Peripherally Restricted Activation of Opioid Receptors Influences Anxiety-Related Behaviour and Alters Brain Gene Expression in a Sex-Specific Manner.

Although effects of stress-induced anxiety on the gastrointestinal tract and enteric nervous system (ENS) are well studied, how ENS dysfunction impacts behaviour is not well understood. We investigated whether ENS modulation alters anxiety-related behaviour in rats. We used loperamide, a potent μ-opioid receptor agonist that does not cross the blood-brain barrier, to manipulate ENS function and assess changes in behaviour, gut and brain gene expression, and microbiota profile.

Novel insights into mechanisms of inhibition of colonic motility by loperamide.

Background: It is well known that opiates slow gastrointestinal (GI) transit, via suppression of enteric cholinergic neurotransmission throughout the GI tract, particularly the large intestine where constipation is commonly induced. It is not clear whether there is uniform suppression of enteric neurotransmission and colonic motility across the full length of the colon. Here, we investigated whether regional changes in colonic motility occur using the peripherally-restricted mu opioid agonist, loperamide to inhibit colonic motor complexes (CMCs) in isolated mouse colon.

Anxiety-like Behavior in Female Sprague Dawley Rats Associated with Cecal Clostridiales.

The relationship between the microbiota profile and exposure to stress is not well understood. Therefore, we used a rat model of unpredictable chronic mild stress (UCMS) to investigate this relationship. Depressive-like behaviors were measured in Female Sprague Dawley rats using the sucrose preference test and the Porsolt swim test.

A Diet Enriched with HN001 and Milk Fat Globule Membrane Alters the Gut Microbiota and Decreases Amygdala GABA a Receptor Expression in Stress-Sensitive Rats.

Brain signalling pathways involved in subclinical anxiety and depressed mood can be modulated via the gut brain axis (GBA), providing the potential for diet and dietary components to affect mood. We investigated behavioural, physiological and gut microbiome responses to the strain HN001 (LactoB HN001™), which has been shown to reduce postpartum anxiety and depression, and a milk fat globule membrane-enriched product, Lipid 70 (Surestart MFGM Lipid 70), which has been implicated in memory in stress-susceptible Wistar Kyoto rats. We examined behaviour in the open field, elevated plus maze and novel object recognition tests in conjunction with the expression of host genes in neuro-signalling pathways, and we also assessed brain lipidomics.

Slowed gastrointestinal transit is associated with an altered caecal microbiota in an aged rat model.

Gastrointestinal (GI) motility is largely dependent upon activity within the enteric nervous system (ENS) and is an important part of the digestive process. Dysfunction of the ENS can impair GI motility as is seen in the case of constipation where gut transit time is prolonged. Animal models mimicking symptoms of constipation have been developed by way of pharmacological manipulations.

Generation and identification of kokumi compounds and their validation by taste-receptor assay: An example with dry-cured lamb meat.

Kokumi tastants are small γ-glutamyl peptides (GGP) that enhance flavour in foods. We sought to generate GGP from the meat crusts of dry-cured lamb, an underutilised protein resource, identify these using mass spectrometry, and validate their functional activity using a kokumi-calcium sensing receptor (CaSR) assay. The water-soluble extract (WSE) of meat crust was hydrolysed by protease A (PA) and treated with glutaminase (GA).

The Microbiome-Gut-Brain Axis and Resilience to Developing Anxiety or Depression under Stress.

Episodes of depression and anxiety commonly follow the experience of stress, however not everyone who experiences stress develops a mood disorder. Individuals who are able to experience stress without a negative emotional effect are considered stress resilient. Stress-resilience (and its counterpart stress-susceptibility) are influenced by several psychological and biological factors, including the microbiome-gut-brain axis.

Microbial signalling in colonic motility.

Sensory nerve endings within the wall of the gastrointestinal (GI) tract may respond to bacterial signalling, providing the basis for key biological processes that underlie intestinal motility and microbial homeostasis. Enteric neurons and smooth muscle cells are well known to express an array of receptors, including G-protein coupled receptors and ligand-gated ion channels, that can sense chemical ligands and other bacterially-derived substances. These include short chain fatty acids, secondary bile acids and lipopolysaccharide.

G Protein-Coupled Receptors in Taste Physiology and Pharmacology.

Heterotrimeric G protein-coupled receptors (GPCRs) comprise the largest receptor family in mammals and are responsible for the regulation of most physiological functions. Besides mediating the sensory modalities of olfaction and vision, GPCRs also transduce signals for three basic taste qualities of sweet, umami (savory taste), and bitter, as well as the flavor sensation kokumi. Taste GPCRs reside in specialised taste receptor cells (TRCs) within taste buds.

Goat milk increases gastric emptying and alters caecal short chain fatty acid profile compared with cow milk in healthy rats.

Goat and cow milk share similar protein and lipid content, yet goat milk forms softer curds during stomach digestion. This has been assumed to hasten gastric emptying (GE) on consumption of goat milk compared with cow milk, although there is no direct evidence for this. We hypothesised that goat milk would increase GE and gastrointestinal transit compared with cow milk and alter short-chain fatty acid (SCFA) profiles.

The Role of the Gut Microbiota in Dietary Interventions for Depression and Anxiety.

There is emerging evidence that an unhealthy dietary pattern may increase the risk of developing depression or anxiety, whereas a healthy dietary pattern may decrease it. This nascent research suggests that dietary interventions could help prevent, or be an alternative or adjunct therapy for, depression and anxiety. The relation, however, is complex, affected by many confounding variables, and is also likely to be bidirectional, with dietary choices being affected by stress and depression.

Differences in peptide generation following in vitro gastrointestinal digestion of yogurt and milk from cow, sheep and goat.

Fermentation of milk is commonly used throughout the world to produce a variety of foods with different health benefits. We hypothesised that due to differences in physicochemical properties and protein sequences among milk from different species and their fermented yogurt samples, their protein digestion and resulting peptide profiles would differ. Cow, goat and sheep milk and yogurt were compared at designated timepoints throughout in vitro gastric and intestinal digestion for differences in peptide profiles and peptide bioactivities.

Short communication: Processed bovine colostrum milk protein concentrate increases epithelial barrier integrity of Caco-2 cell layers.

Colostrum plays an important role in initiating the development of the intestinal barrier in newborn mammals. Given its bioactivity, there is much interest in the potential use of bovine colostrum to improve human gastrointestinal health throughout the life span. There is evidence that bovine colostrum is effective at improving small intestinal barrier integrity and some indication that it may alter colonic motility.

Metabolome and microbiome profiling of a stress-sensitive rat model of gut-brain axis dysfunction.

Stress negatively impacts gut and brain health. Individual differences in response to stress have been linked to genetic and environmental factors and more recently, a role for the gut microbiota in the regulation of stress-related changes has been demonstrated. However, the mechanisms by which these factors influence each other are poorly understood, and there are currently no established robust biomarkers of stress susceptibility.

Cryo-EM structures of the pore-forming A subunit from the Yersinia entomophaga ABC toxin.

ABC toxins are pore-forming virulence factors produced by pathogenic bacteria. YenTcA is the pore-forming and membrane binding A subunit of the ABC toxin YenTc, produced by the insect pathogen Yersinia entomophaga. Here we present cryo-EM structures of YenTcA, purified from the native source.

The Effects of Unfermented and Fermented Cow and Sheep Milk on the Gut Microbiota.

A variety of fermented foods have been linked to improved human health, but their impacts on the gut microbiome have not been well characterized. Dairy products are one of the most popular fermented foods and are commonly consumed worldwide. One area we currently lack data on is how the process of fermentation changes the gut microbiota upon digestion.

Meucin-49, a multifunctional scorpion venom peptide with bactericidal synergy with neurotoxins.

Besides key roles in prey capture and predator defense, scorpion venom also functions as internal immune agents protecting the venom gland from infection and external immune agents cleaning saprophytic microbes from their own body surfaces. However, antimicrobials (typically antimicrobial peptides, AMPs) in the venom often exist in low abundance that might exclude their immune role alone, leaving an open question with regard to their in vivo biological function. Here, we report the bactericidal activity of seven peptides isolated from the scorpion Mesobuthus eupeus venom, including one classical α-helical AMP and five ion channel-targeted neurotoxins.

Gastric Emptying and Gastrointestinal Transit Compared among Native and Hydrolyzed Whey and Casein Milk Proteins in an Aged Rat Model.

Little is known about how milk proteins affect gastrointestinal (GI) transit, particularly for the elderly, in whom digestion has been observed to be slowed. We tested the hypothesis that GI transit is faster for whey than for casein and that this effect is accentuated with hydrolysates, similar to soy. Adult male rats (18 months old) were fed native whey or casein, hydrolyzed whey (WPH) or casein (CPH), hydrolyzed blend (HB; 60% whey:40% casein), or hydrolyzed soy for 14 days then treated with loperamide, prucalopride, or vehicle-control for 7 days.

Promotility Action of the Probiotic HN019 Extract Compared with Prucalopride in Isolated Rat Large Intestine.

Attention is increasingly being focussed on probiotics as potential agents to restore or improve gastrointestinal (GI) transit. Determining mechanism of action would support robust health claims. The probiotic bacterium HN019 reduces transit time, but its mechanisms of action and effects on motility patterns are poorly understood.

Influence of Bovine Whey Protein Concentrate and Hydrolysate Preparation Methods on Motility in the Isolated Rat Distal Colon.

Whey protein concentrate (WPC) and hydrolysate (WPH) are protein ingredients used in sports, medical and pediatric formulations. Concentration and hydrolysis methods vary for whey sourced from cheese and casein co-products. The purpose of this research was to investigate the influence of whey processing methods on in vitro gastrointestinal (GI) health indicators for colonic motility, epithelial barrier integrity and immune modulation.

Towards an understanding of the structural basis for insect olfaction by odorant receptors.

Insects have co-opted a unique family of seven transmembrane proteins for odour sensing. Odorant receptors are believed to have evolved from gustatory receptors somewhere at the base of the Hexapoda and have expanded substantially to become the dominant class of odour recognition elements within the Insecta. These odorant receptors comprise an obligate co-receptor, Orco, and one of a family of highly divergent odorant "tuning" receptors.

BK channels regulate sinoatrial node firing rate and cardiac pacing in vivo.

Large-conductance Ca(2+)- and voltage-activated K(+) (BK) channels play prominent roles in shaping muscle and neuronal excitability. In the cardiovascular system, BK channels promote vascular relaxation and protect against ischemic injury. Recently, inhibition of BK channels has been shown to lower heart rate in intact rodents and isolated hearts, suggesting a novel role in heart function.

hERG ion channel pharmacology: cell membrane liposomes in porous-supported lipid bilayers compared with whole-cell patch-clamping.

The purpose of this study was to obtain functional hERG ion channel protein for use in a non-cell-based ion channel assay. hERG was expressed in Sf9 insect cells. Attempts to solubilise the hERG protein from Sf9 insect cell membranes using non-ionic detergents (NP40 and DDM) were not successful.

Molecular divergence of two orthologous scorpion toxins affecting potassium channels.

Alpha-KTxs are a diverse group of scorpion short-chain peptide toxins that affect animal potassium channels. We report the biochemical purification, gene cloning, and functional characterization of a new α-KTx named MeuTx3B, from venom of the scorpion Mesobuthus eupeus. MeuTx3B is an orthologue of BmTx3B/Martentoxin (α-KTx16 subfamily) from Mesobuthus martensii that differs by three amino acid substitutions.

Mechanism of action of lolitrem B, a fungal endophyte derived toxin that inhibits BK large conductance Ca²+-activated K+ channels.

The aim of this study was to compare the mode of action of the commonly used BK inhibitor paxilline with that of the more recently discovered lolitrem B. Similarities and differences in characteristics of inhibition between the two compounds were investigated. We have previously shown that lolitrem B does not affect the BK channel G-V, in contrast to the rightward shift produced by paxilline.