Browse
Submit Data
Databases
API
Help

Dataset Information

17 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Cholestasis alters brain lipid and bile acid composition and compromises motor function in neonatal piglets.

ABSTRACT: Infants with neonatal cholestasis are prone to neurodevelopmental deficits, however, the underlying pathogenesis is unclear. Lipid malabsorption and accumulation of potentially neurotoxic molecules in the blood such as bile acids are important yet relatively unexplored pathways. Here, we developed a translational piglet model to understand how the molecular bile acid and lipid composition of the brain is affected by this disease and relates to motor function. Piglets (8-days old) had bile duct ligation or sham surgery and were fed a formula diet for 3 weeks. Alongside sensory-motor deficits observed in bile duct-ligated animals, we found a shift toward a more hydrophilic and conjugated bile acid profile in the brain. Additionally, comprehensive lipidomics of the cerebellum revealed a decrease in total lipids including phosphatidylinositols and phosphatidylserines and increases in lysophospholipid species. This was paralleled by elevated cerebellar expression of genes related to inflammation and tissue damage albeit without significant impact on the brain transcriptome. This study offers new insights into the developing brain's molecular response to neonatal cholestasis indicating that bile acids and lipids may contribute in mediating motor deficits.

SUBMITTER: Henriksen NL

PROVIDER: S-EPMC9277266 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Obstructive cholestasis compromises balance and alters brain lipid composition in neonatal piglets

Project description:Infants with neonatal cholestasis are prone to neurodevelopmental deficits including neuromotor function. Accumulation of potentially neurotoxic molecules in the bloodstream including ammonia and bile acids and malabsorption of lipids may affect neurodevelopment in these patients. This study examined neuromotor function and bile acid and lipid composition of the brain in a piglet model of obstructive neonatal cholestasis via bile duct ligation (BDL) surgery. Results showed that BDL piglets had compromised balance and increased liver enzyme levels, liver fibrosis and bile duct proliferation compared to SHAM piglets. Plasma and cerebellum bile acid profiles differed between BDL and SHAM piglets with hyocholic acid and conjugated bile acid forms dominating in the BDL group. In the cerebellum there were different lipid profiles, but similar gene expression profiles between the two groups.

2022-06-01 | GSE180600 | GEO

Obstructive cholestasis compromises balance and alters brain lipid composition in neonatal piglets

Project description:Obstructive cholestasis compromises balance and alters brain lipid composition in neonatal piglets

| PRJNA748765 | ENA

Gut Microbiota Dysbiosis Associated with Bile Acid Metabolism in Neonatal Cholestasis Disease.

Project description:Neonatal cholestasis disease (NCD) is a complex and easily mis-diagnosed condition. We analyzed microbiota community structure in feces and measured short-chain fatty acids, bile acids (BAs) and liver function of 12 healthy, 13 NCD, and 13 treated infants after diagnosis. Based on 16S rRNA gene amplicon sequencing and gas-chromatographic-mass-spectrometric analysis of secondary BAs, we identified microbial genera and metabolites that associate with abnormal bile secretion. Streptococcus gallolyticus and Parabacteroides distasonis, and Lactobacillus gasseri had higher relative abundance in healthy and NCD infants respectively. Compared to NCD patients, healthy infants had higher LCA, CDCA and GCDCA fecal concentrations. The three microbial species and three secondary bile acids were selected as potential non-invasive combined biomarkers to diagnose NCD. We propose that microbiota-metabolite combined biomarkers could be used for diagnosis of NCD, and this may contribute to improved early clinical diagnosis of NCD in the future.

| S-EPMC7203226 | biostudies-literature

Gut microbiota alters host bile acid metabolism to contribute to intrahepatic cholestasis of pregnancy.

Project description:Intrahepatic cholestasis of pregnancy (ICP) is a female pregnancy-specific disorder that is characterized by increased serum bile acid and adverse fetal outcomes. The aetiology and mechanism of ICP are poorly understood; thus, existing therapies have been largely empiric. Here we show that the gut microbiome differed significantly between individuals with ICP and healthy pregnant women, and that colonization with gut microbiome from ICP patients was sufficient to induce cholestasis in mice. The gut microbiomes of ICP patients were primarily characterized by Bacteroides fragilis (B. fragilis), and B. fragilis was able to promote ICP by inhibiting FXR signaling via its BSH activity to modulate bile acid metabolism. B. fragilis-mediated FXR signaling inhibition was responsible for excessive bile acid synthesis and interrupted hepatic bile excretion to ultimately promote the initiation of ICP. We propose that modulation of the gut microbiota-bile acid-FXR axis may be of value for ICP treatment.

| S-EPMC9998625 | biostudies-literature

Biliary lipid composition in idiopathic bile acid malabsorption.

Project description:BACKGROUND: Chronic diarrhoea is the clinical hallmark of patients presenting with idiopathic bile acid malabsorption. Its pathogenesis is unknown; colonic water secretion can be induced by dihydroxy bile acids, but it is not known whether enrichment of the bile acid pool with these bile acids occurs in such patients. Furthermore, bile acid malabsorption is known to affect biliary lipid composition, but no information is available for the idiopathic type. AIMS: To verify: (a) whether diarrhoea in patients with idiopathic bile acid malabsorption is associated with enrichment of the bile acid pool with dihydroxy bile acids; and (b) whether supersaturation with cholesterol of duodenal bile occurs in such patients as a result of chronic bile acid depletion. PATIENTS: Thirteen patients with idiopathic bile acid malabsorption diagnosed according to abnormal 75SeHCAT test and absence of other organic diseases, and 23 control subjects. METHODS: Bile rich duodenal fluid was collected during intravenous ceruletide infusion in the fasting state. Biliary lipids were analysed by enzymatic assays and bile acids by high performance liquid chromatography. RESULTS: Patients with idiopathic bile acid malabsorption had a cholesterol saturation index similar to controls. Bile acid composition showed only a decrease in percentage cholic acid (29 (2)% versus 36 (2)%; p<0.05); the dihydroxy:trihydroxy bile acid ratio was similar to controls. CONCLUSIONS: Patients with idiopathic bile acid malabsorption do not have an increased risk of forming cholesterol gallstones. The mechanism of diarrhoea does not seem to depend on an enrichment of the bile acid pool with dihydroxy bile acids.

| S-EPMC1727337 | biostudies-other

Porcine deltacoronavirus infection alters bacterial communities in the colon and feces of neonatal piglets.

Project description:Porcine deltacoronavirus (PDCoV) is a novel enteropathogenic coronavirus that causes watery diarrhea in piglets. Little is known regarding the alteration of the gut microbiota in PDCoV-induced diarrhea piglets. In this study, 5-day-old piglets were experimentally infected with PDCoV strain CH-01, and all piglets developed typical clinical disease, characterized by acute and severe watery diarrhea. Histologic lesions were limited to the villous epithelium of the duodenum and ileum. Gut microbiota profiles in the colon and feces of piglets inoculated with PDCoV were investigated using 16S rRNA sequencing. The results showed that PDCoV infection reduced bacterial diversity and significantly altered the composition of the microbiota from the phylum to the genus level in the colon and feces of piglets. Firmicutes (phylum), Lactobacillaceae (family), and Lactobacillus (genus) were significantly increased (p < .01), while the abundance of Bacteroidetes (phylum) was markedly reduced in the colon and feces of the PDCoV-infected piglets (p < .01) when compared to those of the healthy piglets. Furthermore, microbial function prediction indicated that the changes in the intestinal flora also affected the nucleotide transport and metabolism, defense, translation, and transcription function of the intestinal microbiota. The current study provides new insight into the pathology and physiology of PDCoV.

| S-EPMC7349149 | biostudies-literature

Serum Apolipoprotein H Alters Cellular Lipid Composition to Inhibit Ferroptosis

Project description:Ferroptosis is an iron-dependent regulated cell death caused by the accumulation of lipid peroxidation for the uncontrolled metabolism. Serum, as the major medium for the cultured cells, resembles the contents of the extracellular fluid in vivo and provides biomolecules for cellular metabolism. The efficiency of ferroptosis induction is influenced by several factors including the extracellular environment. However, the effect of serum on ferroptosis remains largely unclear. We found that cells cultured in different serums have varying efficiencies in ferroptosis induction. By purifying and identifying active serum components, we discovered that serum protein apolipoprotein H (APOH) play essential role in inhibiting ferroptosis. Moreover, APOH activates the phosphoinositide 3-kinase (PI3K)/AKT-Sterol regulatory element-binding proteins (SREBPs) pathway. SREBPs upregulate the stearoyl-CoA desaturase (SCD) increasing cellular monounsaturated fatty acid-containing phospholipids (MUFA-PLs), leading to ferroptosis inhibition. Our findings indicate that APOH, as an extracellular protein, plays an important role in cellular lipid metabolism and inhibition of ferroptosis, thus may having therapeutic applications in cancer treatment and ferroptosis-related diseases.

2024-10-09 | GSE237178 | GEO

New generation lipid emulsions increase brain DHA and improve body composition, but not short-term neurodevelopment in parenterally-fed preterm piglets.

Project description:New generation, multicomponent parenteral lipid emulsions provide key fatty acids for brain growth and development, such as docosahexaenoic acid (DHA) and arachidonic acid (AA), yet the content may be suboptimal for preterm infants. Our aim was to test whether DHA and AA-enriched lipid emulsions would increase activity, growth, and neurodevelopment in preterm piglets and limit brain inflammation. Cesarean-delivered preterm pigs were given three weeks of either enteral preterm infant formula (ENT) or TPN with one of three parenteral lipid emulsions: Intralipid (IL), SMOFlipid (SMOF) or an experimental emulsion (EXP). Activity was continuously monitored and weekly blood sampling and behavioral field testing performed. At termination of the study, whole body and tissue metrics were collected. Neuronal density was assessed in sections of hippocampus (HC), thalamus, and cortex. Frontal cortex (FC) and HC tissue were assayed for fatty acid profiles and expression of genes of neuronal growth and inflammation. After 3?weeks of treatment, brain DHA content in SMOF, EXP and ENT pigs was higher (P?<?0.01) in FC but not HC vs. IL pigs. There were no differences in brain weight or neuron density among treatment groups. Inflammatory cytokine TNF? and IL-1? expression in brain regions were increased in IL pigs (P?<?0.05) compared to other groups. Overall growth velocity was similar among groups, but IL pigs had higher percent body fat and increased insulin resistance compared to other treatments (P?<?0.05). ENT pigs spent more time in higher physical activity levels compared to all TPN groups, but there were no differences in exploratory behavior among groups. We conclude that a soybean oil emulsion increased select brain inflammatory cytokines and multicomponent lipid emulsions enriched with DHA and AA in parenteral lipids results in increased cortical DHA and improved body composition without affecting short term neurodevelopmental outcomes.

| S-EPMC6813879 | biostudies-literature

Cholestasis-induced adaptive remodeling of interlobular bile ducts.

Project description:UnlabelledCholestasis is a common complication in liver diseases that triggers a proliferative response of the biliary tree. Bile duct ligation (BDL) is a frequently used model of cholestasis in rodents. To determine which changes occur in the three-dimensional (3D) architecture of the interlobular bile duct during cholestasis, we used 3D confocal imaging, surface reconstructions, and automated image quantification covering a period up to 28 days after BDL. We show a highly reproducible sequence of interlobular duct remodeling, where cholangiocyte proliferation initially causes corrugation of the luminal duct surface, leading to an approximately five-fold increase in surface area. This is analogous to the function of villi in the intestine or sulci in the brain, where an expansion of area is achieved within a restricted volume. The increase in surface area is further enhanced by duct branching, branch elongation, and loop formation through self-joining, whereby an initially relatively sparse mesh surrounding the portal vein becomes five-fold denser through elongation, corrugation, and ramification. The number of connections between the bile duct and the lobular bile canalicular network by the canals of Hering decreases proportionally to the increase in bile duct length, suggesting that no novel connections are established. The diameter of the interlobular bile duct remains constant after BDL, a response that is qualitatively distinct from that of large bile ducts, which tend to enlarge their diameters. Therefore, volume enhancement is only due to net elongation of the ducts. Because curvature and tortuosity of the bile duct are unaltered, this enlargement of the biliary tree is caused by branching and not by convolution.ConclusionBDL causes adaptive remodeling that aims at optimizing the intraluminal surface area by way of corrugation and branching.

| S-EPMC5066759 | biostudies-literature

Heat Stress in Dairy Cattle Alters Lipid Composition of Milk.

Project description:Heat stress, potentially affecting both the health of animals and the yield and composition of milk, occurs frequently in tropical, sub-tropical and temperate regions. A simulated acute heat stress experiment was conducted in controlled-climate chambers and milk samples collected before, during and after the heat challenge. Milk lipid composition, surveyed using LC-MS, showed significant changes in triacylglycerol (TAG) and polar lipid profiles. Heat stress (temperature-humidity index up to 84) was associated with a reduction in TAG groups containing short- and medium-chain fatty acids and a concomitant increase in those containing long-chain fatty acids. The abundance of five polar lipid classes including phosphatidylethanolamine, phosphatidylserine, phosphatidylcholine, lysophosphatidylcholine and glucosylceramide, was found to be significantly reduced during heat stress. Lysophosphatidylcholine, showing the greatest reduction in concentration, also displayed a differential response between heat tolerant and heat susceptible cows during heat stress. This phospholipid could be used as a heat stress biomarker for dairy cattle. Changes in TAG profile caused by heat stress are expected to modify the physical properties of milk fat, whereas the reduction of phospholipids may affect the nutritional value of milk. The results are discussed in relation to animal metabolism adaptation in the event of acute heat stress.

| S-EPMC5430412 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data