugam, Karthikeyan, et al.
(författare)
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Prenatal exposure to environmental contaminants and cord serum metabolite profiles in future immune-mediated diseases
- 2024
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Ingår i: Journal of Exposure Science and Environmental Epidemiology. - : Nature Publishing Group. - 1559-0631 .- 1559-064X.
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Prenatal exposure to environmental contaminants is a significant health concern because it has the potential to interfere with host metabolism, leading to adverse health effects in early childhood and later in life. Growing evidence suggests that genetic and environmental factors, as well as their interactions, play a significant role in the development of autoimmune diseases.OBJECTIVE: In this study, we hypothesized that prenatal exposure to environmental contaminants impacts cord serum metabolome and contributes to the development of autoimmune diseases.METHODS: We selected cord serum samples from All Babies in Southeast Sweden (ABIS) general population cohort, from infants who later developed one or more autoimmune-mediated and inflammatory diseases: celiac disease (CD), Crohn's disease (IBD), hypothyroidism (HT), juvenile idiopathic arthritis (JIA), and type 1 diabetes (T1D) (all cases, N = 62), along with matched controls (N = 268). Using integrated exposomics and metabolomics mass spectrometry (MS) based platforms, we determined the levels of environmental contaminants and metabolites.RESULTS: Differences in exposure levels were found between the controls and those who later developed various diseases. High contaminant exposure levels were associated with changes in metabolome, including amino acids and free fatty acids. Specifically, we identified marked associations between metabolite profiles and exposure levels of deoxynivalenol (DON), bisphenol S (BPS), and specific per- and polyfluorinated substances (PFAS).IMPACT STATEMENT: Abnormal metabolism is a common feature preceding several autoimmune and inflammatory diseases. However, few studies compared common and specific metabolic patterns preceding these diseases. Here we hypothesized that exposure to environmental contaminants impacts cord serum metabolome, which may contribute to the development of autoimmune diseases. We found differences in exposure levels between the controls and those who later developed various diseases, and importantly, on the metabolic changes associated with the exposures. High contaminant exposure levels were associated with specific changes in metabolome. Our study suggests that prenatal exposure to specific environmental contaminants alters the cord serum metabolomes, which, in turn, might increase the risk of various immune-mediated diseases.
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| 2. |
- Ghaffarzadegan, Tannaz, et al.
(författare)
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Determination of bile acids by hollow fibre liquid-phase microextraction coupled with gas chromatography.
- 2014
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Ingår i: Journal of Chromatography. B. - : Elsevier BV. - 1873-376X .- 1570-0232. ; 944, s. 69-74
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Tidskriftsartikel (refereegranskat)abstract
- A method based on hollow-fibre liquid phase microextraction combined with gas chromatography was developed for determination of specific bile acids in caecal materials of rats. Nine unconjugated bile acids, including the primary bile acids (cholic acid, chenodeoxycholic acid and α-muricholic acid) and the secondary bile acids (lithocholic acid, deoxycholic acid, ursodeoxycholic acid, hyodeoxycholic acid, β-muricholic acid and ω-muricholic acid) were quantified. Extraction conditions were evaluated, including: sample pH, type of organic solvent and amount of caecal material to be extracted. To compensate for sample matrix effects during extraction the method of standard addition was applied. The satisfactory linearity (r(2)>0.9840), high recovery (84.2-108.7%) and good intra-assay (6.3-10.6%) and inter-assay (6.9-11.1%) precision illustrated the good performance of the present method. The method is rapid, simple and capable of detecting and determining bile acids with limit of detection (LOD) ranged from 0.002 to 0.067μg/mL and limits of quantification (LOQ) varied from 0.006 to 0.224μg/mL. The results indicated that the concentration of some secondary bile acids, which usually are associated with health problems, were lower in rats fed with fermentable dietary fibre compared with a fibre free control diet, while the concentration of primary bile acids, usually connected with positive health effects, were higher in rats fed with diets containing dietary fibre. Of the dietary fibres, guar gum and to some extent the mixture of pectin+guar gum had the most positive effects. Thus, it was concluded that the composition of bile acids can be affected by the type of diet.
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| 3. |
- Ghaffarzadegan, Tannaz, et al.
(författare)
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Determination of free and conjugated bile acids in serum of Apoe(−/−) mice fed different lingonberry fractions by UHPLC-MS
- 2019
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Bile acids (BAs) are known to be involved in cholesterol metabolism but interactions between the diet, BA profiles, gut microbiota and lipid metabolism have not been extensively explored. In the present study, primary and secondary BAs including their glycine and taurine-conjugated forms were quantified in serum of Apoe−/− mice by protein precipitation followed by reversed phase ultra-high-performance liquid chromatography and QTOF mass spectrometry. The mice were fed different lingonberry fractions (whole, insoluble and soluble) in a high-fat setting or cellulose in a high and low-fat setting. Serum concentrations of BAs in mice fed cellulose were higher with the high-fat diet compared to the low-fat diet (20–70%). Among the lingonberry diets, the diet containing whole lingonberries had the highest concentration of chenodeoxycholic acid (CDCA), ursodeoxycholic acid (UDCA), tauro-ursodeoxycholic acid (T-UDCA), α and ω-muricholic acids (MCA) and tauro-α-MCA (T-α-MCA), and the lowest concentration of tauro-cholic acid (T-CA), deoxycholic acid (DCA) and tauro-deoxycholic acid (T-DCA). The glycine-conjugated BAs were very similar with all diets. CDCA, UDCA and α-MCA correlated positively with Bifidobacterium and Prevotella, and T-UDCA, T-α-MCA and ω-MCA with Bacteroides and Parabacteroides.
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| 4. |
- Ghaffarzadegan, Tannaz, et al.
(författare)
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Effects of barley variety, dietary fiber and β-glucan content on bile acid composition in cecum of rats fed low- and high-fat diets
- 2018
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Ingår i: Journal of Nutritional Biochemistry. - : Elsevier BV. - 0955-2863. ; 53, s. 104-110
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Tidskriftsartikel (refereegranskat)abstract
- Diet-induced obesity and insulin resistance have been linked to changes in bile acid (BA) profiles, which in turn are highly dependent on the dietary composition and activity of the gut microbiota. The objective of the present study was to investigate whether the type and level of fiber had an effect on cecal BA composition when included in low- and high-fat diets. Groups of rats were fed two barley varieties, which resulted in three test diets containing three levels of β-glucans and two levels of dietary fiber. BAs were preconcentrated using hollow fiber liquid-phase microextraction and quantified by gas chromatography. The amount of the secondary BAs, lithocholic-, deoxycholic- and hyodexycholic acids was generally higher in groups fed high-fat diets compared with corresponding acids in groups fed low-fat diets (P<.05). In contrast, most of the primary and the secondary BAs, ursodeoxycholic acid and β- and ω-muricholic acids, were two to five times higher (P<.05) in groups fed low-fat diets than in groups fed high-fat diets. This was particularly true for groups fed the highest level of β-glucans and in some cases also the medium level. The BA profile in the gut was strongly dependent on the amount and type of dietary fiber in the diet, which may be useful in the prevention/treatment of diseases associated with changes in BA profiles.
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| 5. |
- Ghaffarzadegan, Tannaz, et al.
(författare)
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Molecular properties of guar gum and pectin modify cecal bile acids, microbiota, and plasma lipopolysaccharide-binding protein in rats
- 2016
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:6
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Tidskriftsartikel (refereegranskat)abstract
- Bile acids (BAs) act as signaling molecules in various physiological processes, and are related to colonic microbiota composition as well as to different types of dietary fat and fiber. This study investigated whether guar gum and pectin-two fibers with distinct functional characteristics-affect BA profiles, microbiota composition, and gut metabolites in rats. Low- (LM) or high-methoxylated (HM) pectin, and low-, medium-, or high-molecular-weight (MW) guar gum were administered to rats that were fed either low- or high-fat diets. Cecal BAs, short-chain fatty acids (SCFA) and microbiota composition, and plasma lipopolysaccharide-binding protein (LBP) levels were analyzed, by using novel methodologies based on gas chromatography (BAs and SCFAs) and 16S rRNA gene sequencing on the Illumina MiSeq platform. Strong correlations were observed between cecal BA and SCFA levels, microbiota composition, and portal plasma LBP levels in rats on a high-fat diet. Notably, guar gum consumption with medium-MW increased the cecal amounts of cholic-, chenodeoxycholic-, and ursodeoxycholic acids as well as α-, β-, and ù-muricholic acids to a greater extent than other types of guar gum or the fiber-free control diet. In contrast, the amounts of cecal deoxycholic- and hyodeoxycholic acid were reduced with all types of guar gum independent of chain length. Differences in BA composition between pectin groups were less obvious, but cecal levels of α- and ù-muricholic acids were higher in rats fed LM as compared to HM pectin or the control diet. The inflammatory marker LBP was downregulated in rats fed medium-MW guar gum and HM pectin; these two fibers decreased the cecal abundance of Oscillospira and an unclassified genus in Ruminococcaceae, and increased that of an unclassified family in RF32. These results indicate that the molecular properties of guar gum and pectin are important for their ability to modulate cecal BA formation, gut microbiota composition, and high-fat diet induced inflammation.
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| 6. |
- Ghaffarzadegan, Tannaz, et al.
(författare)
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Postprandial Responses of Serum Bile Acids in Healthy Humans After Ingestion of Turmeric Before Medium /High‐Fat Breakfasts
- 2019
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Ingår i: Molecular Nutrition and Food Research. - : Wiley. - 1613-4133 .- 1613-4125.
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Tidskriftsartikel (refereegranskat)abstract
- Scope: Bile acids (BAs) are known to regulate a number of metabolic activities in the body. However, very little is known about how BAs are affected by diet. This study aimed to investigate whether a single-dose of turmeric-based beverage (TUR) before ingestion of medium- (MF) or high-fat (HF) breakfasts would improve the BA profile in healthy subjects. Methods and results: Twelve healthy subjects were assigned to a randomized crossover single-blind study. The subjects received iso-caloric MF or HF breakfasts after a drink containing flavored water with or without an extract of turmeric with at least one-week wash-out period between the treatments. Postprandial BAs were measured using protein precipitation followed by ultra-high-performance liquid chromatography-mass spectrometry analysis (UHPLC-MS). The concentration of BAs was generally higher after HF than MF breakfasts. Ingestion of TUR before MF breakfast increased the serum concentrations of free and conjugated forms of cholic and ursodeoxycholic acids, as well as the concentrations of chenodeoxycholic acid and its taurine-conjugated form. However, the concentration of conjugated forms of deoxycholic acid decreased when TUR was taken before HF breakfast. Conclusion: TUR ingestion before MF and HF breakfasts improved BA profiles and may therefore have potential health-promoting effects on BA metabolism.
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| 7. |
- Ghaffarzadegan, Tannaz
(författare)
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Regulation of bile acids by prebiotic food components : Studies in rat caecum and in serum of mice and humans
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Bile acids (BA) are formed from cholesterol in the liver and, apart from being part of fat digestion, they also act as signalling molecules in several health-related physiological processes. BA composition is regulated by gut microbiota as well as dietary fibre (DF) and fat in the diet. This thesis describes how different types of DF and fat levels, can alter BA composition in the caecum/faeces and blood. One methodology for analysing BAs in caecum was developed, while another methodology was set up to analyse BAs in blood/serum samples. In the first study, the method developed for BA analysis in caecum materials was based on hollow-fibre liquid-phase microextraction followed by gas chromatography with flame ionization detector. The method was applied by analysing the caecum content of rats fed three diets containing fermentable DF: pectin, guar gum and a mixture of the two, and a fibre-free control diet. All diets containing DF increased the total amounts of BAs related to beneficial health effects and reduced the amounts of those connected to diseases and cancers. Furthermore, an in vivo study of rats given guar gum of three different viscosities and pectin with two different degrees of methoxylation in low-fat (LF) and high-fat (HF) settings was performed. Guar gum with medium viscosity showed the best BA profile, containing higher amounts of BAs connected to health, and lower amounts of BAs associated with disease. There was a strong correlation between the gut microbiota, BAs and caecal short-chain fatty acids (SCFAs). BAs with beneficial health properties and SCFAs, with the exception of valeric acid, correlated positively with Bifidobacterium and RF32 and they were higher in groups fed fibre. The amounts of BAs connected to diseases were positively correlated with Firmicutes and were higher in groups fed the fibre-free control diet. The pectins behaved similarly and their effects on BA compositions were less pronounced. In study III, two barley varieties with different levels of DF and β-glucan in LF and HF settings were evaluated. In the LF groups, the higher content of β-glucan showed higher amounts of the health-promoting BAs, while in the HF setting the group with medium β-glucan content and highest amounts of arabinoxylan showed an increase in these BAs. The arabinoxylan seemed to be more effective at reducing the levels of BAs connected with negative effects (than the β-glucan), both in LF and HF settings. The BAs with beneficial health effects were associated with Bifidobacterium and Lactobacillus and their abundance was higher in LF diets. In study IV, free and conjugated BAs in serum samples from hearts of mice were determined using simple protein precipitation followed by ultra-high-performance liquid chromatography–mass spectrometry. Different lingonberry samples, consisting of soluble, insoluble or whole lingonberry fractions in a HF diet or cellulose in LF and HF diets, were investigated. The whole lingonberries showed a healthier BA profile and a greater abundance of Bifidobacterium and Prevotella. In study V, postprandial serum concentrations of BAs in healthy subjects after consumption of a turmeric-based beverage prior to medium-fat and HF breakfasts were registered. Turmeric could modify the BA profile towards a healthier composition, with higher levels of free and conjugated forms of cholic and ursodeoxycholic acids as well as free and taurine-conjugated forms of chenodeoxycholic acid but lower levels of conjugated forms of deoxycholic acid. In conclusion, using the new set of methodologies, the BA composition in rat caecum and in mice and human serum could be studied after the intake of different diets. The type and functional properties of prebiotic chosen, and the amount of fat can affect the BA profile and gut microbiota composition. A HF diet increased the total amounts of BAs in blood and caecum, as usually assumed. Less well-known is that fermentable DF can also shape the BA profile. The results of this work may be the basis for development of prebiotic food products for the promotion of improved BA metabolism and overall health.
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| 8. |
- Hyötyläinen, Tuulia, 1971-, et al.
(författare)
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Cord serum metabolic signatures of future progression to immune-mediated diseases
- 2023
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Ingår i: iScience. - : Cell Press. - 2589-0042. ; 26:3
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Tidskriftsartikel (refereegranskat)abstract
- Previous prospective studies suggest that progression to autoimmune diseases is preceded by metabolic dysregulation, but it is not clear which metabolic changes are disease-specific and which are common across multiple immune-mediated diseases. Here we investigated metabolic profiles in cord serum in a general population cohort (All Babies In Southeast Sweden; ABIS), comprising infants who progressed to one or more immune-mediated diseases later in life: type 1 diabetes (n = 12), celiac disease (n = 28), juvenile idiopathic arthritis (n = 9), inflammatory bowel disease (n = 7), and hypothyroidism (n = 6); and matched controls (n = 270). We observed elevated levels of multiple triacylglycerols (TGs) an alteration in several gut microbiota related metabolites in the autoimmune groups. The most distinct differences were observed in those infants who later developed HT. The specific similarities observed in metabolic profiles across autoimmune diseases suggest that they share specific common metabolic phenotypes at birth that contrast with those of healthy controls.
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| 9. |
- Hyötyläinen, Tuulia, 1971-, et al.
(författare)
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Impact of Environmental Exposures on Human Breast Milk Lipidome in Future Immune-Mediated Diseases
- 2024
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Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 58:5, s. 2214-2223
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Tidskriftsartikel (refereegranskat)abstract
- The composition of human breast milk (HBM) exhibits significant variability both between individuals and within the same individual. While environmental factors are believed to play a role in this variation, their influence on breast milk composition remains inadequately understood. Herein, we investigate the impact of environmental factors on HBM lipid composition in a general population cohort. The study included mothers (All Babies In Southeast Sweden study) whose children later progressed to one or more immune-mediated diseases later in life: type 1 diabetes (n = 9), celiac disease (n = 24), juvenile idiopathic arthritis (n = 9), inflammatory bowel disease (n = 7), hypothyroidism (n = 6), and matched controls (n = 173). Lipidome of HBM was characterized by liquid chromatography combined with high-resolution mass spectrometry. We observed that maternal age, body mass index, diet, and exposure to perfluorinated alkyl substances (PFASs) had a marked impact on breast milk lipidome, with larger changes observed in the milk of those mothers whose children later developed autoimmune diseases. We also observed differences in breast milk lipid composition in those mothers whose offspring later developed autoimmune diseases. Our study suggests that breast milk lipid composition is modified by a complex interaction between genetic and environmental factors, and, importantly, this impact was significantly more pronounced in those mothers whose offspring later developed autoimmune/inflammatory diseases. Our findings also suggest that merely assessing PFAS concentration may not capture the full extent of the impact of chemical exposures; thus, the more comprehensive exposome approach is essential for accurately assessing the impact of PFAS exposure on HBM and, consequently, on the health outcomes of the offspring.
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| 10. |
- Nguyen, Thao Duy, et al.
(författare)
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Monobutyrin and monovalerin improve gut-blood-brain biomarkers and alter gut microbiota composition in high-fat fed apolipoprotein-E-knockout rats
- 2022
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Monobutyrin (MB) and monovalerin (MV), glycerol esters of short-chain fatty acids (SCFAs), have been shown to positively influence lipid profile and biomarkers in the gut and brain. This study examined whether MB and MV in high-fat diets, affected microbiota composition and gut-blood-brain markers in apolipoprotein E deficient (ApoE-/-) rats, a model for studies of lipid-associated disorders, and neurodegenerative processes in Alzheimer's disease (AD). ApoE-/- rats fed MB and MV increased Tenericutes and the brain neurotransmitter γ-aminobutyric acid (GABA), while the blood stress hormone corticosterone decreased compared to control rats. Only rats that received MB showed a significant increase in cholic acid and Adlercreutzia in the caecum. In rats fed MV, the decrease of Proteobacteria was associated with decreased corticosterone levels. Conclusively, dietary supplementation of SCFA glycerol esters can modulate gut-blood-brain markers and alter gut microbiota composition in ApoE-/- rats, suggesting that SCFAs also could counteract lipid disorders-related diseases.
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