Absence of Bacteria Permits Fungal Gut-To-Brain Translocation and Invasion in Germfree Mice but Ageing Alone Does Not Drive Pathobiont Expansion in Conventionally Raised Mice.

Age-associated changes in the structure of the intestinal microbiome and in its interaction with the brain via the gut-brain axis are increasingly being implicated in neurological and neurodegenerative diseases. Intestinal microbial dysbiosis and translocation of microbes and microbial products including fungal species into the brain have been implicated in the development of dementias such as Alzheimer's disease. Using germ-free mice, we investigated if the fungal gut commensal, , an opportunistic pathogen in humans, can traverse the gastrointestinal barrier and disseminate to brain tissue and whether ageing impacts on the gut mycobiome as a pre-disposing factor in fungal brain infection.

The Proteome of Extracellular Vesicles Produced by the Human Gut Bacteria Bacteroides thetaiotaomicron Is Influenced by Environmental and Host-Derived Factors.

Bacterial extracellular vesicles (BEVs) released from both Gram-negative and Gram-positive bacteria provide an effective means of communication and trafficking of cell signaling molecules. In the gastrointestinal tract (GIT) BEVs produced by members of the intestinal microbiota can impact host health by mediating microbe-host cell interactions. A major unresolved question, however, is what factors influence the composition of BEV proteins and whether the host influences protein packaging into BEVs and secretion into the GIT.

The role of the mucin-glycan foraging in the communication between the gut and the brain.

is a prevalent member of the human gut microbiota, which is over-represented in inflammatory bowel disease and neurological disorders. We previously showed that the ability of to forage on mucins is strain-dependent and associated with sialic acid metabolism. Here, we showed that mice monocolonized with ATCC 29149 (-mice) display changes in major sialic acid derivatives in their cecum content, blood, and brain, which is accompanied by a significant decrease in the percentage of sialylated residues in intestinal mucins relative to germ-free (GF) mice.

Regulation of Enteroendocrine Cell Networks by the Major Human Gut Symbiont .

Gut microbes have critical roles in maintaining host physiology, but their effects on epithelial chemosensory enteroendocrine cells (EEC) remain unclear. We investigated the role that the ubiquitous commensal gut bacterium (Bt) and its major fermentation products, acetate, propionate, and succinate (APS) have in shaping EEC networks in the murine gastrointestinal tract (GIT). The distribution and numbers of EEC populations were assessed in tissues along the GIT by fluorescent immunohistochemistry in specific pathogen free (SPF), germfree (GF) mice, GF mice conventionalized by Bt or (Lr), and GF mice administered APS.

Human resident gut microbe regulates colonic neuronal innervation and neurogenic function.

Background And Aims: As the importance of gut-brain interactions increases, understanding how specific gut microbes interact with the enteric nervous system (ENS), which is the first point of neuronal exposure becomes critical. Our aim was to understand how the dominant human gut bacterium (Bt) regulates anatomical and functional characteristics of the ENS.

Methods: Neuronal cell populations, as well as enteroendocrine cells, were assessed in proximal colonic sections using fluorescent immunohistochemistry in specific pathogen-free (SPF), germ-free (GF) and Bt conventionalized-germ-free mice (Bt-CONV).

Intestinal Microbiome-Macrophage Crosstalk Contributes to Cholestatic Liver Disease by Promoting Intestinal Permeability in Mice.

Background And Aims: Mounting evidence supports an association between cholestatic liver disease and changes in the composition of the microbiome. Still, the role of the microbiome in the pathogenesis of this condition remains largely undefined.

Approach And Results: To address this, we have used two experimental models, administering alpha-naphtylisocyanate or feeding a 0.

IL-6 Signaling Regulates Small Intestinal Crypt Homeostasis.

Gut homeostasis is a tightly regulated process requiring finely tuned complex interactions between different cell types, growth factors, or cytokines and their receptors. Previous work has implicated a role for IL-6 and mucosal immune cells in intestinal regeneration following injury and in promoting inflammation and cancer. We hypothesized that IL-6 signaling could also modulate crypt homeostasis.

Selenium supplementation has beneficial and detrimental effects on immunity to influenza vaccine in older adults.

Background & Aims: Mortality resulting from influenza (flu) virus infections occurs primarily in the elderly through declining immunity. Studies in mice have suggested beneficial effects of selenium (Se) supplementation on immunity to flu but similar evidence is lacking in humans. A dietary intervention study was therefore designed to test the effects of Se-supplementation on a variety of parameters of anti-flu immunity in healthy subjects aged 50-64 years.

Single-cell gene expression analysis reveals genetic associations masked in whole-tissue experiments.

Gene expression in multiple individual cells from a tissue or culture sample varies according to cell-cycle, genetic, epigenetic and stochastic differences between the cells. However, single-cell differences have been largely neglected in the analysis of the functional consequences of genetic variation. Here we measure the expression of 92 genes affected by Wnt signaling in 1,440 single cells from 15 individuals to associate single-nucleotide polymorphisms (SNPs) with gene-expression phenotypes, while accounting for stochastic and cell-cycle differences between cells.

Methods for qPCR gene expression profiling applied to 1440 lymphoblastoid single cells.

The stochastic nature of generating eukaryotic transcripts challenges conventional methods for obtaining and analyzing single-cell gene expression data. In order to address the inherent noise, detailed methods are described on how to collect data on multiple genes in a large number of single cells using microfluidic arrays. As part of a study exploring the effect of genotype on Wnt pathway activation, data were collected for 96 qPCR assays on 1440 lymphoblastoid cells.

Effects of selenium supplementation on selenoprotein gene expression and response to influenza vaccine challenge: a randomised controlled trial.

Background: The uncertainty surrounding dietary requirements for selenium (Se) is partly due to limitations in biomarkers of Se status that are related to health outcomes. In this study we determined the effect of different doses and forms of Se on gene expression of selenoprotein S (SEPS1), selenoprotein W (SEPW1) and selenoprotein R (SEPR), and responses to an immune function challenge, influenza vaccine, were measured in order to identify functional markers of Se status.

Methods And Findings: A 12 week human dietary intervention study was undertaken in 119 volunteers who received placebo, 50, 100 or 200 µg/day Se-enriched yeast (Se-yeast) or meals containing unenriched or Se-enriched onions (50 µg/day).

Establishing optimal selenium status: results of a randomized, double-blind, placebo-controlled trial.

Background: Dietary recommendations for selenium differ between countries, mainly because of uncertainties over the definition of optimal selenium status.

Objective: The objective was to examine the dose-response relations for different forms of selenium.

Design: A randomized, double-blind, placebo-controlled dietary intervention was carried out in 119 healthy men and women aged 50-64 y living in the United Kingdom.

Se-methylselenocysteine alters collagen gene and protein expression in human prostate cells.

The anti-cancer activity of selenium is dose-dependent and species-specific but the mechanism is unclear. Se-methylselenocysteine (MSC), found in selenium-enriched alliums, is one of the most potent forms. We exposed two human prostate cell lines (LNCaP clone FGC and PNT1A) to nutritionally relevant doses of MSC and selenite, ranging from deficient to the equivalent of selenium supplementation in humans.

Effects of MEK1 and PI3K inhibitors on allyl-, benzyl- and phenylethyl-isothiocyanate-induced G2/M arrest and cell death in Caco-2 cells.

Isothiocyanates (ITCs) are potentially important cancer chemopreventive compounds found in cruciferous vegetables. In this study, three ITCs: allyl ITC, benzyl ITC and phenylethyl ITC, induced DNA cell-cycle changes and cell death in undifferentiated Caco-2 cells and their roles in PI3K/Akt and MEK/ERK signaling pathways have been investigated. Flow cytometric analysis was used to measure cell-cycle distribution, expression of mitotic marker (phosphorylated H3 histone), mitochondrial transmembrane potential for the determination of ITC-induced apoptosis measured by Annexin V-FITC staining and metabolic conversion of fluorescein diacetate, and quantification of sub-G1 population.

Ecotypic differentiation and phenotypic plasticity in reproductive traits of Armadillidium vulgare (Isopoda: Oniscidea).

Armadillidium vulgare differed in growth and survivorship on two field sites. Growth rates were higher at a site with consistently higher quality food than at the other site where less high-quality food was produced and which was less predictably accessible. Survivorship was higher at the second site where temperature fluctuations were consistently smaller.

The feruloyl esterase system of Talaromyces stipitatus: production of three discrete feruloyl esterases, including a novel enzyme, TsFaeC, with a broad substrate specificity.

Several extracellular feruloyl esterases were produced by the mesophilic fungus Talaromyces stipitatus when grown on selective carbon sources in liquid media. Type-A and Type-B feruloyl esterases, as defined by their substrate specificity against methyl hydroxycinnamates, were produced during growth on wheat bran and sugar beet pulp, respectively. In addition, Tal.