Genetically proxied gut microbiota, gut metabolites with risk of epilepsy and the subtypes: A bi-directional Mendelian randomization study

Frontiers in Molecular Neuroscience, Journal Year: 2022, Volume and Issue: 15

Published: Nov. 3, 2022

An increasing number of observational studies have revealed an association among the gut microbiota, metabolites, and epilepsy. However, this is easily influenced by confounders such as diet, causality remains obscure. Aiming to explore causal relationship ascertain specific microbe taxa for epilepsy, we conducted a bi-directional Mendelian randomization (MR) study based on genome-wide (GWAS) data epilepsy from International League Against Epilepsy, with microbiota GWAS results MiBioGen, summary-level microbiota-dependent metabolites trimethylamine N-oxide its predecessors. Nine phyla, 15 classes, 19 orders, 30 families, 96 genera were analyzed. A suggestive host-genetic-driven increase in family Veillonellaceae higher risk childhood absence (odds ratio [OR]: 1.033, confidential interval [CI]: 1.015-1.051, P IVW = 0.0003), class Melainabacteria lower generalized tonic-clonic seizures (OR 0.986, CI 0.979-0.994, 0.0002), Betaproteobacteria 0.958, 0.937-0.979, 0.0001), order Burkholderiales 0.960, 0.937-0.984, 0.0010) juvenile myoclonic identified after multiple-testing correction. Our sensitivity analysis no evidence pleiotropy, reverse causality, weak instrument bias, or heterogeneity. This first MR potential Four features (two levels, one level, level) interventional targets patients seizures, Previous associations numerous may had been interfered confounders. More rigorous needed

Language: Английский

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The contribution of maternal oral, vaginal, and gut microbiota to the developing offspring gut

Scientific Reports, Journal Year: 2023, Volume and Issue: 13(1)

Published: Aug. 22, 2023

Abstract There is limited understanding of how the microbiota colonizing various maternal tissues contribute to development neonatal gut (GM). To determine contribution microbiotic sites offspring in upper and lower gastrointestinal tract (GIT) during early life, litters mice were sacrificed at 7, 9, 10, 11, 12, 14, 21 days age, fecal ileal samples collected. Dams euthanized alongside their pups, oral, vaginal, ileal, This was done parallel using with either a low-richness or high-richness assess consistency findings across multiple microbial compositions. Samples analyzed 16S rRNA amplicon sequencing. The compositional similarity between pup dam used each source composition neonate timepoint. As expected, feces increased significantly over time. During earlier time-points however, microbiotas closer oral than other sites. Prominent taxa contributed by GM supplier-dependent included Lactobacillus spp., Streptococcus member Pasteurellaceae family. These align reported infant microbiotas, highlighting translatability mouse models this regard, as well dynamic nature life.

Language: Английский

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Enhanced Antioxidative Capacity Transfer between Sow and Fetus via the Gut–Placenta Axis with Dietary Selenium Yeast and Glycerol Monolaurate Supplementation during Pregnancy

Antioxidants, Journal Year: 2024, Volume and Issue: 13(2), P. 141 - 141

Published: Jan. 23, 2024

This study aims to investigate the impact of dietary supplementation with selenium yeast (SeY) and glycerol monolaurate (GML) on transfer antioxidative capacity between mother fetus during pregnancy its underlying mechanisms. A total 160 sows similar body weight parity 3–6 were randomly uniformly allocated four groups (n = 40) as follows: CON group, SeY GML SG (SeY + GML) group. Animal feeding started from 85th day gestation continued delivery. The resulted in increased placental reduced lipopolysaccharide (LPS) levels sow plasma, tissues, piglet plasma. Furthermore, redox balance inflammatory markers exhibited significant improvements plasma fed either or GML, well their offspring. Moreover, addition activated Nrf2 signaling pathway, while downregulating expression pro-inflammatory genes proteins associated pathways (MAPK NF-κB). Vascular angiogenesis nutrient transportation (amino acids, fatty glucose) upregulated, whereas apoptosis within placenta downregulated GML. integrity intestinal barriers significantly improved, indicated by ZO-1, occludin, claudin-1, along DLA DAO treatment. abundance Christensenellaceae_R-7_group, Clostridium_sensus_stricto_1, Bacteroidota, decreasing gut microbiota metabolites LPS trimethylamine N-oxide. Correlation analysis demonstrated a negative relationship weight, oxidative stress, inflammation. In summary, enhanced maternal-fetal via gut–placenta axis through modulating composition.

Language: Английский

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Maternal gestational diabetes mellitus associates with altered gut microbiome composition and head circumference abnormalities in male offspring

Cell Host & Microbe, Journal Year: 2024, Volume and Issue: 32(7), P. 1192 - 1206.e5

Published: July 1, 2024

The impact of gestational diabetes mellitus (GDM) on maternal or infant microbiome trajectory remains poorly understood. Utilizing large-scale longitudinal fecal samples from 264 mother-baby dyads, we present the gut mothers throughout pregnancy and infants during first year life. GDM had a distinct diversity composition gestation period. leaves fingerprints infant's microbiome, which are confounded by delivery mode. Further, Clostridium species positively correlate with larger head circumference at month 12 in male offspring but not females. fetuses displays depleted gut-brain modules, including acetate synthesis I degradation glutamate II. female has higher histamine dopamine degradation. Together, our integrative analysis indicates that affects composition, is associated sexually dimorphic growth.

Language: Английский

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The 16p11.2 microdeletion influences how early-life microbiota perturbations affect hippocampal development and behavior throughout the lifespan

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 25, 2025

Neurodevelopmental disorders result from interactions between genetic predisposition and environmental risk factors, with infancy being the most vulnerable period. We designed a longitudinal study to determine how short-term antibiotic exposure during early postnatal life impacts gut microbiome, neurodevelopment, behavior, whether these alterations were exacerbated by neurodevelopmental disorder-associated 16p11.2 microdeletion (16pDel) mutation. The cephalosporin antibiotic, cefdinir, broadly altered microbiome acutely, persistent reductions in several Lachnospiraceae genera despite overall recovery. These preceded long-term behavioral changes, including reduced juvenile sociability, compromised assessment, deficits associative learning. Remarkably, only cefdinir-exposed 16pDel mice had changes hippocampal stem cell proliferation, subsequent adolescent numbers, gene expression compared other groups, demonstrating that can modulate effects of early-life on neurodevelopment. may be mediated gastrointestinal disturbances, as males increased intestinal permeability shifted metabolite profiles arginine biosynthesis glycerophospholipid metabolism. Taken together, this highlights microbial affect behavior reveals influences antibiotic-induced development. Further, insights identify metabolic mechanisms potential targets for intervention raise concerns regarding use infancy.

Language: Английский

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