Postnatal prebiotic supplementation in rats affects adult anxious behaviour, hippocampus, electrophysiology, metabolomics, and gut microbiota.
Ontology highlight
ABSTRACT:
SUBMITTER: Spitzer SO
PROVIDER: S-EPMC8476651 | biostudies-literature | 2021 Oct
REPOSITORIES: biostudies-literature
Publications
Postnatal prebiotic supplementation in rats affects adult anxious behaviour, hippocampus, electrophysiology, metabolomics, and gut microbiota.
Spitzer Sonia O SO Tkacz Andrzej A Savignac Helene M HM Cooper Matthew M Giallourou Natasa N Mann Edward O EO Bannerman David M DM Swann Jonathan R JR Anthony Daniel C DC Poole Philip S PS Burnet Philip W J PWJ
iScience 20210910 10
We have shown previously that prebiotic (Bimuno galacto-oligosacharides, B-GOS®) administration to neonatal rats increased hippocampal NMDAR proteins. The present study has investigated the effects of postnatal B-GOS® supplementation on hippocampus-dependent behavior in young, adolescent, and adult rats and applied electrophysiological, metabolomic and metagenomic analyses to explore potential underlying mechanisms. The administration of B-GOS® to suckling, but not post-weaned, rats reduced anxi ...[more]
Similar Datasets
Project description:BackgroundAn inadequate perinatal nutritional environment can alter the maturation of the intestinal barrier and promote long-term pathologies such as metabolic syndrome or chronic intestinal diseases. The intestinal microbiota seems to play a determining role in the development of the intestinal barrier. In the present study, we investigated the impact of consuming an early postnatal prebiotic fiber (PF) on growth, intestinal morphology and the microbiota at weaning in postnatal-growth-restricted mice (PNGR).MethodsLarge litters (15 pups/mother) were generated from FVB/NRj mice to induce PNGR at postnatal day 4 (PN4) and compared to control litters (CTRL, 8 pups/mother). PF (a resistant dextrin) or water was orally administered once daily to the pups from PN8 to PN20 (3.5 g/kg/day). Intestinal morphology was evaluated at weaning (PN21) using the ileum and colon. Microbial colonization and short-chain fatty acid (SCFA) production were investigated using fecal and cecal contents.ResultsAt weaning, the PNGR mice showed decreased body weight and ileal crypt depth compared to the CTRL. The PNGR microbiota was associated with decreased proportions of the Lachnospiraceae and Oscillospiraceae families and the presence of the Akkermansia family and Enterococcus genus compared to the CTRL pups. The propionate concentrations were also increased with PNGR. While PF supplementation did not impact intestinal morphology in the PNGR pups, the proportions of the Bacteroides and Parabacteroides genera were enriched, but the proportion of the Proteobacteria phylum was reduced. In the CTRL pups, the Akkermansia genus (Verrucomicrobiota phylum) was present in the PF-supplemented CTRL pups compared to the water-supplemented ones.ConclusionsPNGR alters intestinal crypt maturation in the ileum at weaning and gut microbiota colonization. Our data support the notion that PF supplementation might improve gut microbiota establishment during the early postnatal period.
| S-EPMC10300902 | biostudies-literature
Project description:Humans can acquire fear through the observation of others' (learning models') threat responses. These responses can be direct responses to aversive stimuli, or anticipatory responses to threats. Most research focuses on learning from observation of direct responses only. Here, we investigated how observational fear conditioning is influenced by a learning model's typically anxious anticipatory responses. High anxiety individuals often display typically anxious anticipatory behaviour, such as worsened discrimination between safe and unsafe stimuli, characterized by increased threat responses to safe stimuli. We hypothesized that observation of an anxiously behaving model would worsen discriminatory learning. To this end, we developed an observational conditioning paradigm where a learning model was exposed to one safe and one unsafe stimuli. The learning model displayed anticipatory aversion to either to the unsafe stimulus only (Non-Anxious Model group) or to both the safe and unsafe stimuli (Anxious Model group) in addition to reacting directly to an aversive stimulus paired with the unsafe stimulus. Contrary to expectations, discriminatory learning was not worsened in the Anxious Model group compared to the Non-Anxious Model group. Rather, we saw more robust discriminatory learning in the Anxious Model group. The study provides a first step towards understanding the effect of other's anticipatory responses in general and typically anxious anticipatory responses in particular, on observational fear learning.
| S-EPMC6591253 | biostudies-literature
Project description:IntroductionObesity occurs partly due to consumption of a high-fat, high-sugar and low fiber diet and is associated with an altered gut microbiome. Prebiotic supplementation can reverse obesity and beneficially alter the gut microbiome, evidenced by previous studies in rodents. However, the role of the small intestinal metabolome in obese and prebiotic supplemented rodents has never been investigated.ObjectivesTo investigate and compare the small intestinal metabolome of healthy and obese rats, as well as obese rats supplemented with the prebiotic oligofructose (OFS).MethodsUntargeted metabolomics was performed on small intestinal contents of healthy chow-fed, high fat diet-induced obese, and obese rats supplemented with oligofructose using UPLC-MS/MS. Quantification of enterohepatic bile acids was performed with UPLC-MS to determine specific effects of obesity and fiber supplementation on the bile acid pool composition.ResultsThe small intestinal metabolome of obese rats was distinct from healthy rats. OFS supplementation did not significantly alter the small intestinal metabolome but did alter levels of several metabolites compared to obese rats, including bile acid metabolites, amino acid metabolites, and metabolites related to the gut microbiota. Further, obese rats had lower total bile acids and increased taurine-conjugated bile acid species in enterohepatic circulation; this effect was reversed with OFS supplementation in high fat-feeding.ConclusionObesity is associated with a distinct small intestinal metabolome, and OFS supplementation reverses some metabolite levels that were altered in obese rats. Future research into the effects of specific metabolites identified in this study will provide deeper insight into the mechanism of fiber supplementation on improved body weight.
| S-EPMC10234511 | biostudies-literature
Project description:BackgroundThere are complex interactions between aging, frailty, diet, and the gut microbiota; modulation of the gut microbiota by diet could lead to healthier aging. The purpose of this study was to test the effect of diets differing in sugar, fat, and fiber content upon the gut microbiota of mice humanized with microbiota from healthy or frail older people. We also performed a 6-month dietary fiber supplementation in three human cohorts representing three distinct life-stages.MethodsMice were colonized with human microbiota and then underwent an 8-week dietary intervention with either a high-fiber/low-fat diet typical of elderly community dwellers or a low-fiber/high-fat diet typical of long-stay residential care subjects. A cross-over design was used where the diets were switched after 4 weeks to the other diet type to identify responsive taxa and innate immunity changes. In the human intervention, the subjects supplemented their normal diet with a mix of five prebiotics (wheat dextrin, resistant starch, polydextrose, soluble corn fiber, and galactooligo-saccharide) at 10 g/day combined total, for healthy subjects and 20 g/day for frail subjects, or placebo (10 g/day maltodextrin) for 26 weeks. The gut microbiota was profiled and immune responses were assayed by T cell markers in mice, and serum cytokines in humans.ResultsHumanized mice maintained gut microbiota types reflecting the respective healthy or frail human donor. Changes in abundance of specific taxa occurred with the diet switch. In mice with the community type microbiota, the observed differences reflected compositions previously associated with higher frailty. The dominance of Prevotella present initially in community inoculated mice was replaced by Bacteroides, Alistipes, and Oscillibacter. Frail type microbiota showed a differential effect on innate immune markers in both conventional and germ-free mice, but a moderate number of taxonomic changes occurring upon diet switch with an increase in abundance of Parabacteroides, Blautia, Clostridium cluster IV, and Phascolarctobacterium. In the human intervention, prebiotic supplementation did not drive any global changes in alpha- or beta-diversity, but the abundance of certain bacterial taxa, particularly Ruminococcaceae (Clostridium cluster IV), Parabacteroides, Phascolarctobacterium, increased, and levels of the chemokine CXCL11 were significantly lower in the frail elderly group, but increased during the wash-out period.ConclusionsSwitching to a nutritionally poorer diet has a profound effect on the microbiota in mouse models, with changes in the gut microbiota from healthy donors reflecting previously observed differences between elderly frail and non-frail individuals. However, the frailty-associated gut microbiota did not reciprocally switch to a younger healthy-subject like state, and supplementation with prebiotics was associated with fewer detected effects in humans than diet adjustment in animal models.
| S-EPMC6417215 | biostudies-literature
Project description:BackgroundEarly postnatal overfeeding could result in metabolic imprinting that decreases energy expenditure following white adipose tissue (WAT) gain throughout life. This research investigated whether curcumin (CUR) supplementation could promote WAT browning and activate thermogenesis in postnatal overfed rats.Methods and resultsThis study adjusted the size of litters to three (small litters, SL) or ten (normal litters, NL) to mimic early postnatal overfeeding or normal feeding from postnatal day 3. From postnatal week 3 (weaning period), SL rats were fed a standard diet (SL) or a diet supplemented with 1% (SL1% CUR) or 2% (SL2% CUR) CUR for ten weeks. At postnatal week 13, SL rats with 1% or 2% CUR supplementation had lower body weight and less WAT gain and had an increased lean mass ratio, and their glucose tolerance and blood lipid levels had recovered to normal when compared to SL rats that did not receive the supplement. Moreover, the increased heat generation were consistent with the expression levels of uncoupling protein 1 (UCP1) and other browning-related genes in the subcutaneous adipose tissue (SAT) of the SL2% CUR rats but not in the SL1% CUR rats. In addition, 2% CUR dietary supplementation enhanced the serum norepinephrine levels in SL rats, with upregulated mRNA levels of β3-adrenergic receptor (β3-AR) in SAT.ConclusionDietary CUR supplementation attenuates body fat gain and metabolic disorders in SL, which might be induced by promoting browning of SAT and energy expenditure. Moreover, the benefits were more obvious in SL with 2% CUR supplementation.
| S-EPMC8557570 | biostudies-literature
Project description:The purpose of this study is to investigate the effects of probiotics combined with prebiotics (PP) supplementation on weaned rat metabolism. A metabonomic strategy employing 1H-NMR spectroscopy and multivariate data analysis was used to examine weaned rat biological responses to PP supplementation. Male Sprague-Dawley rats (post-natal day 21, PD 21) received probiotics (Lactobacillus acidophilus NCFM (L-NCFM) and Bifidobacterium lactis Bi-07 (B-LBi07), 1 : 1, 1.0 × 1011 cfu kg-1) and prebiotics (Lycium barbarum polysaccharides (LBP), Poria cocos polysaccharides (PCPs) and Lentinan, 1 : 1 : 1, 24 g kg-1) via intragastric administration for 28 consecutive days. Urine and feces were collected for analysis. Significant topographical metabolic variations were present in urine and feces. Urinary metabolites upregulated by PP treatment included alanine, N-acetylglycine, glutamine, dimethylamine, phosphorylcholine, ethylene glycol, mannitol, phenylacetylglycine and glycoate, which were related to alanine, aspartate and glutamate metabolism, and choline metabolism. Feces-derived metabolites, including caproate, valerate, butyrate, propionate, lactate, acetate, succinate, methanol, threonine and methionine, were significantly increased, which were related to short-chain fatty acid (SCFA) metabolism and TCA cycle metabolism. These results indicate that dietary PP supplementation can regulate common systemic metabolic processes, including energy metabolism, amino acid metabolism, lipid metabolism, nucleic acid metabolism, and gut microbiota-related metabolism. This study also illuminates the vital role of PP supplementation in regulating the metabolism of weaned rats.
| S-EPMC9078034 | biostudies-literature
Project description:BackgroundPrevious studies suggested that nucleotides were beneficial for liver function, lipid metabolism and so on. The present study aimed to investigate the metabolic response of dietary nucleotides supplementation in alcohol-induced liver injury rats.MethodsFive groups of male Wistar rats were used: normal control group (basal diet, equivalent distilled water), alcohol control group (basal diet, 50% alcohol (v/v)), dextrose control group (basal diet, isocaloric amount of dextrose), and 0.04% and 0.16% nucleotides groups (basal diet supplemented with 0.4 g and 1.6 g nucleotides kg(-1) respectively, 50% alcohol (v/v)). The liver injury was measured through traditional liver enzymes, expression of oxidative stress markers and histopathological examination. Ultra-performance liquid chromatography quadrupole-time-flight mass spectrometry (UPLC-Q-TOF-MS) was applied to identify liver metabolite profiles.ResultsNucleotides supplementation prevented the progression of hepatocyte steatosis. The levels of total proteins, globulin, alanine aminotransferase, aspartate aminotransferase, total cholesterol triglyceride, as well as the oxidative stress markers altered by alcohol, were improved by nucleotides supplementation. Elevated levels of liver bile acids (glycocholic acid, chenodeoxyglycocholic acid, and taurodeoxycholic acid), as well as lipids (stearic acid, palmitic acid, oleic acid, phosphatidylcholine, and lysophosphatidylethanolamine) in alcohol-treated rats were reversed by nucleotides supplementation. In addition, supplementation with nucleotides could increase the levels of amino acids, including valyl-Leucine, L-leucine, alanyl-leucine and L-phenylalanine.ConclusionThese data indicate potential biomarkers and confirm the benefit of dietary nucleotides on alcoholic liver injury.
| S-EPMC6273469 | biostudies-literature
Project description:Background and aimsMaternal diet plays a key role in preventing or contributing to the development of chronic diseases, such as obesity, allergy, and brain disorders. Supplementation of maternal diet with prebiotics has been shown to reduce the risk of food allergies and affect the intestinal permeability in offspring later in life. However, its role in modulating the development of other intestinal disorders, such as colitis, remains unknown. Therefore, we investigated the effects of prebiotic supplementation in pregnant mice on the occurrence of colitis in their offspring.Materials and methodsOffspring from mothers, who were administered prebiotic galacto-oligosaccharides and inulin during gestation or fed a control diet, were subjected to three cycles of dextran sulphate sodium (DSS) treatment to induce chronic colitis, and their intestinal function and disease activity were evaluated. Colonic remodelling, gut microbiota composition, and lipidomic and transcriptomic profiles were also assessed.ResultsDSS-treated offspring from prebiotic-fed mothers presented a higher disease score, increased weight loss, and increased faecal humidity than those from standard diet-fed mothers. DSS-treated offspring from prebiotic-fed mothers also showed increased number of colonic mucosal lymphocytes and macrophages than the control group, associated with the increased colonic concentrations of resolvin D5, protectin DX, and 14-hydroxydocosahexaenoic acid, and modulation of colonic gene expression. In addition, maternal prebiotic supplementation induced an overabundance of eight bacterial families and a decrease in the butyrate caecal concentration in DSS-treated offspring.ConclusionMaternal prebiotic exposure modified the microbiota composition and function, lipid content, and transcriptome of the colon of the offspring. These modifications did not protect against colitis, but rather sensitised the mice to colitis development.
| S-EPMC9849907 | biostudies-literature
Project description:Metabolic syndrome (MetS) is a global epidemic concern. Polyphenols are proposed as good candidates for its prevention, although their mechanisms are not fully understood. The gut microbiota seems to play a key role in polyphenol beneficial effects. Here, we assessed the effects of the citrus polyphenol hesperidin combining an untargeted metabolomics approach, which has an inherent potential to elucidate the host-microbiome interplay, with extensive anthropometric and biochemical characterizations and integrating metabolomics results with our previous 16S rRNA bacterial sequencing data. The rats were fed either a standard or an obesogenic cafeteria diet (CAF) for 17 weeks. After nine weeks, rats were supplemented with vehicle; low- (H1), or high- (H2) hesperidin doses. CAF animals developed MetS features. Hesperidin supplementation in CAF rats decreased the total cholesterol, LDL-C, and free fatty acids. The highest hesperidin dose also ameliorated blood pressure, insulin sensitivity, and decreased markers of arterial stiffness and inflammation. Metabolomics revealed an improvement of the lipidomic profile, decreases in circulating amino acids, and lower excretions of inflammation- and oxidative stress-related metabolites. Bacteroidaceae increases in the CAF-H2 group paralleled higher excretions of microbial-derived metabolites. Overall, our results provide detailed insights into the molecular effects of hesperidin on MetS and suggest that it is a promising prebiotic for the treatment of MetS and related conditions.
| S-EPMC7023145 | biostudies-literature
Project description:BackgroundPDE4 cyclic nucleotide phosphodiesterases regulate 3', 5' cAMP abundance in the CNS and thereby regulate PKA activity and phosphorylation of CREB, which has been implicated in learning and memory, depression and other functions. The PDE4 isoform PDE4B1 also interacts with the DISC1 protein, implicated in neural development and behavioral disorders. The cellular functions of PDE4B1 have been investigated extensively, but its function(s) in the intact organism remained unexplored.ResultsTo specifically disrupt PDE4B1, we developed mice that express a PDE4B1-D564A transgene in the hippocampus and forebrain. The transgenic mice showed enhanced phosphorylation of CREB and ERK1/2 in hippocampus. Hippocampal neurogenesis was increased in the transgenic mice. Hippocampal electrophysiological studies showed increased baseline synaptic transmission and enhanced LTP in male transgenic mice. Behaviorally, male transgenic mice showed increased activity in prolonged open field testing, but neither male nor female transgenic mice showed detectable anxiety-like behavior or antidepressant effects in the elevated plus-maze, tail-suspension or forced-swim tests. Neither sex showed any significant differences in associative fear conditioning or showed any demonstrable abnormalities in pre-pulse inhibition.ConclusionsThese data support the use of an isoform-selective approach to the study of PDE4B1 function in the CNS and suggest a probable role of PDE4B1 in synaptic plasticity and behavior. They also provide additional rationale and a refined approach to the development of small-molecule PDE4B1-selective inhibitors, which have potential functions in disorders of cognition, memory, mood and affect.
| S-EPMC5712142 | biostudies-literature